Transcript for:
Physio: CNS and Neuro Topics Overview (18)

e all right I think I'm live let me know if you can uh hear me okay let me get started here in just a few minutes all right thank you periz I hope I'm saying correctly I don't know if I am or not but appreciate it know the forecast says it's going to storm I'm doubtful it's been way too dry around here I don't know if Jacksonville is in the same boat or not but let's play it for the the rain pray for the rains but and hopefully not the thunderstorms that will uh knock my power out my internet out but if something un tour does occur no big deal we'll we'll find we'll fix it somehow all right so by my clock I have about just about 3:00 let's go ahead and uh get started here as we're going through um okay everything it's working righto let's do this uh so this is our last section for the course which is hard to believe it's already almost over it's been very quick but don't worry if you're sad about not getting to hear my my dolls at tones anymore uh I we do have our pharmacodynamics course that will be uh starting up uh sometime later sometime in June I think oh regardless um so this is uh the start for our neurot topics um this can be a bit of a bear for people and again I was going through the lecture and I was just like boy this stuff is kind of complicated that's okay so if you have questions put the link there for the stiky board please ask frequent questions if anything I say does not make sense to you or if I was unclear about anything um but otherwise we're going to get into it let's see uh someone had a question over here someone said do individuals that are blind to creep melanopsin you know um I think a a lot of that is going to depend on the degree of blindness or unsighted or however you want to term it um because you can have a large degree of people who are legally blind quote unquote but they may still have some degree of vision so um I imagine that that would change in terms of if you had like complete and total blindness U that that would affect things like melatonin secretion and melanopsin the specific changes um to say whether or not they have any I don't know off the top of my head but I I would imagine that would certainly change um but again I don't know how much info is out there about that specific topic so yeah any let's get into our discussion of neuro which again you know melatonin is a part of the CNS so of course let's we're going to be talking about that at some point uh so here are the objectives for this specific section here uh if you've noticed I uploaded all the other PowerPoints as well so we're going to kind of go through different um you know CNS fun funs and whatnot how we're going to be integrating things like external stimuli we'll talk about Sensations we'll get through all that kind of stuff as we go through the different sections here so um if the objectives are slightly off in terms of like where I cover something I Do cover all the objectives um but this is kind of like stitching This Together from like my old neuro lectures like how the course has this all broken down so I'll hit all the objectives at some point um it just might be not quite in this PowerPoint it might be in the another one or vice versa so let's get into it so so the CNS the central nervous system here um is pretty complicated as we're going to find um you can think about it as being our body's computer and it's going to be taking a lot of inputs it's going to be generating a lot of outputs um in order to help control your body in the world and so we can see here more than a 100 billion neurons that are making up your central nervous system so hugely complicated um and you can find these connections may be varied you may find um they have maybe just like a few hundred connections with other neurons you may find like up to 200,000 it's crazy how complicated this stuff can get here um generally speaking though every neuron will have one output through a single axon here um they may Branch at a point but generally speaking have one axon that's going to be sending a signal out onto either onto a muscle or another what the case may be here um generally speaking this allows for kind of this forward facing sort of communication where you're not going to be getting signals being sent back up the axon into the cell body it's only going to go basically out um and so mainly just forward direction of transmission of that signals are going to see um I know we've talked about Action potentials previously I will touch upon that here again briefly just in response or in regards to the actual CNS function as we're going to get into it so we'll do A Brief Review as we get into that um and so we're going to be finding that the information so these are going to be the sensory inputs so these are going to be all of the afferent signals with an A so signals coming into the brain are going to be traveling from the peripheral tissues like the muscle the skin things like that um through the spinal cord through the brain stem into the cerebellum we get kind of sequence through there eventually gets to the thalamus and the thalamus is going to be an important sort of like signal integration area of the brain where we're going to be able to then send those signals to the cerebral cortex and if you notice here they're going to have the some uh smat athetic areas they may call them or smato sensory areas and this is where you're going to be getting all of those inputs to be able to tell you information like well what position is the body in are you feeling pain is it hot or cold or whatever the case may be that's all going to be getting sent up into that somato sensor area which then can communicate with other places like the motor cortex for example to cause movement to occur but this is the general flow of these afferent signals coming in from the peripheral tissues in through the spinal column to the thalamus to eventually go to those that cerebral cortex there we then have the motor parts of the nervous system so you can see the different motor areas here and we'll talk about more details on how those are going to function in the motor section later on but we'll find that these are going to be sending a lot of eer signals with an E so sending signals out to be able to initiate things like movements right so in terms of motor function we think about skeletal muscle activation certainly um but there are others as well so you could have things like smooth muscle activation which could control things like peristalsis in the GI tract or how constricted your blood vessels are um we'll also see secretion of things like your ex and endocrine glands as well so if we're telling uh the pancreas to start to secrete bicarbon to the you know the datum for example there um these are considered to be affectors because you've taken a signal in you've integrated that in the brain and now you're sending a response signal back out so these are going to be affecting things these are the affectors that's also why it's an eent signal because it's heading out from the brain okay and so we're going to find that lower regions of the brain here can allow for and we're thinking more like your brain's for example this is what we call the lizard brain so it's kind of the most um sort of primitive of the brain functions here these lower regions are going to be useful for helping to set things like automatic functions so for example things um like breathing we don't necessarily need to have conscious control of breathing but our rate of breathing our depth of breathing will change based off of these sort of responses to sensory information coming in so if you're cheemo receptors and the cred body telling you there's too much CO2 that lower portion of the brain will say oh yeah now it's time to breathe a little bit faster to be able to get that CO2 out right um higher regions of the brain once you start to get up into the cortex here um are going to be better for more deliberate action so if I'm thinking about how I'm going to be giving this lecture calling on my memories in order to be able to say the words correctly to be able to convey this information that's a lot of like higher level control of the brain through the cortex and we'll talk about how we do all that a little bit later so this integ creative function of the nervous system so this is where we're going to be basically taking in a ton of information coming from the body and then trying to integrate to figure out okay well what actually do we care about what's actually the important information that we need to be able to survive to thrive to give a lecture to listen to stay awake whatever the case may be and a lot of the information coming in like 99% of all the sensory information going into your brain is useless garbage data it's irrelevant or unimportant so for example do you feel the clothes that you're wearing right now probably not because you don't really need to feel your clothes on you in order to survive and so you will start to downplay a lot of that information the brain says well I don't care about that so don't think about it right um when you're SE seated for example you don't feel you don't think about that pressure you don't sense that pressure unless you consciously kind of bring it up right um this is allowing us to do things like drowning out sound so that way even though you're in say a chaotic environment you're able to focus on one task for example or focusing on one object in your visual field even if other things are maybe moving around and so those things that are deemed important enough that we can actually pay attention and again think about attention as being sort of a finite currency you can only pay so much because again too much sensory input is going to make things go hwire um those things that are important enough to be able to pay attention to um end up being stored as memory here so this is useful U for helping us with things like muscle memories so that way I have that kind of memory of how to move the muscles to cause a certain thing to happen so for instance if I think about how to finger a C chord on a guitar my hands kind of just naturally go to the position because I have that muscle memory from doing it so many times um a lot of that storage happens up there in the cerebral cortex okay and memory helps we can better facilitate memories due to this facilitation process here uh meaning that the more time that you can have those same set of synapses firing during the time you're making a memory the more able you are to be able to bring that back up that memory back up in order to use that at a future time so even if I don't have the feeling of guitar strings under my finger my brain can still tell my hands to go into this fingering you know the actual positions for a c chord for example um this is also where we're going to find the more like you listen to a lecture or the more that you review your notes the better you're going to be able to bring that information back up at a later time in your memories when you're taking a test for example here that's why I always record my lectures to make sure that you can always go back and hear it over and over and over again because the more that you have those same synapses being firing you're facilitating that you're going to be more easy easily able to have that memory come back up when you don't have the initial input so when you don't have the lecture available you can remember what I said about ponary function test or whatever the case may be so sort of major levels of the CNS function we're going to see here we have the spinal cord level here so this is where we're going to get a lot of signal transmission so either up the spinal cord or down you know depending on if we're having an AER or eer signal there we'll see a lot of reflex arcs