Phase Sensitivity of Synaptic Modifications in Oscillating Cells of Rat Visual Cortex

Synaptic modifications depend on the amplitude and temporal relations of presynaptic and postsynaptic activation. The interactions among these variables are complex and hard to predict when neurons engage in synchronized high-frequency oscillations in the β and γ frequency range, as is often observed during signal processing in the cerebral cortex. Here we investigate in layer II/III pyramidal cells of rat visual cortex slices how synapses change when synchronized, oscillatory multifiber activity impinges on postsynaptic neurons during membrane potential (Vm) oscillations at 20 and 40 Hz. Synapses underwent long-term potentiation (LTP) when EPSPs coincided with the peaks of the Vm oscillations but exhibited long-term depression (LTD) when EPSPs coincided with the troughs. The induction of LTP but not of LTD was NMDA receptor dependent, required additional activation of muscarinic receptors in older animals, and persisted in a kainate-driven increased conductance state. Thus, even when neuronal networks engage in high-frequency oscillations, synaptic plasticity remains exquisitely sensitive to the timing of discharges. This is an essential prerequisite for theories which assume that precise synchronization of discharges serves as signature of relatedness in distributed processing.