Ch 8. Synaptic Plasticity 8.9 ~ 8.10 Adaptive Cooperative Systems, Martin Beckerman, Summarized by Kim, S. –J. Biointelligence Laboratory, Seoul National University

2(C) 2009, SNU Biointelligence Lab, Contents 8.9 Neurophysiological basis  Dendritic spines  NMDA and AMPA receptors  The LTP/LTD crossover and the BCM modification threshold 8.10 From genes to behavior  CaM kinase  Griffith Drosophila data  Movement of the BCM threshold  Plastic gates

Dendritic spines  They are small structures found on pyramidal and stellate cells in the neocortex, hippocampus, and other cortical regions.  They serve as a storage site for synaptic strength and help trans mit electrical signals to the neuron's cell body.  The dendrites of a single neuron are variable in size and shape.  As was the case for axonal growth cones, dendritic spines have a dense network of actin filaments, contains actin-activity- mediating proteins such as calmodulin and can change their morphology in res- ponse to signals. 3(C) 2009, SNU Biointelligence Lab,

NMDA and AMPA receptors Both AMPA (α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid) and NMDA (N-methyl D-aspart) receptors are colocated on dendritic spines. AMPA receptors  They allow monovalent cation Na + and K + and divalent cation such as Ca 2+ to move in and out of the dendritic spines.  Their kinetics are fast on the order of millisecond (ms) and are activated by ligand binding. NMDA receptors  It is a specific type of channel-linked glutamate receptor.  They have a slow kinetics that operate on a time scale on the order of 100 ms. 4(C) 2009, SNU Biointelligence Lab,

NMDA and AMPA receptors 5(C) 2009, SNU Biointelligence Lab,

The LTP/LTD crossover and the BCM modification threshold Two major forms of synaptic plasticity, long-term potentiation (LTP) and long- term depression (LTD) are cellular processes involved in learning and memory.  Synaptic plasticity is a process in which synapses change their efficiency as a consequence of their previous activity  Both LTP and LTD can occur at the same synapse in response to different patterns of activation of NMDA receptors.  LTP is a synaptic enhancement that follows high-frequency electrical stimulation in the hippocampus and neocortex  LTD is the weakening of a neuronal synapse that requires Ca 2+ entry through the NMDA receptor. BCM model  BCM theory named for Elie Bienenstock, Leon Cooper and Paul Munro, is a physic -al theory of learning of experience-dependent visual-cortical plasticity in  It assumes that active synapses undergo LTD or LTP depending on the level of postsynaptic response.  It assumes that the value of modification threshold is not fixed, but varies as a function of the previous activity of the postsynaptic cortical neuron. 6 (C) 2009, SNU Biointelligence Lab,

The LTP/LTD crossover and the BCM modification threshold In the BCM model,  The modification threshold in this model floats as a function of the average postsynaptic activity.  A cortical neuron is depolarized below a modification threshold the synaptic strength is increased.  The depolarization is inadequate, the strength is decreased. The experiments by Dudek and Bear  LTD is induced by the low-frequency stimulation.  LTP is induced by the high-frequency stimulation 7 => A plot of change in excitatory postsynaptic potential (EPSP) slope versus freq. of conditioning stimulation is in dramatic agreement with BCM theory.

CaM Kinase Multifunctional Ca 2+ /calmodulin-dependent protein kinase II (CaM kinase) is the most abundant protein kinase in the brain and is highly concentrated in neocortical areas and the hippocampus.  This enzyme phosphorylates a variety of target proteins and mediates many processes triggered by synaptic calcium entry.  It influences neurotransmitter release, membrane excitability, synaptic strength.  In neurons, the property of CaMK autophosphorylation is important for the induction of synaptic plasticity.  In hippocampus, postsynaptic CaMK activity is necessary for generating LTP. 8(C) 2009, SNU Biointelligence Lab,

Griffith Drosophila data Griffith et al. show insights into synaptic and behavioral plasticity.  Drosophila behaviors are regulated by a large number of interacting, multipurpose gene.  In this study, genetic manipulations are carried out in order to  probe the dependence of courting behavior (learning) on CaMK –The result shows removal of CaMK makes the males forgetful. That is, they did not learn at all.  identify the protein targets of CaMK activity –Griffith et al. found eag deficient mutants have learning failure.  The results strengthen the connection between CaMK and the eag protein product.  The downstream target of CaMK phosphorylation is an eag protien that regulates membrane potassium channel outflow. 9(C) 2009, SNU Biointelligence Lab,

Movement of the BCM threshold Studies of crossover point from LTD to LTP by BCM theory  Kirkwood et al. compared visual cortex slices from rats reared in normal visual environments to those raised in the dark.  They provide direct experimental evidence that the value of LTP-LTD crossover point (modification threshold) depends on sensory experience. 10(C) 2009, SNU Biointelligence Lab,  The results show in visual cortex of light-deprived rats that LTP is enhanced and LTD diminished over range of stimulation frequencies and that these effects can be reversed by as little as two days of light exposure.  These support the idea that a variable synaptic modification threshold allows synaptic weight in neural networks to achieve a stable equilibrium. Light-deprived rat (filled symbol) Normal rat (open symbol)