happen here as well especially when it comes to um things like muscular movement or things like um whenever like say someone Wass to drop a heavy load into your hands drops a textbook into your hands and your hand just doesn't like Drop and then you drop the book you have a lot of reflexes that allow you to have instantaneous responses dep independent of signals going to the brain it'll eventually get there but you have some of these reflex arcs we'll go over a few examples of those a bit later when you get into the lower brain function the subcortical type of level So Below the cortex here this is where you're going to see a lot of subconscious activities like I mentioned before so things like regulating arterial arterial pressure breathing um we can also find in this lower level here we can see some things like emotional patterns where um things like sexual responses excitement anger some of these things are sort of automatic and we don't have a lot of control over it for example so if someone if an attractive person walks by you may get that automatic sort of response to be like oh that person's pretty cute right um so some of those emotional patterns will be handled through the lower brain uh levels there um for higher brain function or this cortical function here this is where you get a lot of memories being stored um this is where you have a lot of conscious control of movements where I can say okay I know I need to go walk you know stand up walk over to the desk or the door pull the handle down walk to my C turn the keys on drive the car to wherever blah that's all conscious control there and this is where a lot of our thought process happens as well so if we're doing things like critical thinking um problem solving doing a puzzle whatever the case may be um this is where we're going to see this happening at that cortical sort of level so what are the cells that are actually making up the both peripheral and the central nervous system as we get into it um we'll abbreviate peripheral ner system is pns but I'm not going to say that very frequently because if you say that too often too quickly it sounds like something else and that's not what we're talking about today um so the peripheral nervous system is made up of one the actual nerves themselves but a couple of neurog gla are these gal cells here uh the first of which you're going to find are the Schwan cells which who doesn't love saying Schwan that's just a fun word to say but these are useful because these help to actually form the myin sheets around these peripheral axons really really important because one these help to facilitate really quick transmission of action potentials so which we'll discuss those a bit later um these also have some FDIC ability so these can help out with things like helping to prevent infection perhaps or getting rid of um some kind of debris or toxins and things like that you will also then have your satellite cells and so if you see ganglionic gyes that's another term for these satellite cells here and these are going to be supporting the actual cell bodies of the nerves uh within the ganglia and we'll talk about ganglia where they're going to be kind of situated whether for motor function or if we're talking about like autonomic nervous system function things like that we'll get into it but at those ganglia um we're going to find the satellite cells help to provide that sort of structure provide that support there um these can also help to regulate so that sort of chemical Environ environment around these peripheral nervous system neurons here um helping make sure they are at the correct pH helping make sure they're uh the correct temperature all that kind of stuff once we get into the central nervous system we have four main types of sort of support cells these neurog Galia here um the first one of which is the Ala dender sites and these are responsible for forming the melin sheaths around the axons within the CNS so in the peripheral nervous system of those Schwan cells we talked about here theed dendrites um again these are very need necessary because they help to Pro uh provide quick transmission of action potentials along the neurons along the axons um we then have the microa so these are going to be sort of migrating around you can kind of think about these is sort of being like the immune function within the brain itself so these are able to um take things like form material things like generated materials and get rid of them essentially by working in sort of a FDIC sort of cell there almost like your macras is a little bit um then you have the astrit so these are responsible for helping to regulate the external environment of the neurons and so if you notice here if you look at these astr sites in this particular picture um you can see how it sort of forms these like little poyes these little foots that's kind of sending out projecting out that will surround things things like the capillaries are going to be in the CNS this can help to control what's getting in or out from the blood in order to regulate that environment so for example when we talk about the blood brain barrier we'll get into that more explicitly in a second here um the astrocytes are really responsible for helping to form that because um kind of think about this is kind of being like the bouncer for a club if you want to go to a fancy Club there's a bouncer there keeping the Riff Raff out people like me um that's what the astr sites are doing here they say no we want to make sure this is a pristine environment we don't want just anyone getting in here and we'll talk more about that in a second um and then you have these endal cells and these are aligning the actual ventricles within the brain and this is where you get secretion of your CSF so that's kind of setting again the stage for kind of what this internal sort of environment is um in terms of things like you know pH and regulating glucose and all that's going to be mediated through this cerebral spinal fluid so these endal cells do that and here's a table you can just kind of go through and be able to compare and contrast the cells what they're going to do again just note that the Schwan cells and the satellite cells are located within the peripheral nervous system so everything outside of the CNS and then within the actual CNS itself we're going to see the El digc sites microa Etc so kind of know generally what their function is going to be um for like testing purposes all right so I mentioned the mile and sheath being really really important here within the CNS you can see a couple of cross-sections um a tery may see being used when referring to the brain is like the gray matter versus the white matter uh my and sheets are what's generally going to be the differentiator between the two here um so the myin sheets around those axons there provide that white sort of coloration so all of those axons are going to be traveling through the spinal cord for example that we consider that to be part of the white matter and part of the brain itself will be made up of white matter usually we get into like the cortical sort of areas like the frontal cortex for example um those are going to have cell bodies that lack those myelin sheets um so they don't maybe transmit signals quite as quickly um but they are able to have their own functions here so that's where we consider it to be the gray matter of the brain itself so if you were to take someone's brain out you would see oh that looks kind of grayish so me get rid all the blood and stuff uh the asites only like I mentioned the m and sheath um are going to be necessary for helping with quick transmission of action potentials along these axons so when you have you know axons that can be traveling from the brain all the way down to your little pinky toe that that's a pretty long distance there and you want to make sure that that transmission can happen quickly um and there are cases where that can go wrong so for example if you have a condition um for example multiple sclerosis yeah I missed um that is a autoimmune condition where your own immune system is fighting and starting to strip those axons of their myelin sheaths and that can cause whole host of different neuro isues including issues like neuropathic pain the those transmission signals not working as well so patients have like movement problems all kinds of things go wrong when you don't have these myin sheets around so very important for the normal function there I mentioned the astrocytes help to control the interfacing between the blood and all the substances that are in there um and then what actually gets out and into the CSF itself um so this is the blood brain barrier and if you notice here if you look at this picture which my head's kind of covering um you can see how it forms this very nice tight barrier around um making sure to get things that we want to come in and preventing things from getting in there that don't need to be there or if we're going to be like shuttling things out of the CSF and into the blood Um this can help to for form that sort of interface there as well and so we can find here that substance can only be moved by very selective process here either through diffusion itself um or there's some other ways we can get things through so some things that are just like super lipophilic can get into the brain just fine they can kind of cross this barrier without a whole lot of uh issues there um so for example if you think about the drug th C or tetrah hydr canaban which you find in marijuana that's very lipophilic that's a pretty easy time getting across the blood brain barrier into the brain to cause you know some to be high for example here um things that can't get through just on their own lipophilicity um will have to get through in some other way so this can happen through things like transport proteins which may be necessary here um things like trans cytosis can happen for example here uh but what's also kind of neat here is we have a lot of like pump will be kind of lining this barrier where we may have things like elux pumps and so even if something does get in you can basically elux it back out and prevent it from getting into the brain itself so those are all kind of necessary processes here which help to regulate again what gets through keeping out the stuff that shouldn't be there for example um this the ability for this Blood brain barrier to work can also be changed by certain disease States so just as an example um and again this is one way that you know the body keeps the a lot of drugs different types of drugs from getting into the brain um there are cases where if you were to have inflammation of the bloodb brain barrier you can actually find that you'll start to form little gaps between the barrier and so we will have someone for example has menitis there are certain antibiotics not to get too much into the drugs but there are certain antibiotics that if we give it to someone in their blood like via IV um that they never cross over it's very difficult for get to get into the C they're not very good for treating menitis there are some drugs that when you're in a normal State like you're not having menitis um they can't get through because the gaps are too too narrow there's no other way for them to get in however if you have menitis and you're really inflamed those gaps start to open up and all of a sudden certain drugs are now able to get into the brain to able to treat that infection to help cure your patient so these things can change depending on disease States and other issues that are going on within the body itself but generally this is meant to keep stuff out that should not be there um just to give you another clinical example that had come up one time uh there is a drug that you can use if you have diarrhea it's called laramide and