the human brain is capable of storing information for as little as 30 seconds in short-term memory for a lifetime in long-term memory think about the last time you studied for a test the process of studying activates various pathways within your brain the continued activation of these pathways is what leads to memory retention for long periods of time long term memory has been associated with a horseshoe-shaped structure within the brain referred to as the hippocampus this structure is found in both hemispheres of the brain within the medial temporal lobe and coordinates the storage and retrieval of memories a closer look at the hippocampus reveals some major structures the dentate gyrus the ca1 and CA 3 regions memory processing begins when signals enter the dentate gyrus from the internal cortex via axons of the perforin pathway granule neurons a type of cell within the dentate gyrus synapse onto pyramidal neurons within the ca3 region the ca3 neurons connect their axons referred to as Schaffer collaterals to the ca1 pyramidal cells from here the information is passed to the cibecue ylim and then back out to the internal cortex a process referred to as long-term potentiation LTP is thought to be the cellular and molecular underpinnings of memory LTP is a long-lasting enhancement in signal transmission between two neurons after repeated stimulation LTP has been most commonly studied at the synapse between the Schaffer collateral axons of the ca3 neurons and the ca1 pyramidal cells a closer look at the ca3 ca1 synapse reveals various structures that are involved in LTP on the post synaptic cell are both NMDA and AMPA receptors these receptors are usually localized together at many postsynaptic sites and are activated after the binding of the neurotransmitter glutamate the AMPA receptor is permeable to sodium ions the NMDA receptor is also permeable to sodium but more importantly it has a high permeability for calcium the NMDA receptor is also blocked by magnesium which prevents the ions from passing through the receptor when an action potential travels down the Schaffer collaterals it leads to the release of glutamate which binds to both the NMDA and AMPA receptors when a low-frequency action potential is propagated down the Schaffer collaterals a small amount of glutamate is released the AMPA receptors will open and allow an influx of sodium into the ca1 post synaptic cell this causes a slight depolarization event in the postsynaptic cell the glutamate also binds to the NMDA receptors but no ions will pass through the pore due to the magnesium blockade while the small amount of neurotransmitter release signals a response it is not enough to cause LTP this is comparable to you studying material for only a few times you will not activate a high-frequency action potential from studying for just a short while when a high-frequency action potential travels down the Schaffer collaterals to the terminal a larger amount of glutamate is released from the presynaptic terminals this is comparable to you studying for longer periods this results in higher frequency action potentials when glutamate binds to the AMPA receptor a greater depolarization event occurs the AMPA receptors remain open longer due to the increased concentration of glutamate which allows a larger amount of sodium to enter through the AMPA receptors this influx of sodium causes a large depolarization event in the postsynaptic cells which repels the magnesium blockade from the NMDA receptors through a process known as electrostatic repulsion at this point the NMDA receptor with glutamate bound allows sodium and calcium to enter through its pore in this way NMDA receptors are known as coincidence detectors because they require a presynaptic and postsynaptic event for channel opening the binding of presynaptic Lee released glutamate and a significant postsynaptic depolarization via activation of the AMPA receptors as previously mentioned LTP is the process of strengthening the connections between two neurons the influx of postsynaptic calcium acts as an important secondary messenger activating many secondary intracellular cascades the increase in calcium contributes to two phases of LTP early phase and late phase during the early phase the calcium binds to its respective binding proteins and causes the insertion of new AMPA receptors onto the postsynaptic cell membrane at the active CA 3 CA one synapse these AMPA receptors are stored in the post synaptic CA one internal cell stores and will only insert when there is a large influx of calcium through the NMDA receptor this allows more AMPA receptors to be available for future depolarization events the early phase changes lasts for only a few hours and require a brief increase in calcium levels during the late phase a prolonged influx of calcium causes an increase in transcription factors ultimately resulting in gene expression and new proteins to be synthesized some proteins resulting from this process include ampere receptors which are inserted into the post synaptic cell membrane at the synapse in addition there is an increase in the synthesis of proteins called growth factors these are involved in the formation of new synapses which is the basis for synaptic plasticity your brain can change as you learn these synapses are formed between the ca3 ca1 neurons allowing for a straw longer connection between the two neurons the late phase changes can last 24 hours up to a lifetime it is important to remember that LTP is not a mechanism it is an outcome of the increased activity between two neurons this results in an increase in AMPA receptors and synaptic connections which allows the low frequency action potential to cause a greater depolarization event in the post synaptic terminals this is the foundation of memory however the hippocampus is not the only brain region that processes memories memory processing occurs in many other regions including parts of the cerebral cortex studying activates various pathways throughout your entire brain continuous activation of the same pathways will create high frequency presynaptic action potentials and post synaptic activation in those paths it is now clear that these pre and post synaptic events strengthen the connections in a specific pathway this strengthening is what contributes to your ability to recall the material when writing your exam you