A biophysical model of bidirectional synaptic plasticity: dependence on AMPA and NMDA receptors.
In many regions of the brain, including the mammalian cortex, the magnitude and direction of activity-dependent changes in synaptic strength depend on the frequency of presynaptic stimulation (synaptic plasticity), as well as the history of activity at those synapses (metaplasticity). We present a model of a molecular mechanism of bidirectional synaptic plasticity based on the observation that long-term synaptic potentiation (LTP) and long-term synaptic depression (LTD) correlate with the phosphorylation/dephosphorylation of sites on the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit protein GluR1. The primary assumption of the model, for which there is wide experimental support, is that postsynaptic calcium concentration and consequent activation of calcium-dependent protein kinases and phosphatases are the triggers for the induction of LTP/LTD. As calcium influx through the n-methyl-d-aspartate (NMDA) receptor plays a fundamental role in the induction of LTP/LTD, changes in the properties of NMDA receptor-mediated calcium influx will dramatically affect activity-dependent synaptic plasticity (metaplasticity). We demonstrate that experimentally observed metaplasticity can be accounted for by activity-dependent regulation of NMDA receptor subunit composition and function. Our model produces a frequency-dependent LTP/LTD curve with a sliding synaptic modification threshold similar to what has been proposed theoretically by Bienenstock, Cooper, and Munro and observed experimentally.
Castellani
G C
GC
Physics Department, CIG and Dimorfipa Bologna University, Bologna 40121, Italy.
Quinlan
E M
EM
Cooper
L N
LN
Shouval
H Z
HZ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006801:Humans; D017774:Long-Term Potentiation; D008954:Models, Biological; D009473:Neuronal Plasticity; D010766:Phosphorylation; D021122:Protein Subunits; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
D021122:Protein Subunits; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D002118:Calcium