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LTP Long Term Potentiation Long Term Potentiation: • Potentiation: enhancement of one agent by another so that the combined effect is greater than the sum of the effects of each one alone. • In neuroscience, potentiation refers to the persistent strengthening of synapses based on recent patterns of activity. Graph illustrates LTP. Notice the strength of EPSP after potentiation has occurred. Synaptic Plasticity: • Ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity. • Plasticity results from the alteration of the number of neurotransmitter receptors located on a synapse and neurotransmitter production. Synaptic Plasticity: Neurotransmitters: • Endogenous chemicals responsible for synaptic transmission. • Glutamate- (excitatory) plays a key role in LTP, memory, and learning. Receptors: • AMPA (α-amino-3-hydroxy-5-methylisoxazole-4- propionic acid) – Receptor for glutamate – Allows influx of Na+ ions – Produces EPSP • NMDA (N-methyl d-aspartate) – Unblocked (opens) when neuron depolarizes – Allows rapid influx of Ca2+ ions Ca2+ influence on LTP: • Rapid influx of Ca2+ into the postsynaptic neuron triggers the production of several protein kinases including CaMKII, PKC, PKA, and MAPK. • Protein kinases regulate cellular pathways; most importantly signal transduction. CaMKII Protein Kinase Influence on LTP: • Early LTP: – Increase activity of existing AMPA receptors – Insertion of additional AMPA receptors on postsynaptic membrane • Late LTP: – Initiates protein synthesis and gene expression – Increase dendritic spine number, surface area, and synthesis of AMPA receptors. Retrograde Signaling: • Increases release of neurotransmitters by presynaptic neuron. • Requires message from postsynaptic neuron to presynaptic neuron (retrograde) • Messenger: nitric oxide Hippocampus: • Studies of LTP have involved the hippocampus. • Important structure of the brain involved in memory and learning. • Located along the medial surface of the brain. Morris Water Maze: • 1986 Richard Morris tested spatial memory of rats by pharmacologically modifying their hippocampus. • Rats with NMDA receptors blocked were significantly impaired.