laramide works by acting on certain opioid receptors so opioids like think you know morphine and heroin and Fenty um you know for pain relief for example but we also know that there's opioid receptors all through the GI tract that help when it's activated slows down movement so if you have diarrhea where you're having too much movement of the GI tract you can give this drug laramide activates his opioid receptors and it slows everything down right um the reason why laramide is a drug you can just buy at the CVS on on off the shelf is because it cannot cross the blood brain barrier to act on opioid receptors that would cause you to be high or cause respiratory depression or cause addiction uh the reason why leite cannot get across is because you have these e-lux pumps in the blood brain barrier that helps keep it on the side of the blood and cannot get into the brain well there are some other drugs you could take as well that actually can help to inhibit these e-lux pumps and so I had one patient who who wanted to get high didn't really have any easy access to any other drugs and so they had read online that hey if you take this combination of two drugs one's called sadine or Tagamet which is used for like gird symptoms it's a acid reducer uh if you take that because it's going to inhibit this pump here and then you take a whole bunch of little paramid it's then able to get across and you should feel a high very similar to if you just done heroin so again you go to the store buy a bunch of this stuff you know the cashier is like oh maybe you're having some GI problem is not a big deal right uh a ton of the stuff took it all and I don't know if she had a very good high off of it but eventually she came to us um severely respiratory depress ended up having to be intubated um end up going into an arhythmic called torsades um big hot mess fortunately she lived to tell the tale um but not something I would recommend doing so at the end of the day my recommendation is always don't do drugs just try for him if he can anyway so um synapses within between neurons within the CNS here um we're going to see going to be transmitted these signals are transmitted via Action potentials and I know we've talked about that briefly um when it comes to like cardiac function we've talked about it when it comes to skeletal muscle function here now we're kind of discussing it more specifically within the CNS fortunately not a lot of that has changed and so we'll go over A Brief Review just to make sure we're all on the same page here um but as I mentioned these impulses will be sent through the axons and then usually some sort of interfacing with another neuron um so this is this inap here and so we'll find these Action potentials can be inhibited they can be facilitated through different ways uh we may see just like single signals being sent or it could be more of like a repetitive sort of impulse multiple signals coming in and again the effects on the post synaptic neuron is going to be based off of all the different inputs that are coming into it some of which are excitatory some of which are inhibitory the overall net endpoint will then dictate what that next neuron is going to do whether it's going to be excitatory inhibitory Etc um when it comes to these synapses here there's two main types there's what we call chemical synapses and then there's electrical synapses the chemicals meaning dealing with the brain's own neurotransmitters are basically and this is the top one here you're looking at when you're looking at a chemical synapse basically in these pre synaptic neurons you're going to have these little vesicles that are filled with neurotransmitters and we'll go over A Brief Review of neurotransmitters here in just a bit um once an an action potential comes along it will then cause some of these calcium channels to open up these are what we call voltage gated calcium channels because they need a change in voltage like an AC potential to open up that allows chloride to flow in or calcium I should say calcium to flow in that will then cause these vesicles to then undergo exocytosis they're going to fuse with the cell membrane and then release that neurotransmitter and then depending on what receptors are located here on the post synaptic neuron some change will happen so whether it's going to be excitatory or inhibitory we'll go over the different types of um receptors you're going to run into in just a little bit here but some change is going to happen here so you notice your neurotransmitters can excite inhibit modify the sensitivity meaning it's going to either be more or less likely to then fire later on and then some of the common neurotransmitters we're going to see here include things like acine which I know we've talked about in several different places already things like you know urinary function for example but other ones we haven't really gotten into include things like glutamate serotonin Gaba there others and I'll go over those in more detail here um again this is oneway communication so this is just going to be sending a signal this unidirectionally just heading this direction here from the Press synaptic to the post synaptic neuron not sending any signals back up okay for the electrical synapses here if you notice there's a much kind of tighter sort of interfacing here if you notice there's these little Gap Junctions here and so in this way when you have an action potential come along the that change in potential is just going to naturally kind of float through here and that's going to then cause that action potential to continue along and so because of the sort of bidirectional nature of these Gap Junctions here these pores um bidirectional transmission is possible this is not as common as the chemical uh synapses but could be useful for other purposes so looking at the synapse here if we're looking at sort of the anatomy of the neuron itself we have the Soma or the body of the neuron itself this is where most of the uh definitely organel and things like that are going to be located like the nucleus for example here uh and then if you notice there's one single axon heading out and so again usually going to be transmitting signal just in one direction through the axon to interface with then another neuron here um we'll have the dendrites which are going to be these kind of portions of the neuron here where there's going to have um different neurons and different synapses here that will be able to provide signals either excitatory or inhibitory and then depending on all the different inputs here so some are positive some are negative based of all the signals coming in it will dictate what this neuron is going to do whether it's going to cause a net excitation to say hey let me fire off an action potential or if it's a net inhibition that says like nope not going to do anything I'm just going to stay resting again depending what's going on in the body those inputs and outputs or all those different inputs may change depending on like pH in the CSF or oxygen concentration or is there glucose around lots of different things like that so I mentioned the synaptic vessels here these will contain our neurotransmitters some of which I mentioned are excitatory some are inhibitory here um you'll notice there's also a lot of mitochondria that are around and these are going to be able to provide the energy necessary the ATP necessary in order to form those neurotransmitters in the first place and so we'll talk a little bit about how those are formed and what they're made out of and things like that and then I mentioned the voltage gated calcium channels here so as that action potential comes along you'll see these calcium channels then start to open up and that causes neurotransmitter release so more calcium coming in more vesicle release that happen so the stronger sort of signal you're then going to be sending to release more vesicles to release more a transmitter to get a stronger effect whatever that may be on the post synaptic receptor there okay so so what are those receptor proteins here they can be several different things and again we'll cover this U briefly when we get into the pharmacodynamics course later because these are very frequently are drug targets these are things that medications are meant to be affecting to cause changes in things like your behavior or your mood or things like that um and so we'll have our gated ion channels these are again going to be channels that when activated by a neurotransmitter they allow for an opening to allow for movement of ions and so this will usually include either like C channels which will be letting positive ions in like sodium potassium calcium sodium is a big one um these are excitatory because as you send more positives into the cell the electric potential gets higher meaning it's more likely to cause an action potential to occur an channels are going to be mainly dealing with your negative ions and that's mostly just chloride it's a big one in the in the blood um these are inhibitory as you have more negative coming in you're going to hyperpolarize that neuron and making it more difficult for it to fire okay we'll talk about the neur transmitters that affect that more directly um the we also have these metabotropic receptors here and again if you're looking at the the picture you can see the inotropic receptors here which is just another name meaning ions can flow through them um and so once these open ions are able to flow along their concentration gradient either clide coming in or your p is like sodium coming in here and then you have what we call the metabotropic receptors and so these include things like your G proteins for example I'm not going to get so much in the weeds um on these now we'll talk more about these when we get into like pharmacodynamics for example here but they're going to be working through what we call secondary Messengers so you're going to have some signal coming in some transmitter like a neurotransmitter that will bind to a receptor and then it causes and this is what we consider the first Messenger will activate some proteins here that will be our secondary Messengers that will cause something Downstream to occur so whether it's causing the cell to become more excitable or less excitable or causing it to undergo mitosis or whatever the case may be um it can happen through these G proteins as one example of a metabotropic receptor someone did have a question that say can you re-explain the bidirectional transmission yes I can all right so normally if we were to be looking at this picture here you can see that if we have a chemical synapse here the only way you can send a signal is by releasing neurotransmitter to then activate some receptor here on the postseptic receptor and then that will cause transmission of a signal whether it's inhibit you know more uh likely to occur or less likely to occur of the case may be um that it only goes in One Direction you're meaning that there's no way for the Post synaptic uh neuron to give a signal back to the presynaptic neuron that says hey do something there just doesn't happen um so as a result of that the signals can really only go from pre depos synaptic receptors or preos synaptic neurons so it's unidirectional a unidirectional transmission here when you have an electrical uh sort of connection here what you're going to see is because the ions can flow in either direction that you could have an action potential that starts up here that transmits in One Direction but let's say you have an electrical impulse that happens say down further down on this particular neuron here if that sends an action it can then go back in the other direction so again that can be good in some cases for normal function or that could be bad in some situations so say for example um if you're sending abnormal