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April 3rd 2012.docx

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Dalhousie University
NESC 2570
Stefan Kreuger

April 3rd 2012 April-03-12 11:33 AM The rodent hippocampus  We know that the hippocampus is critically involved in the formation of declarative memories (memories about things) o Learning facts, statements, ect. o Motor memories (bike riding) not formed here HM o Young man in the 1950s who had epilepsy, suffered from life threatening seizures, had neurosurgical isolation performed, isolating his hippocampus from the rest of his brain o Suppressed any further seizures from occurring, however had bad side effect o Was only able to remember things that happened before his surgery, however was not able to form any declarative memories anymore o So not all kinds of memories eliminated, just his declarative ones For several pathways in hippocampus, if you gave high frequency train of stimulation, you would see increased strength in the responses. Regions of the neocortex (entorhinal cortex, almost all regions of neocortex project into here) project into the hippocampus through the perforant path  They project onto granule cells (in the dentate gyrus)  Which project onto CA3 pyramidal cells (CA3 zone)  Which then project onto CA1 pyramidal cells, (CA1 zone)  And then back into neocortex All these synapses use glutamate, therefore all excitatory   All these synapses combine to create a memory forming machine Tim Bliss and Terje Lomo  Did research on the synapse that CA3 neurons make onto CA1 neurons  That pathway is referred to as Schaffer collaterals  What they did in their experiments, is they recorded synaptic responses in CA1 cells, and these responses were evoked by stimulating the axons in the Schaffer collateral o Responses were fairly uniform from stimulus to stimulus when stimulating every 30ish seconds o But if they gave a second of stimulation at 100 per second, and then fired at the normal speed again  The response had increased, (post-tetanic potentiation)  This response lasted for weeks after the original high frequency change on stimulation  Showed a very long lasting form of synaptic plasticity  Lomo identified that this long term change of plasticity in the synapse could be exactly what you want to be able to form memory  *only the pathway they stimulated was affected* o If they stimulated pathway 1, pathway 2 was unaffected in terms of its response strength to the stimulation every 30 seconds o Shows a great deal of specificity o However if you give strong stimulation to pathway 1, and weak stimulation to pathway 2 (would not normally fire action potential), pathway 2 would show associative LTP, crucial method in associative learning  Named the type of potentiation they observed Long Term Potentiation (LTP) Another way to get LTP  Pairing presynaptic stimulation, with postsynaptic action potential generation for a few times over a couple minutes revealed LTP afterwards when stimulating just the presynaptic neuron o See rule in slide by Hebb  Timing of coincidence between presynaptic stimulation and postsynaptic firing is crucial to this process  If the presynaptic stimulus came right before the postsynaptic action potential like in nature, strong LTP observed, but if postsynaptic action potential fired before presynaptic stimulus, depression is observed o As separation time increases between stimulations, the effect is weakened How can synaptic plasticity achieve associative memory  Assuming all synapses are Hebbian synapses  Imagine visual cues are of appetizing looking food that make you salivate o All visual cues weighted as 1 (str
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