Lecture 17.docx

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

 Slide 13  Explicit memory – information that you can recall  Implicit memory – can’t really tell another person using in a narrative form but you can show through seq of motor output o Associative (classical and operant conditioning) o Non-associative memory: 2 types: habituation and sensitization  These are served by reflex pathways in the spinal cord  Motor behaviours  Brain mapping the diff parts that subserves diff kinds of memories  Semantic memory and episodic memory are subserved/processed in the medial, temporal lobe including hippo and parts of the diencephalon  Procedural -> motor related structure: basal ganglia, cerebellum , primary motor area and supplementary motor area  Working memory – prefrontal cortex   Habituation and sensitization  We’ve all experienced it  Sensitization: increase in response to a naturally weak stimulus after being presented with a strong stimulus o Eg. doctor’s office for vaccination  Habituation: decline in the response after repeated exposure to the same stimulus o Not so meaningful stimulus and your response declines progressively   Invertebrate models used to find molecular mechanisms  Popular model: aplysia (sea slug)  Neuroscientists have focused on a reflex behaviour: siphon/gill withdrawal reflex  Touch parts of the aplysia -> siphon and gill are sensitive -> structures get internalized  Mediated by a simple circuit: sensory neuron innervates the motor neuron responsible for the withdrawal   Habituation: decline in response to a stimulus after repeated exposure  Organism learns to ignore the stimulus  Evolutionary significance? Don’t waste energy on irrelevant stimuli  Gill will withdraw; respond strongly;  After several exposures to this not so strong stimulus, you will eventually lead to a decrease in the quantities of neurotransmitters being released in the terminals  Mechanism for the decrease? Not fully explained yet o One: inactivation of Ca channels (usually follows a time course) -> decrease of nt -> decrease in reaction   In vertebrates, such as frogs, you can electrophysiogically demonstrate how habituation happens  These researchers used a piece of muscle from the frog and bathed it in high conc of Ca and then measured the changes in end plate potential of the muscle in response to repeated stimulation  B -> example of what happens in habituation -> synaptic depression  Initially stimulate muscles -> high amplitude  Stimulate again, you can see it progressively decrease  This decrease in end plate potential can stay for long periods of time, a max of 10s   Sensitization: increase in the response to a gentle stimulus after exposure to a strong stimulus (like electric shock)  What happens in the circuitry is more complicated than habituation  Intracellular events progress   Illustration of diff parts of the aplysia  Strong stimulus: electric shock to the tail -> activates a specific pathway  Naturally, a strong response  Record post synaptic activity -> very high amplitude  After exposing it to an electric shock and then wait for awhile and then apply a gentle touch on the siphon  Initially, the gentle touch doesn’t lead to a strong gill withdrawal reflex but because it was followed by a strong stimulus to the tail, touching the siphon will lead to a withdrawal response as strong as the response to the electrical shock  Why?  This pathway strengthens the synaptic connections   Mechanism occurs in the synapse  This is a facilitating neuron (interneuron) that is being stimulated by the sensory neuron that receives information from the electric shock  The interneuron releases a neurotransmitter, serotonin which is excitatory and it synapses onto the axon of the sensory neuron that mediates the siphon response  What does it do to the siphon axon terminal? It strengthens it.  How? There’s a series of intracellular cascades that mediate this strengthening  Apply electric shock -> increase activity of the interneuron -> serotonin is released onto the presynaptic axon of the sensory neuron mediating the siphon response  Serotonin binds to its receptors -> activate G proteins, adenylyl cyclase which increases the conversion of cyclic AMP  cAMP is a secondary messenger -> activates protein kinase a -> phosphorylates and blocks voltage gated K channels  you touch the siphon -> generate an AP running off to these pre syn axon -> activation of gill  AP reaches the presyn axon, AP stays longer because no K to restore membrane potential  K efflux in response to increase in AP -> termination of the AP; block this -> prolong AP  Enhanced release of neurotransmitter, leading to the motor neuron having a strong withdrawal  This type of synaptic process -> presynaptic facilitation  Because activity of the presynapse is facilitated by another synapse  Non-Hebbian learning aka heterosynaptic learning (2 synapses involved)   Learning  In the brain, it’s more complex than reflex of course  It’s not sufficient just to have one strong event  Synaptic changes subserving learning and memory involves changes in the pattern of firing of the presynaptic neuron  1 AP is not enough  In sensitization and habituation, just 1 stimulus is sufficient  In the brain, the post synaptic activity depends on the ongoing pattern of the presynaptic potential activity; freq of firing  So you will likely learn/consolidate information into LTM if you stimu
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