signals or abnormal Action potentials that are not very uniform that's where you can run into things like seizures for example so we don't want seizures we want our brains to be sending ax potentials normally uh so in that case there bidirectional transmission may be normal or it could be abnormal in some as a case it may be just depends on where the stronger signal is in terms of what's going to drive the signal to go from one direction or another so hopefully I answered your question if not let me know and I can try again okay so this is the list of majority of your neurotransmitters that you're going to run into I'm not going to cover every single one of these although if you you'll recognize a few of these we've already talked about so for example in the endocrine section we talked about things like prolactin and luteinizing hormone um you know things like gastron chis I'm sure you talked about during the GI section um I'm not going to cover every single one of these I'm going to talk about the main ones that are necessary for your CNS function and we'll talk about where they come up and what they're used for how we produce it all that kind of good stuff and more detail here so if I mention one on this list doesn't mean I'm going to go into a great lot lot of detail on it meaning you probably don't need to worry so much about it for testing purposes but the ones I do have specific slides on those are the ones you definitely want to know for sure so start off with the first one aceta Coline we've talked about acine a lot when it comes to things like function of uh the bladder for example when it comes to urination we've talked about it in other places as well for things like skeletal muscle function how CTO coins necessary for helping your skeletal muscles to contract right um cocoline is made from the com combination of aceto COA plus a choline so aceto choline I had a professor in pharmacy school he refused to call it acet choline says it's acetal choline and he's just very adamant about that and I said that sounds silly I'm not going to say it that way so C theum and so it's good to know how it's formed also important to how we can metabolize it and how we can actually um get rid of it because we want to keep Balan we don't want too much acetum we want too little so what we're going to see here is that acetol esterase is the enzyme that metabolizes acetycholine so to metabolize that we can take that choline that we've now liberated and we can then recycle that back to the presynaptic neuron to then form new acetycholine the brain's pretty good about recycling neurotransmitters as best we can because it takes energy to form those so if we can instead recycle them the packag them back up for later use that's going to be a better conservation of our energy for brain function um uses for cedine in are quite varied and we're going to see here um both good for somatic transmission meaning that you'll see neurons that will be specifically um going in inating things like your skeletal muscle releasing a cing directly onto nicotinic receptors if you recall to cause the muscles to contract so you're going to be transmitting an action potential that at the very end of it is going to cause the cedolin to dump out onto the skeletal muscle that then transmits that signal to then generate an action potential within the muscle to cause your bicep to flex for example also good for things like autonomic transmission so cocoline is both used in the sympathetic nervous system which is that fight ORF flight response and also the parasympathetic nervous system your rest and digest how can it be used for both CU you're like wait a second doesn't make sense but if you look at the the parasympathetic nervous system function here we'll go over much more detail on this when we get into the autonomic PowerPoint later on so if you notice here you're going to be sending a neuron out from the CNS that will then release a cocoline onto these ganglia and say ganglia are we're then going to have a secondary signal that'll be sent so it's kind of this interfacing between the two um and if you notice aceta choline is going to be activating both nicotinic receptors at the gangal here to cause this neuron to then releases cine but if you notice in the tissues now we're going to see The muscarinic receptors come into play here and so this is where you get the majority of your rest and digest kind of effects here so for example um if you activate acolin onto MUSC receptors in the GI tract you cause increased peristalsis if you release the cocolon onto MUSC receptors in the eye it causes a pupilary constriction whole host of other effects we're going to get into those in more detail uh at a later PowerPoint so and if you're looking at the sympathetic transmission here you'll noce notice that you will be having neurons that are releasing AET cooline onto nicotinic receptors here both in places like the adrenal gland and also onto these gang that will then inate tissues and this nerves here now releases norrine so you think about norrine as being the major player for the sympathetic nervous system but really it's going to be the two working together so seeing on nicotinic receptors then causing that neuron to release norrine onto adrenergic receptors or your Alpha Beta receptors we'll get into those in a second um so two main receptor types nicotinic and the muskic so keep those two in mind because um they'll have very different functions especially when we get into the autonomic lectures there uh someone had a question here says are metabotropic receptors responsible for the pituitary to release hormones after receiving hormones from the hypothalamus um I don't know if they specifically work on certain metabotropic receptors I'd have to go in look to see like each individual one um it stands to reason probably you're going to find that a lot of different um functions happen through these metabotropic receptors not just when it comes to normal body function but also through like drugs too when we are introducing uh medications that can affect the body um so educated guess is yes there's probably some metabotropic receptors are there probably some ion gated channels too yeah likely probably going to be mixture of both depending on which specific hormones um the hypothalamus is telling the pituitary to release so and then someone a question can you explain the somatic and autonomic transmission again yes um so let me switch back over so when we say somatic system think Soma I think body I think it's Greek for body um it means your body movement so the somatic system is going to be mostly your skeletal muscle we're talking about that cause me to get up and you know punch of punching bag or whatever I'm doing that's going to be through the somatic transmission so that's going to be usually um under voluntary control so that way my body is able to get up and go walk and go down the stairs whatever the case may be so any type of body movement think skeletal muscle think Soma think your body movement that's where that's going to be necessary the autonomic sounds almost like automatic is an involuntary system and so as an involuntary system here your brain's going to be controlling this through responses to things like hey did I just eat a big meal or you know what's my pH looking like or hey is a bear just like jumped out at me and I need to run away from this so these are automatic responses that you're going to see that will allow for changes in organ function to allow for those responses so in the case of I just ate a big meal you'll be activating that sympath parasympathetic nervous system that then allows your changes to occur within the GI tract to better digest your food right versus if I'm in a fight ORF flight response you'll see a different type type of signal that are be happening through the sympathetic nerves that will cause changes in blood flow so that way I don't send as much blood flow to my uh GI tract but I send it to the muscles instead and liberate glucose from the liver so that way I have energy to run things like that so hopefully that that clears that up all right next up we have nor epinephrine which is I mentioned a big player in the sympathetic nervous system um we're also going to see that norepinephrine and epinephrine which is produced in the adrenal medula um have very similar functions slightly different flavors but when it comes to CNS function here norpine nephrine is the big player norpine nephrine in the adrenal glands will get converted into epinephrine that's why they have so much similarity in terms of their function anyway where do we get this from this is coming from our diet basically we have certain amino acids like tyrosine and tyramine to a degree um that is able to then be converted in the CNS over into norepinephrine and you can kind of see the different steps here so for example if I have tyrosine this get converted into dopamine actually or dopa which is like the precursor uh levadopa into dopamine so dopamine is another big one we're going to talk about in a second here and then dopam get converted over into Norine ephrine so that's why there's a lot of these are kind of cousins of each other because there's this sort of lineage where one gets converted into another one um if you recall we talked about norpine phrine epinephrine dopamine they F into that category what we call a catac colomine so it's a chemical classification for these um that's important when we talked about the metabolism here in just a second um interestingly you can find there's certain types of foods that are really high in precursors to norepinephrine so for example if you were to eat um some kind of aged meat or cheese or maybe like a fava Bean for example those have really high amounts of tyrosine which can get converted into a bunch of norpine phrine which can actually lead to health problems um so especially if you're taking a certain type of medication you can finally get way too much norpine Effron being produced if you consume these meals and then that can then cause things like really high blood pressure can cause um hypothermia all kinds of bad problems there so how do we metabolize norrine to make sure we don't have too much of it and so there's two main enzymes that are responsible here one of which is catacol methyl transferase or comt you can see there and then there is another one which if you're familiar with drugs for depression monoamine oxidase so monoamine oxidase is able along with comt to be able to metabolize the norrine into inactive metabolites if you were familiar like I mentioned with depression medications the first class of meds that we had that treated depression were called monoamine oxidase Inhibitors cuz what we found was is if you block this enzyme you actually end up raising up levels of other monoamines in the brain like nor nephrine but a big one is serotonin and so by decreasing your metabolis and serotonin they notice these patients moods are impr improved and so we said oh this must be it that's why serotonin is you the feel good feel you good good attitude good you know good feeling type of neurotransmitter it's not the full story but that's where we started and then from then on we have more selective medications here but so if you ever hear maois that's what they're referring to as an inhibitor of that monoamine oxidase here so what does norrine do in the brain we're going to see that one it's going to be largely responsible for the effects of the sympathetic nervous system so it's generally going to be excitatory and then within the brain itself the brain stem and the hypothalamus they're going to find that releasing norrine helps to increase levels of wakefulness so having more this norrine around helps to maintain levels of arousal so that way patients are not going to be falling