1. Ch 8. Synaptic Plasticity 8.9 ~ 8.10 Adaptive Cooperative Systems, Martin Beckerman, 1997. Summarized by Kim, S. –J. Biointelligence Laboratory, Seoul National University http://bi.snu.ac.kr/

2. 2(C) 2009, SNU Biointelligence Lab, http://bi.snu.ac.kr/ Contents 8.9 Neurophysiological basis  8.9.1 Dendritic spines  8.9.2 NMDA and AMPA receptors  8.9.3 The LTP/LTD crossover and the BCM modification threshold 8.10 From genes to behavior  8.10.1 CaM kinase  8.10.2 Griffith Drosophila data  8.10.3 Movement of the BCM threshold  8.10. 4 Plastic gates

3. 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, http://bi.snu.ac.kr/http://bi.snu.ac.kr/

4. 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, http://bi.snu.ac.kr/http://bi.snu.ac.kr/

5. NMDA and AMPA receptors http://www.sumanasinc.com/webcontent/animations/content/receptors.html 5(C) 2009, SNU Biointelligence Lab, http://bi.snu.ac.kr/http://bi.snu.ac.kr/

6. 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 1981.  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, http://bi.snu.ac.kr/http://bi.snu.ac.kr/

7. 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.

8. 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, http://bi.snu.ac.kr/http://bi.snu.ac.kr/

9. 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, http://bi.snu.ac.kr/http://bi.snu.ac.kr/

10. 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, http://bi.snu.ac.kr/http://bi.snu.ac.kr/  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)