Lecture 19.docx

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University of Toronto St. George
Cell and Systems Biology
Francis Bambico

Review  Associative LTP: storage of new information -> establishing new synapses;  Key components: need 2 stimuli, 2 axons or more; principle of cooperativity  Objective: in order to sufficiently depolarize the PS neuron -> open NMDA receptors (dislodge Mg)  Need additional axons to help  Ca influx through NMDA receptors is important in maintaining conc of Ca in PS neuron -> activate several types of biochemical pathway  Early phase of LTP: protein kinase (calcium calmodium protein kinase 2) which leads to insertion of new AMPA receptors (usually floating in the cytosol); new AMPA receptors -> desired increase in synaptic efficacy o Test it by apply test stimulus in the initially weak stimulus (now stronger because more receptors inserted) -> now a strong response o Glutamate release is the same as before; will bind to more AMPA and NMDA receptors -> increase Ca influx  Late LTP: consolidation of LTM but you will eventually forget it but it will linger and last longer than STM but if you want it to be permanently stable -> adenylyl cyclase, MAP kinase, irk? -> phosphorylation of transcription factors -> gene transcription -> increase in proteins needed to make more synapses -> information will linger for longer periods of time  Really not clear whether associative LTP is what causes LTM storage but it’s a hypothesis  So far, we’ve talked about LTP in hippocampus  LTP also occurs in many other parts of the brain thus subserving many other types of learning and memory  Hippocampus - Declarative, episodic, somatic memory are stored in LTM  Procedural or implicit types of memories are ones we’re not conscious about obtaining or learning  Procedural, Classical and operant conditioning, priming  These types of implicit memories is subserved in other structures of the brain including striatum for procedural memory (skills, habits) and other parts of the motor cortices Slide 19  Conditioning takes place in cerebellum and amygdala  After several pairings of sound from the computer with food, just the sound without the food is sufficient to illicit a hunger response; Association between 2 stimuli; one is weak –> the sound : classical conditioning  In his experiments, he had a dog with an unconditioned stimulus and illicits a strong salivary response; another stimulus that does not naturally illicit a strong response; during conditioning, unconditioned stimulus and conditional neutral stimulus and then after several trials, the weak stimulus ilicits a strong response eventually  Neutral stimulus can be anything that doesn’t naturally produce a natural response  But if you pair them for many trials and after just present neutral stimulus -> strong physiological response  How does classical conditioning occur? The neutral stimulus is a touch/brush of the aplysia which will illicit a not so strong response; electric shock to the tail -> strong stimulation -> lots of neurotransmitters -> serotonin ->> activation of the motor neuron -> strong gill withdrawal reflex  If I pair a neutral stimulus just before the electric shock on the tail several times and then record the response of the motor neuron and gill withdrawal reflex after that conditioning trial in response to the mantle shell  Apply brush without electric shock and that will produce a strong response, as strong as the one ilicited by the electric shock  This is trace of PSP recorded from motor neuron before the conditioning in response to neutral stimulus – not that strong  After conditioning and pairing with electric shock, record PSP -> increase in amplitude of PSP of the motor neuron  Example of classical conditioning in aplysia  why did the mantle shell obtain a stronger response after pairing of the stimulus?  What actually happens is that when you apply to mantle shell just before tail shock, you are already stimulating the motor neurons  While motor neuron is already being stimulated, you immediately present the electric shock -> activation of seratonergic interneuron that lead into stimulation of presynaptic axon further releasing neurotransmitters while the motor neuron is already active ->
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