asleep at their computers like some of you might be doing right now I'm sure if I made a big loud noise I could like jolt some of you awake and that jolt could be as a result of releasing norpine phrine onto the brain stem that says hey wake up like uh my wife today she was taking a nap and so I uh said hey um what time is pickup for for Phoebe she goes uh 1250 I say it's 12:45 right now she went from very much asleep to very much awake and part of that is that kind of fight ORF flight response and part of that is going to be mediated through norp andron don't worry my kid got picked up they weren't just ring the streets on their own anyway The receptors that these are going to hit are going to be the adrenergic receptors think norrine think epinephrine think adrenaline adrenergic receptors that's where that name comes from so these are going to be activ activating your Alpha receptors so alpha 1 and two are the primary ones and then your beta receptors beta 1 and two there's a beta 3 clinically speaking it doesn't come up all that often so we're not really going to be too worried about that but for example if I were to activate beta 1 receptors on the heart you'd expect to see an increase in heart rate by activate Alpha 1 receptors on the blood vessels you'd expect to see an increase in blood pressure all this is through these adrc receptors being activated by norrine similarly if I wanted to give something to reduce your heart rate I could give a a blocker and so that's an antagonist that will help to reduce your heart rate if that is necessary for your cardiovascular function there next we have dopamine dopamine is one of my favorite neurotransmitters just because it is responsible for the reward pathway that we'll see here in just a second dopamine has a very similar formation very similar synthesis to what I talked about with norepinephrine and in fact dopamine in certain neurons gets converted into norp andrine so they kind of do similar functions there in terms of being able to actually be synthesized um similarly they get metabolized by the same same enzymes so cacom methyl transferase and monom oxidase similarly will metabolize dopamine that make sure we have normal levels there um so function here we're going to see it largely gets secreted from an area of the brain called the substantia and what we're going to find here is we actually have three main uh Pathways here we're going to see here first of which is the Nigro strial pathway this is super important for helping with movement so especially with like more more complex movement patterns like getting up and going and driving a car whatever the case may be um that is to that Nigo strial pathway and in fact if you have patients who have low amounts of dopamine in that pathway it's called Parkinson's disease and if you don't have enough dopamine you cannot initiate movement so one of the problems you run into with Parkinson's patients is that in really severe cases they can be catatonic basically just completely locked up not able to initiate really many movements at all and so one of the things we can do for them is actually give them a precursor to doping called levadopa and that's actually how we treat Parkinson's that levadopa gets converted into dopamine and then our patients will start to move again so really important we'll talk much more about that in the motor section uh coming up in a bit um the means of cortical pathway I mentioned this is uh useful for the reward pathway so if you do something rewarding like getting an A on the test or um you know having a big juicy hamburger if you love hamburgers if you have sex or if you gamble and you win big or if you do heroin all that stuff causes dopamine to dump out into this music cortical pathway it tells your brain that that was amazing I would like to do that over and over and over again and so that's also how you get into addiction and so because addiction can be such a big component of my work both in Pharmacy and as toxicologist I find this to be really interesting in ways we can try to help manage this for patients because again addiction can be very very uh debilitating can be very very dangerous for people um two main different types of receptors we're going to see here D1 and D2 D1 tends to be stimulatory mean it usually stimulates enzymes like AAL cyclas for example which forms cyclic a ATP um we'll also find uh that D2 is going to be inhibitory so this is going to be inhibiting the actions of that enzyme there okay so just know those two uh and how they're going generally function what dopamine generally does I mentioned serotonin being the kind of feel-good neurotransmitter here um you will frequently serotonin being abbreviated as 5ht that's because the chemical name for this is five hydroxy tryptamine and so that's just a common shorthand way of writing serotonin so if I say 5ht receptors you'll know that just means a serotonin receptor here and so these are going to be metabolize or uh made through tryptophan to a degree um we're going to see that in terms of synthesis and then metabolism is going to be through that monoamine oxidase so here um it is chemically different enough from your mono or your catacol meines like nor my friend for example that that compt doesn't really have anything to do here but because serotonin is still what we consider to be a monoamine based off his chemical structure Mao still works on that so like I mentioned we used to give patients who were depressed monoamine oxidase Inhibitors that boosted up levels of serotone because now it's not being metabolized as much and then patients mood started to change started to feel better they're less depressed less likely to commit suicide um again not the full story we'll talk more about that as we get into like Behavioral Health topics and whatnot but its role is to help with things like mood uh helps with things like anxiety part of that sort of uh uh that sort of anxiety SLS survival sort of pathway can be mediated through here so oftentimes you're going to find patients who have um issues with say depression they often have problems with anxiety too so the two tend to go hand in hand with one another um part of that it can be mediated through helping to correct serotonin levels um but it does lots of other stuff too so for example um we have certain serotonin recept certain serotonin receptors um that cause nause and vomiting that can either be in the brain itself or coming from say the GI tract so one really popular drug I'm sure most of you have heard of uh is called Zofran or onanon is the generic name that's actually a serotonin antagonist at certain types of Serotonin receptors and that helps to alleviate nausea vomiting so if someone was having um too many drinks and they got really nauseous or they're receiving chemotherapy they could receive a serotonin blocker like zofran and that makes them feel million times better cuz I don't know if anyone likes to be nauseous but it is a miserable feeling and can work really well by blocking that serotonin to help alleviate that um can also affect cerebral blood flow so for example it can help to um control whether or not you get a migraine can be through serotonin's effects on cerebral blood vessels so a lot of different subtypes of receptors I'm not going to get into all the details here certainly in the pharmacology courses we're going to talk a lot about those when it comes to different types of Serotonin receptors there's like 14 of them that are known so far but could be others down the line that we that we recognize that we don't know now but anyway lots of different receptor types uh so someone has a question here could can you explain why you would use a dopamine drip it's a great question youever here like watching like a medical show and they're like give me dopamine 20 stat sounds sounds exciting um so it's interesting about that is is if we go back to let's go back to our slide here so if if you look at the formation of norepinephrine you can see here that tyrosine gets converted into levadopa which turns into dopamine which eventually turns into norepinephrine so that happens out in there up in the brain certainly which can help with the normal function orine nephrine but also happens peripherally in the blood and so one thing that we can do is by giving a dop and normally dopamine can't get across the blood brain barrier so I could give a patient with Parkinson's where they having a CNS defici of dopamine I could give them a dopamine drip and it does nothing for their Parkinson's because dopamine can't get across that blood brain barrier if I give them the precursor this leave aopa that does get across to get converted to dopamine so if we see the drug called cinat is a drug that's consisting of levadopa and another drug won't get into the Weeds on um to be able to help correct their deficiency of dopamine when you see a dopamine drip you're typically thinking about like the ICU or the ER type of setting here and what's nice there is that peripherally you're going to find that dopamine gets converted into norepinephrine now why might that be useful well because now you have a bunch of extra norpine phrine that can activate all these adrenergic receptors so if I were to have a patient who comes in who has really low blood pressure they're hypotensive maybe due to infection maybe due to blood loss could be million different reasons what I can do is start up what I call a dopamine drip with just a continuous infusion of small amounts of dopamine to be able to then activate these Alpha receptors and beta receptors and what that will do is cause basically kind of like an artificial fight ORF flight response where you're going to see that their blood pressure will come up heart rate will be stimulated as well similarly I could just do a Norine drip that's available too and that way you're kind of cutting out the midlan so to speak um but that dopamine has been traditionally Ed that way for helping to control patients blood pressure and heart rate and whatnot uh for a very long time so that's where you get the dopamine drip from okay again I want to get too much in the drugs I see sometimes see that on reviews they're you talk too much about the drugs this is not a farm course but it's so like they're so integral in my brain it's hard to separate them out anyway so next up we have Gaba another fun neurotransmitter here gamma amuno butc acid which it's abbreviated to Gaba um and so this is actually made from another neurotransmitter we're going to see here in a second called glutamate and actually what you're going to find here is that glutamine which is a precursor to glutamate um gets converted over and then this will get converted over into Gaba um this actually requires a vitamin for this to occur which I'll talk more about that in a second here but vitamin B6 is or p doxine is necessary for this conversion to convert glutamate over into Gaba how we metabolize it there's an enzyme called Gaba transaminase that will break it down which eventually will get glutamine glutamate back out of that um so why these are important is because Gaba is what we considered to be the major inhibitory neurotransmitter meaning that when it gets released from the synapse or into the synapse here what this is going to do is activate certain receptors which help to hyperpolarize the postoptic on so in particular we have two main Gaba receptors Gaba a and Gaba B Gaba a is the more important one for scen this functions we're going to see but these open up chloride channels so that means when you're releasing this you're going to be open up these Gaba channels here chloride flows in and it's much harder for this neuron to have an action potential why might that be useful well if for instance you have twoo little Gaba activity the neurons are going to be too excitable