How feedback inhibition shapes spike-timing-dependent plasticity and its implications for recent Schizophrenia models

It has been shown that plasticity is not a fixed property but, in fact, changes depending on the location of the synapse on the neuron and/or changes of biophysical parameters. Here, we investigate how plasticity is shaped by feedback inhibition in a cortical microcircuit. We use a differential Hebbian learning rule to model spike-timing-dependent plasticity and show analytically that the feedback inhibition shortens the time window for LTD during spike-timing-dependent plasticity but not for LTP. We then use a realistic GENESIS model to test two hypothesis about interneuron hypofunction and conclude that a reduction in GAD67 is the most likely candidate as the cause for hypofrontality as observed in Schizophrenia. (C) 2011 Elsevier Ltd. All rights reserved.