lecture 12 LTP - Outline Lecture 12 Review Long Term...

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Outline Lecture 12 Review Long Term Potentiation Molecular Mechanism of Long-term potentiation The Many roles of CaMKII Protein synthesis to support Late-Phase LTP Local protein synthesis Gene Expression Long-Term Depression Problem with a perfect memory
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Hippocampus – Center for Learning and Memory Lomo and Bliss in 1973 discovered if they stimulated a pathway in the hippocampus of a rat there was an increase in synaptic strength that could last for hours to days. This type of synaptic strengthening is called Long-Term Potentiation (LTP). Lomo and Bliss did their experiment on a living rat – today, most people study this phenomena using live slices isolated from a rat or mouse hippocampus. These slices typically only live for a maximum of 10 hours.
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Paradigm that induces LTP Single electrical stimulus = baseline HFS A brief high-frequency period of electrical activity (tetanus) produces an increase in synaptic strength that lasts for hours that could be tested by a single electrical stimulus at later time points.
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Paradigm that induces LTP
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Late phase of LTP is dependent on Protein Synthesis This is known as the Consolidation phase – it is dendentdent on gene expression HFS HFS HFS
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Memory: From Mind to Molecules ; Squire and Kandel Hippocampal slices prepared from this mouse which is missing the catalytic subunit of PKA has reduced Late-LTP Mice have normal early phase LTP (short-term memory). Example of a genetically modified mouse
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Contextual Fear Learning Paradigm Consolidation TRAINING Animal is placed in novel context Receives foot shock New memory is formed ? TEST DAY Animal is returned to same context Test for freezing behavior !@#$ !@#$ de novo transcription and protein synthesis occurs Novel Context is paired with the foot shock. Mice are tested one hour after training (Learning) and 24 hours after training (Consolidation) – measured by “freezing”. Behavioral Test for Memory
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Memory: From Mind to Molecules ; Squire and Kandel Example of a genetically modified mouse Behavioral Test for Memory Transgenic Mouse Forgot ”. Therefore, the memory did not consolidate. Injection of Protein Synthesis inhibtors blocks consolidation! New Protein is required for long-term memory.
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Summary - Properties of LTP Strong activity initiates LTP at active synapses Without initiating LTP at Nearby inactive synapses Weak stimulation alone Does not stimulate LTP When the same weak Stimulus is activated Together with the strong Stimulation of pathway 1 Both sets of synapses are strengthened
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Hebbian Plasticity
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LTP model for the synaptic basis of Hebbian Plasticity HFS – Input A =LTP Then single Stimulus input B = no LTP HFS – Input A =LTP At the same tim: single Stimulus input B = LTP
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NMDA & AMPA Receptors are often at the same synapse Each receptor has it’s own unique physiological properties
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lecture 12 LTP - Outline Lecture 12 Review Long Term...

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