cuz you're taking your foot off The Brak so to speak meaning it's going too fast you can be more likely to see a seizure because you're having this abnormal neuronal firing so what do we do to help treat patients who are having seizures well we give them medications which help to facilitate Gaba binding here to help to make sure we open up those channels to allow the chloride to flow in to hyperpolarize those neurons to stop the abnormal firing of action potentials and stop the seizure similarly if you are anxious you're getting a lot of too much signal activation in the brain causes you to be anxious and not go to sleep so we can give similar drugs so there's a set of drugs called the benzo aines we can give and these are literal chill pills like a Xanax for example you can give that it will help to facilitate Gaba binding here to have more CLA flow in so instead your brain going a million miles a minute Cal down chill out that's the way the drug will work basically and so through facilitating Gaba action here so Gaba major inhibitory or transmitter the break on the car that is your brain so to speak so the flip side kind of like the the the yin to the Yang of Gaba is glutamate we mentioned that glutamate is a precursor to Gaba but glutamate itself is a neurotransmitter and what's interesting is how glut Gaba is the major inhibitory neurotransmitter glutamate is the major excitatory neurotransmitter so glutamate being excitatory does get eventually converted into Gaba which is inhibitory so they have miror opposite sort of actions there right and so glutamate here we mentioned is made from glutamine and you can see gets metabolized into Gaba through that glutamic acid DEC carboxilate so glutamate is necessary to eventually get the Gaba that helps to hyperize neurons but mainly we see glutamate activity here it's going to be excitatory I mean it's going to be activating or um sort of stimulating The postoptic receptors to cause some change to happen here um what's interesting though is that you can actually have too much stimulation that can actually cause something called ayto toxicity and part of the reason why we think some people develop things like Alzheimer's disease for example is because of too much glutamate activity causing too much receptor stimulation causing eventually cytotoxicity of the cell leading to cell death if you over stimulate a cell as part of a protective mechanism it will undergo apotosis or basically cell suicide and so that's the reason why I think some people get dementia on Alzheimer's is through too much glutamate activity and so I mentioned before that it is necessary to have B6 around to convert glutamate into Gaba and one thing you can actually run into if you have a severe deficiency of vitamin B6 that conversion doesn't happen and so what would happen well if I can't make Gaba that necessarily means I'm going to have a buildup a glutamate so how that would manifest seizures right because you're getting way too much oyot toxicity happening so it's important to maintain balance all these things even something as innocuous as a B vitamin like B6 can be integral and be hugely necessary for normal Nal function even happen here what receptors is glut going to bind to there are several that are out there um so for example the nmda receptor um lot things like The ampa receptors there's other metabotropic ones this one's a little more nebulous there's still active research going on to try to kind of sus out all the different glutamate receptors here um the nmda receptor is one of my favorite ones because by blocking that receptor you get some really interesting effects that can happen in patients and so one drug that does this is a drug called ketamine uh where basically ketamine me is an nmda receptor antagonist meaning it blocks glutamate and so what this will do if you have a patient who needs like a procedure done like for instance um they have a broken bone that needs to be set or they have a joint out of place that needs to be set um we can give the drug camine and what this will do is cause what we call a dissociative anesthesia meaning it kind of like causes almost like a mind out a body experience for the patient to where whatever signals like kind of somatosensory signals are coming from the body they never make it up to the brain so the patient doesn't feel the pain when you're trying to set that bone doesn't feel it when you're putting that joint back in place uh and they're having a great time I don't know if you noce but Kine can also be used as a means of a substance of abuse people can get high off of this uh if taken in the correct amounts so really really interesting stuff that can happen either by blocking these receptors or activating them that's where we're get into the pharmacology stuff later on anyway there are others that are out there so for example glycine U is important for inhibitory actions on the spinal tract right spinal cord um interestingly there's a poison called strick Nine which you don't really run into often times in nowadays but this actually inhibits glycine there and if you have too little inhibition in the spinal cord you actually end up seeing severe excitation you can see severe muscle contractions it's is very very very painful for the patient eventually can lead to death um histamines a really important one so this gets secreted from the hypothalamus and can do a host of different things here including uh affecting your vasculature meaning like how constricted or uh dilated the blood vessels are can affect body temperature levels of arousal a lot of this is through the H1 receptors I'm sure in our GI lecture they talked about H2 receptors and how that's useful for producing stomach acid up in the brain those mostly histamine one receptors here um so for example if you've ever taken the drug called badril badril is an anti-histamine meaning it blocks histamine at the H1 receptor and I don't ever taken to badol before but one of the common side effects is caus you to be sleepy because now you've blocking the histamine here can't do its job to raise that level of arousal um some people do that on purpose because they want to go to sleep for example so you ever seen the drug Unisom it's another antihistamine that can be used to help facilitate sleep depends on what the problem is going on nitric oxide this is going to be helpful for controlling certain aspects of behavior long-term memory um we even have our canabo here like the CB1 receptors um that can affect things like your appetite can help to be um you affect nausea vomiting so these canabo we think about traditionally being affected by products of marijuana so we think about things like THC that I mentioned before um CBD or canabidol is another one here that can affect these receptors um so it can affect you know do a patient have that sensation of being high uh can affect memory appetite you you get the munchies when you smoke pot right um so lots of different things that can be uh affected through these different receptors here through these neurotransmitters keep in mind this list is not all inclusive not going to cover every one I just want to hit on the main High Target ones that you're going to be seeing affected most frequently okay so real briefly just to go back through and talk about our Action potentials here um we're going to see that normally your neurons are going to be at a resting state so we think about like the resting membrane potential being like 70 molts right um meaning it's more negative on the inside of the cell more positive on the outside and so that's important because at rest we don't want to have abnormal firings here but when a signal comes along it can cause a depolarization right so you see that rapid Spike and electric potential there and then it's going to come back down so then it has to repolarize in order for the next signal to come along to reactivate it here remember hyperpolarization just means when the cell potential goes below the resting membrane potential and that's going to be important for helping us to determine where our refractory periods are if you recall uh with those in just a second we'll talk about that again so again during this initial uptick in electric potential this is the depolarization then we're going to have the resetting of the neuron we're going to have a repolarization where you get this hyperpolarization and then it goes back to resting membrane potential and if you recall the reason why we could maintain that resting membrane potential is because of the sodium pottassium atpa pump so when you see this hyperpolarization here that sodium pottassium pump's going to be kicking in to be pumping sodium out bringing potassium in and that will help to basically get you back to that resting state and again depending on different factors that rest and membrane potential may be higher or lower and that can affect how sensitive that neuron is to having the next action potential the higher that resting membrane potential is the higher that set point the more likely it is to Fire and so that could be bad in some cases maybe good in others if you recall we're going to see that with this initial depolarization so you get the stimulus coming in here we're going to see the sodium channels open up right so sodium floods into the cell because it's going along the concentration gradient the sodium will go into the or the sodium channels go into that inactivated state right where they're going to start to the reset process here and then for the repolarization potassium channel is opening up so potassium is Flowing out that causes the potential to come back down because remember potassium is really high concentration within your cells that will then allow for the repolarization to happen here you get the hyperpolarization and then we get back to our resting state through the actions of the sodium potassium atpa pump okay now the sodium channels have had a chance to reset themselves and the process can happen all over again and again the higher this resting memory potential is the closer you to this sort of gated threshold the more likely are to have maybe an inappropriate firing versus if I were to hyperpolarize the neuron say for instance I were to flood the brain with Gaba this would allow for a more negative potential to be the setting set point thus making it more difficult to have that neuron fire so like I said if you're having a seizure we can give a drug that helps to facilitate Gaba working to help lower this potential here to make it more difficult to have an abnormal firing thus patient can arrest that seizure or you put him to sleep or what you need to do if you recall a refractory period super necessary to maintain normal function to make sure we're not going to have inappropriate or abnormal firings of these neurons here so um the absolute refractory period if you recall is the initial stage here this is where those sodium channels have gone into the inactivated State and does not matter how strong a signal comes in no additional AC potential can happen here right however once we're getting to that point where we're opening up those potassium channels now we get into what called the relative refractory period meaning some of those sodium channels have gone back to the resting state and if you have a strong enough signal coming in then that can cause an early depolarization leading to an abnormal signal potentially and so um interestingly I had a had a student one time who had a sister with very severe epilepsy I mean just on tons of different medications nothing tended to work and what it turns out was there's just one part of her braid that was sending these abnormal signals that were getting her to have a seizure when it was activating these neurons when they were in that relative refractory period State um so