FSU EXP 3422C - Conditioning and Learning Test 1, Part 2

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Conditioning and Learning Test 1 Part 2 6 2 15 Lecture on LTP Introduction So How Do We Do This o The whole point of LTP Long Term Potentiation Preparation is to simplify things in order to get a clear look at the synaptic mechanisms of learning and memory it is conducted in a slice of hippocampus removed from a rat s brain This process shows Hebb s Rule states that the synaptic strength between 2 neurons should increase if the 2 neurons are active at the same time this plays a role in terms of classical conditioning when something you want to learn is paired w something you already know firing the two neurons simultaneously Instead of pairing two things LTP uses sustained high frequency stimulation Tetanus to fulfill this role o We need a slice of hippocampus kept alive in a dish w artificial cerebro spinal fluid CSF stimulating electrodes next to Neuron A and a recording electrode next to Neuron B A makes one or more synapses onto one or more dendritic spines of B We stimulate A with the electrode until B starts to fire in response to A while we record the action o Background Hebb published his work on synaptic strengthening in 1949 Essentially you excite a neuron with an existing connection and then add on a neuron that would not usually lead to that response After this synaptic strength then increases between the 2 other neurons learning approximated by LTP Hebb s Rule UR happens with US but bring in the CS enough and the response starts to follow the unknown o LTP is very artificial but it is a good simple model for actual learning in the brain helps us to understand things more easily Inducing and Measuring LTP involves a 3 Step Process o Step 1 Test Baseline identify a level of presynaptic glutamate release that produces a weak post synaptic response EPSP a small response from Neuron B this step gives a stable reading of the connection between the 2 neurons o Step 2 Tetanus produce a level of pre synaptic stimulation that drives the post synaptic cell to full depolarization to generate an AP You maintain the stimulation long enough so that the pre synaptic cell releases glutamate onto a post synaptic cell already generating AP s fulfilling Hebb s Rule o Step 3 Retest stimulate just as in step 1 but a greater post synaptic response larger EPSP should be observed after stimulating together the synapse between the neurons should be stronger Understanding LTP Methodology o Test stimulus serves 2 functions establishes a baseline and is used to determine if the inducing stimulus produced LTP connection was stronger AND it lasted for longer than normal o The induced stimulus tetanus in this case is analogous to the learning event and the stabilized stronger potential response is analogous to memory o The tetanus allows for coincident activity meant to strengthen the relationship b t A and B with this the same amount of stimulation in A NOT necessarily full depolarization produces a bigger response in B o Ca plays a huge role both in initiating and maintaining LTP learning and memory it works through 3 processes discussed later Memory is further broken down into transcription and translation 1 and 2 as Here s a Breakdown of the Process at a Neuronal Level step by step in order they apply to neuronal connections the third is learning o When tetanus is applied glutamate goes across the synapse from Neuron A to bind to AMPA NMDA and mGLUR1 receptors the AMPA receptor opens ionotropic and lets in sodium to allow for initial electric stimulation o Once Neuron B gets depolarized and w glutamate already present NMDA receptors which are double gated 2 requirements also ionotropic open and allow in calcium o That calcium journeys to B s endoplasmic reticulum ER receptors for calcium which releases calcium back into the vicinity of B s dendritic spine o mGLUR1 gets activated and released IP3 2nd messenger to the ER where it releases calcium into B s dendrite At the same time the voltage gated Ca channels open and allow calcium into the cell body o After tetanus the spine receiving stimulation B is now bigger due to the calcium in the dendrite Ca in the dendrite is for translation and protein synthesis this keeps the spine wide large o Ca in the cell body activates a kinase phosphorylating the transcription factor CREB which then drives transcription of new mRNA these go all over the cell The copies that end up near the spine where learning occurred are translated by the calcium in the dendrite translated locally ONLY in that area Calcium in the spine enlarges it through learning maintaining the size of the spine anatomic memory and allows room for more AMPA receptors and a bigger EPSP on Neuron B during the retest more sodium flows through o After everything there should be an altered AMPA NMDA receptor ratio more AMPA o For extra help look at slides for LTP on blackboard visuals tend to help with o LTP is the result of changes in post synaptic spines use of AMPA receptors ionotropic open and allow Na inside responsible for post synaptic depolarization and NMDA receptors ionotropic allow Ca inside but are double gated and need the post synaptic potential along with glutamate and mGLUR1 receptors metabotropic receptors releasing 2nd messenger IP3 than NMDA understanding this Overview EPSP moves the Mg block in NMDA receptor NMDA is necessary to know that both neurons are firing it only opens in this case o The weak test stimuli can only open the AMPA Kainate receptors this is the MAJOR difference Drug Effects on Learning and Memory LTP OR improve its effects o Once we know which receptors are necessary for LTP we can manipulate them to stop Antagonists block and slow stop LTP while agonists add to or speed up connections Antagonizing NMDA receptors blocks the induction of LTP no calcium enters so there is really no learning to maintain BUT it does not block the maintenance of LTP memory b c when the antagonist APV is applied after the stimulus it didn t cause EPSP s to drop o NMDA receptors have associative properties when looking at classical conditioning UR neuron is firing and glutamate is being sent from US and CS in coincident activity can allow for predictions now that we have seen a simplistic view of the process Long Term Depression LTD opposite of LTP o Long term decrease in synaptic strength also results due to coincident activity and depends on influx of calcium into the spine can be blocked by AP just like LTP 6 4 15 LTP lecture cont Components important for the induction of


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