Abstract

The neocortex of awake animals is resistant to the induction of long-term synaptic potentiation (LTP). To determine if intense stimulation patterned after the theta (4-12 Hz) electroencephalographic (EEG) rhythm may be effective in inducing synaptic plasticity in the sensorimotor cortex, LTP induction was examined in vivo using single 300-Hz trains and paired trains delivered at a 100-ms interval. Consistent with previous findings, single 300-Hz trains caused a reduction of the early monosynaptic field potential component, reflecting UP of inputs to layer V, and a facilitation of the late polysnaptic component, reflecting the spread of activation across layer V. In response to paired trains, however, there was minimal change in the early component and a much larger increase in the late component as compared to single 300-Hz trains. To investigate the mechanisms mediating the effectiveness of paired trains in inducing UP, an NMDA receptor antagonist was administered and effects on responses to UP induction stimuli and short-pulse trains at theta-frequency were assessed. NMDA-receptor antagonism reduced the early and late component amplitudes and the amount of short-term facilitation observed during repetitive stimulation. This indicates that theta-patterned stimulation induces short-term potentiation effects that involve substantial NMDA-receptor mediated synaptic currents. Therefore, the enhanced induction of UP in the neocortex induced by paired trains versus 300-Hz trains is likely due to enhanced NMDA receptor activation. These results suggest that learning-related plasticity in the sensorimotor neocortex may be promoted by rhythmic, population activity at theta-frequency.