ultimately how did they fix it well they actually surgically went in removed that tiny portion of the brain all of a sudden no more seizures she was completely cured not on any anti-epileptic medication it's incredible most seizure patients don't have that option or their diseases pathophysiology such that won't work um but it's really interesting how in some case there just a tiny little bit of tissue that's sending those signals there and it's activating all the neurons when they're at that sort of that relative refractory period causing just complete chaos to happen and thereby causing a seizure to happen right and again depending on all the different inputs onto the neuron will make it more or less likely to want to fire off an action potential here um so we can see this excitation by one neuron causes an increase in membrane potential cross a Soma so you notice here you get this excitation here causing the rting membrane to increase and eventually if you get to that threshold boom an act potential gets fired or I could have inhibitory signals coming in which will hyperpolarize that so if you imagine Gaba being released from this neuron onto the Soma here you're going to cause it become more negative thereby leading to less chance of for this to fire off right um so you're going to have millions of little inputs onto the neuron and ultimately what the overall math adds up to be all your pluses and all your negatives you're going to get some final answer that says either we're going to get this inhibitory signal or overall it's going to be excitatory and so we can either see this happens in a process that is what call spatial where you can have multiple inputs from different neurons that all will kind of sum up into having an ex potential or having an inhibition or it could be temporal where we're going to be having the same neuron firing multiple signals enough to which you eventually get to the set point here where this is okay boom we're going to have an acttion potential okay um what we're also going to find is is that depending on where the synapses are happening we're going to find that when they're closer to the axon where there's a lot of those sodium channels they're going to be more sensitive there to those changes either excitatory or inhibitory um whereas if you're out way further along the dendrites here these are going to have much less of an input just because the signal sort of gets lost a little bit as you kind of travel through the Soma to the axelon where the actual a potential is going to be generated so as a result of that signals that happen here are going to be much more influential we should say than signals are going to be coming in from here right even though you have a bunch of excitatory signals coming in on the dendrites it's never going to be enough to actually cause because you have this stronger inhibitory signal at the axon so good ability to stifle the ation potential right and the neurons can wear out right you can see fatigue that happens after being constantly activated there um it's important for natural termination of seizures uh as we sort of mentioned there but it's also a protective mechanism because too much too many signals being sent in too many action potentials can lead to that what call that ayto toxicity which can lead to cell death which we don't want that to happen there um so part of this is either we losing presynaptic vesicle content so you're just kind of flooding uh out all those neurotransmitters and you just run out and it takes time for the body to start to reproduce those um you can see in some cases we're changing the poptic receptors where maybe we're having like down regulation there's fewer receptors to be activated there or we may find that depending on the ion concentration than the postseptic self that changes enough it may make it where it's really difficult to have an actra potential as part of that kind of fatiguing sort of mechanism there even things like pH can affect this so for example alkalosis increases neuronal excitability which could potentially cause a seizure versus acidosis decreases excitability so for instance if we have someone who's hyperventilating I if you ever seen like a TV show or cartoon where they start to breathe into a paper bag why is that well they're in the middle of like a panic attack for example they are possibly breathing quite rapidly because they're having that fight ORF flight response well you're losing CO2 losing that CO2 what does that do to the blood pH well it's going to cause it become more alkalotic was that do to the CSF pH it's going to become more alkalotic meaning you're going to be just further exacerbating that hyperexcitability someone breathes into a paper bag for example they're not breathing in new fresh air they're going to be recycling that CO2 that they're breathing off so they're actually inhaling more CO2 that brings the pH back down and hopefully it can help to calm them down a little bit probably not the best recommendation to treat a panic attack but that's you know commonly how why why they would do that we can find that hypoxia uh is hugely influential on the brain here um lot of necess or a lot of Need for oxygen in the brain for normal function here and even loss of see this blood flow for a couple of seconds is enough to cause unconsciousness so very very sensitive to changes in blood flow um we're also going to be seeing things like you know changes in blood sugar can be hugely effective here because the brain doesn't have a lot of stores of glycogen for energy uses it needs glucose and so if you're not providing that because the patient's hypoglycemic that's going to be a problem actually one of the things you can see if the glucose is too low is unconsciousness and seizures uh because the brain is not getting the energy that it needs um certainly we can find drug effects here are hugely important um most of you have probably consumed some amount of caffeine today if I were to guess caffeine and its cousins theob bromine so you find the bromine at chocolate for example uh and then the drug theophine they can increase neuronal excitability because they block a neurotransmitter called a dennine and so by drinking a big cup of coffee or a Red Bull whatever the case may be you can actually increase neural excitability and that can increase levels of arousal and awakeness right so you can study for your exam coming up as a case may be can that be taken to an extreme absolutely Ely where you can find cases where patients can die from having too much caffeine because of this Iden antagonism leading possibly to seizures right we'll find sedatives and anesthetics those are useful for helping to make depolarization more difficult that's great if we need to put the patient to sleep for surgery for example if we need to have um treat their anxiety or treat their seizures so again drug effects are going to be huge here in their brain we'll talk much much more about this uh probably adium uh when we get to the pharmacology courses all right um second thing want to talk about here today is going to be sensory function um we'll talk about vision and hearing and um old faction in another section here we're just really going to talk about the basics of sensory inputs here hopefully I'll finish on time otherwise I'll save this for the next time we meet here um some a question they said would glutamate increase making more positive the resting memory potential generally yes um cuz you you'll find that a lot of The receptors that um glut will effect can include things like calcium channels so by activating certain glutamate channels it actually causes calcium to flow in and that increases the electric potential meaning it's more likely to fire off an action potential um that's partially why we see that excited toxicity that can happen and part of the hypothesis where people develop neurodegenerative diseases like Alzheimer's is because they've had too much oyot toxicity in those cells and it's killed them off and that can affect your memory it can affect your cognition all kinds of things as well so certainly yes I would say that definitely increases for most of the receptors there not I wouldn't say all of them necessarily but U generally speaking glutamate would make the potential higher more positive thus meaning more likely to have an action potential as I'll tell you there's um there's a certain drug that we used to treat tuberculosis it's called isid and one of the recommendations they always give is you need to take it with vitamin B6 and part of the problem with Ison is that if you don't it can actually cause a depletion of B6 in the brain and thereby it causes um you can't convert glutamate over into Gaba and so one of the problems you can run into if you have someone who's taking iiz and maybe too much of it uh no B6 it can actually lead to seizures happening because of that balance of you're kind of tipping the balance towards glutamate meaning more hyper uh excitability meaning more likely to have a seizure occur there so just another little example all right so when we think about uh Sensations right we think about being able to detect things like touch and pressure and and heat and pain and all of that um several different receptors are going to be necessary here so first of which are going to be chemo receptors they're going to be detecting changes in chemicals in the environment so taste smell for example here um those are chemo receptors photo receptors are sensing light as you might imagine Thermo receptors for temperature and The mechano receptors are going to be really necessary um for things like hearing when you have like sound waves coming into the uh infecting the tanic membrane for example and then also for things like mechanical um they touch and uh texture vibrations those are going to be through mechano receptors uh pain receptors another one we'll talk about as well how that signal transmission happens um sometimes you'll see pain receptors also called noors so notion is the sensation of pain uh and it's going to be through those pain receptors as we're going to see so you kind of go back through and we we'll talk about the specifics of these as we get into them uh get to the appropriate section here so I mentioned noors this may be trigger triggered by things like heat or cold high pressure could do this even chemical irritation um I never forget one time I was in organic chemistry lab and accidentally um had some kind of strong Bas I get on my skin uh and severe burn you know um not severe burn I should say but the burning sensation was very severe even though the temperature was not hot it gave me that burning sensation from those chemo receptors being activated there um we'll also find that perception of pain cuz how we perceive pain is going to be really dependent on on things controlled by the CNS so it's not just the external stimuli but also things like what's our emotions like um what's our expectation of pain and that can certainly can affect things um so for example if you think something is going to be painful it may feel more painful for you than if you were like it's not a big deal so for example A lot of people are needle phobic because they're worried about the needle stick being really painful perhaps some people got no problem with that so they may not perceive as much pain just a little light prick real big deal so again they can really color things for sure um mind over matter is a big topic we'll talk about as we kind of go through and discuss some of these different topics here anyway um other sensory inputs can include proception which is going to be sensing movement um so these are going to be a number of signals coming in from the muscles the tendons and the joints these are necessary because it helps the body to be able to detect what