Slide 1Neurobiology of memoryProcedural memoryProcedural memoryProcedural memoryProcedural memoryProcedural memoryProcedural memoryInvertebrate models of learningInvertebrate models of learningNonassociative learningNonassociative learningNonassociative learningNonassociative learningAssociative learningAssociative learningAssociative learningAssociative learningVertebrate models of learning and memorySynaptic plasticity in the hippocampusSynaptic plasticity in the hippocampusSynaptic plasticity in the hippocampusSynaptic plasticity in the hippocampusSynaptic plasticity in the hippocampusSynaptic plasticity in the hippocampusSynaptic plasticity in the hippocampusSynaptic plasticity in the hippocampusSynaptic plasticity in the hippocampusSynaptic plasticity in the hippocampusSynaptic plasticity in the hippocampusSynaptic plasticity in the hippocampusSynaptic plasticity in the hippocampusSynaptic plasticity is learning & memorySynaptic plasticity is learning & memoryLong-term memory storageLong-term memory storageLong-term memory storageLong-term memory storageSlide 39MOLECULAR MECHANISMS OF LEARNING AND MEMORYNEUR 3000Dr. Joseph J. NormandinNEUROBIOLOGY OF MEMORY•The neurobiology of memory attempts to understand where and how different types of information are stored•We have seen some examples of “where” being explored•The “how” has also been explored•Hebb suggested that memory results from synaptic modification•Cell assemblies have “strengthened” connections•Invertebrate models: Aplysia californica•Vertebrate models: rodentsPROCEDURAL MEMORY•Procedural memory is amenable to investigation as it does not depend on a model “telling” us what it remembers•These memories are fairly “simple” and can be formed along reflex arcs that link sensation with motor output•Molecular mechanisms may underscore principles that apply to all types of memory formation•We can divide procedural memory into two categories•Nonassociative learning•Associative learningPROCEDURAL MEMORY•Nonassociative learning•A change in behavioral response that occurs over time as a result of a single type of stimulus•Habituation•Learning to ignore a stimulus that lacks meaning•You don’t feel the clothes on your back even though they are stimulating touch sensory neurons•Sensitization•Learning to intensify your response to a stimuli, even those stimuli that were previously benign•You hear a loud bang outside. Just after, your roommate knocks on your door and it causes you to jump out of your seatPROCEDURAL MEMORYPROCEDURAL MEMORY•Associative learning•Forming an association between two previously unrelated events•Classical conditioning•Associate a stimulus that evokes a response* with another stimulus that does not normally provoke that response^•* = unconditional stimulus (US); evokes a unconditional response (UR)•^ = conditional stimulus (CS); requires conditioning (training) to produce a conditioned (learned) response (CR)PROCEDURAL MEMORY•The dog has learned that bell predicts meatPROCEDURAL MEMORY•Associative learning•Instrumental conditioning (operant conditioning)•Learn to associate a response with a meaningful stimulus•Rat has learned that lever-pressing has a consequenceINVERTEBRATE MODELS OF LEARNING•California sea slug or sea hare: Aplysia californicahttp://www.youtube.com/watch?v=ugD4s7mHSsAINVERTEBRATE MODELS OF LEARNING•California sea slug or sea hare: Aplysia californicaNONASSOCIATIVE LEARNING•Habituation of the gill-withdrawal reflex•Repeated stimulation of the siphon with a poke will result in decreased gill withdrawal over time•A sensory neuron from the skin in the siphon projects to motor neurons in the abdominal ganglion•One of those motor neurons is called L7•L7 projects to the muscle of the gill•Where could the memory of habituation be located?NONASSOCIATIVE LEARNING•Habituation of the gill-withdrawal reflex•After habituation there is less neurotransmitter released from the sensory neuron•Ca2+ activation of synaptic vesicles becomes increasingly less effective following habituation•How this happens is unknownNONASSOCIATIVE LEARNING•Sensitization of the gill-withdrawal reflex•A poke on the aplysia siphon will result in a small gill-withdrawal•Applying a shock to the head of the aplysia will result in a large gill-withdrawal•Subsequent pokes (not shocks) to the siphon result in a large gill withdrawal reflex•L29 is sensitive to the head shock and forms a synapse with the axon of the sensory neuron•This enhances the release of NT from the sensory neuron when an action potential makes its way down (from a siphon poke)NONASSOCIATIVE LEARNINGASSOCIATIVE LEARNING•Aplysia can also be classically conditioned•US = shock to the tail, UR = large gill-withdrawal reflex•CS = slight poke to siphon that normally produces almost no gill-withdrawal•After conditioning, a slight poke (CS) resulted in a large gill-withdrawal reflex (CR)•CS must precede the US by <0.5secASSOCIATIVE LEARNINGASSOCIATIVE LEARNING•Aplysia can also be classically conditioned•Remember that L29 activates 5-HT metabotropic receptors in the terminal of the sensory neuron that produced sensitization•Now, this is happening at the same time as an AP hits the sensory neuron terminalASSOCIATIVE LEARNINGVERTEBRATE MODELS OF LEARNING AND MEMORY•Synaptic plasticity, the ability of synapses to change as a function of experience, in widespread throughout the CNS•Recall that the hippocampus is one part of the network involved in declarative memory•Studies in the rodent hippocampus have provided a model of plasticity mechanisms that can be generalized to other brain regions and animalsSYNAPTIC PLASTICITY IN THE HIPPOCAMPUS•Long-term potentiation (LTP): long-lasting enhancement in the strength of a previously stimulated synapse•Long-term depression (LTD): long-lasting reduction in the strength of a previously stimulated synapse•Stimulation of particular pathways in the hippocampus can produce LTP or LTD: plasticity•LTP and LTD interact to form associations (LTP) and those associations can be modified by new inputs (LTD)•A network of cells produces a pattern of synaptic change that is “learning”SYNAPTIC PLASTICITY IN THE HIPPOCAMPUS•The hippocampus is located in the medial temporal lobes on either side of the brain•The hippocampus exhibits well-organized layers of cells•Two sheets of cells folded in
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