position it's in um and then along with other inputs like you know hearing um or your uh vestibular apparatus in Your Vision um can help us with things like equilibrium so that way if I go and I were to give you a gentle shove in the shoulder um you're not just going to fall over like a sack of hammers like you have the ability through certain reflex arcs and based off this SL uh slat sensory input your brain can say wait a second let me activate something so that way I don't fall over right a lot of that superpro exception um cutaneous receptors these are going to be responding to things like touch and pressure heat pain all that and then our special Senses we'll get into greater detail uh in the probably the third PowerPoint second the third power points there um and so if you notice here like proception notice like 10% of it's coming from their visual input 10 or 20% is coming from your vestibular apparatus and then 70% is coming from the muscles here so that way you kind of know you feel where your body's at you can feel what position the body's in to make sure you're not going to just like fall over the lightest gust of wind for example here it's all really important so when we are looking at say nerve endings and actually getting this kind of apprpriate reception uh to a cur we're going to see there's many different ways this can happen so um for example we could have actual mechanical deformation of the neuron itself so for instance if I were to say push on this neuron here that actually can open up sodium channels to then cause an action potential to be developed to then send a signal to the brain saying hey my finger is being pushed down by something right Um this can occur through chemical interactions with the membrane changes in temperature even electromagnetic radiation can affect these nerve endings to say hey we're going to send a signal that says this is what input we're getting here um as those ion channels open again that develops an action potential because you're going to have sodium flooding into the cell causing that threshold to be met to generate the action potential there and then depending on the degree of frequency or the kind of repetition of action potentials that will determine the degree of sensation right so if I'm getting just a single action potential it may not really sense very much but if I start to get many many many signals coming in here I'm going to be sending a lot more information to the brain it's going to give that priority to be like hey I'm feeling that sensation now and remember the brain gets a ton of information every single second 99% of it's useless the brain LS is new and novel inputs so changes in inputs especially that it's going to give priority to and we'll see that there is a bit of fatigue that comes with that but we'll we'll see how that works so in some cases here we have what we call phasic uh responses so certain nerves are going to be more so um dealing with these phasic responses where the ini stimuli will cause a lot of action potentials but then eventually kind of wears out your body kind of adapts to it and you're going to be sending fewer signals to the brain and thus it's kind of like your body just kind of getting used to it and you're not really noticing it anymore um so for example you probably don't feel the clothes on your skin right now because you got that initial stimulation as you put on your clothes but then over time your body's like okay well I don't really care about that info anymore it's not useful here so let me know when something changes and then it'll go back to this kind of Rapid sensory input but that's why these are phas it because you get this initial increase in action potentials it'll be very vigorous and then it will start to die out as that signal is or as that sensation continuously felt there so smell can happen like this you kind of get used to certain smells touch temperature there's a certain drug that we use um to treat uh cenan overdose Tylenol overdoses uh it's called in acetal cysteine we also use it sometimes uh for respiratory therapy because it helps to break up mucus in the lungs the problem with it is has a lot of sulfur in it and smells like rotten eggs and so part of my job my first time as an intern in a hospital pharmacy they had big you know 30 ml bottles of in AAL cisem but the respiratory teexs only needed like 3 MLS so they needed someone to take the inal cistin from the big bottle and put into the little bottles and guess whose job that was to deal with the stinky in aetl cistin the new guy so I spent basically spent the summer smelling this stuff all the time to the point where it doesn't smell like rotten eggs anymore to me it smells like just like regular eggs which concerns me cuz now I don't know can I detect a rotten egg anymore I don't run into them that commonly to know the point being is that say phasic response you're going to see here temperature does this touch does this smell does this for sure on the other hand we're going to find that tonic receptors are going to be able to continually send those signals to where the adaptation is very slow and so as long as that stimulus is applied it should be sending those continuous action potentials here so for example things like pain your body wants to know when it's in pain so that can remove that stimulus to go back to your Baseline so if your hands on a stove you do not want to get adapted to that pain because you're going to be causing bodily injury so you want to make sure you're continually sending those signals there until the stimulus is withdrawn um similarly for things like the vestibular apparatus like your brain needs to know kind of at all times where you're at in time and space to make sure you're not going to get dizzy and fall over Barrow chemo receptors in the cardiovascular system I want those to be working all the time because if my blood pH starts to plummet or my uh CO2 levels start de climb I want to be able to respond to that and so it's necessary for those kind of tonic responses there and you can see this adaptation or accommodation that happens it can be related to the specific tissue type so for example your joints and your muscles you kind of want to know what position your body's in at all times to maintain stability so these are pretty slowly accommodating meaning it takes more time for these to accommodate than something like a hair receptor or the pacinian Cor pusle you'll find in the skin these adapt really really quickly which again you don't feel the clothes you're wearing most of the time because that's a phasic response the body gets used to that very quickly so it's like okay no changes here I don't care about this signal versus if my standing up for eight hours a day as a cashier public for example the joints and the muscles need to be sending those signals constantly to be like hey okay shift the weight this way shift the weight this way based off of all those inputs from STI apparatus and your eyeballs that kind of stuff right all right so let's talk about the skin I'm not sure if I'm I'm going to be able to finish this whole thing but we'll we'll see there a lot to get into a lot of details and things like that a lot of examples um so I might try not to go over so I'll probably end it at 4:30 here trying to think um I can cover the whole thing or not going talk about pain response yeah okay I'll just talk about the skin real quick and then we'll we'll wrap up and we'll talk about the actual transmission of sensory Pathways here U okay so Skin So couple different types of cutaneous receptors that we're going to find here um so first of which going to be free nerve ending which you can notice on the picture here kind of where they're located at um this is good for like light touch or changes in pressure um pain is going to be transmitted through these free nerve endings here and then temperature uh sensation is going to be there U merkel's discs are going to be better for touch like when it's indented so like kind of deeper pressures um or higher pressures that may be able to detect there meiser's cor pusles is another good term to say um you'll find this is response to things like vibration and touch and then we'll have those bining cor pusles which are going to be good for detecting sort of like rapid changes in the mechanical state of the tissue and then also vibration to a degree and then these rafini endings which are good for skin stretches most of these are going to be working in tandem with one another to be able to provide that very kind of like pinpoint accurate information to say specifically what's happening in the tissues themselves of the skin another picture just kind of showing the different um nerve types and kind of where they're sort of situated U to be able to send in all these different sensory signals um and again we'll find that the density of receptors um can vary depending on the tissue that you're dealing with too so for example places like the fingers are going to be much much more sensitive um to changes in things like pressure uh pain things like that than say for instance like the middle of your back just because your hands needed are needed to do these kind of fine things and so it needs a lot of fine information to be able to detect okay well you know if I'm trying to do surgery for example you want have a very steady hand we don't have a lot of dexterity you need a lot of sensory input to be able to help control that okay so I'm going to go over the sensory Pathways I think I'm going to save this for the next time um just to make sure we kind of all talk about it together um so we'll finish this up the next time we meet which I'm not sure when that is uh and then we'll also then get into Vision which I think I should probably be able to get both of those down at the same time let me see here so we will meet good okay so we have like a two 4our block on Tuesday so that would be a good time to kind of finish up this section and we'll continue on with this stuff so uh any questions I can answer at this time if not you're free to go I'll hang on here for another minute or two thank you Yanni for Indo please wasn't Indo today I don't you have any any good Endo questions probably like two or three of them I'll do one for the neuro stuff um with the Endo stuff I thought you had the test today it's tomorrow oh really they push your exam oh well there you go yeah the Endo stuff should be pretty straightforward um so for the Endo stuff um oh they moved it okay I got you wonder why um so for the Endo stuff again keep in mind like just the pathways um in terms of like which sort of like hypothalamic hormone is going to activate which other hormone in the pituitary and then what does that then cause release of into the body you want to know kind of like the general effects of different hormones so for example like how does thyroid hormone what are its functions as compared to I say for instance like parathyroid hormone right so General functions there also know which ones are antagonistic to one another so for example you need to know something like insulin and glucagon will block each other essentially because they're going to be having opposite physiologic reactions or G growth hormone and somatostatin for example um are going to be antagonistic to one another other than that it's not like getting super in depth and like talking about things like diabetes for example because it's not really where we're at um so it should be should be good to go but good luck on your exam um I definitely get a cahoot for the neuro stuff just because I feel like it's much much more difficult terms of topics but all right I guess get an extra day of studying that's that can't be bad right all right I don't see any other questions so you guys have a good one I will see you next week bye