Long-term Potentiation of Polysynaptic Responses in Layer V of the Sensorimotor Cortex Induced by Theta-patterned Tetanization in the Awake Rat

Although the neocortex in awake, adult animals is resistant to the induction of long-term potentiation (LTP), synaptic potentiation may be enhanced by rhythmic patterns of activation that evoke short- term synaptic facilitation effects. The effectiveness of stimulation patterned after the theta (4-12 Hz) EEG rhythm for the induction of LTP of sensorimotor cortex responses to corpus callosum stimulation was assessed in vivo by inducing LTP using either high- frequency (300 Hz) trains or paired trains delivered at a 100 ms (10 Hz) interval. High-frequency trains caused a reduction of the early field potential component, reflecting a potentiation of direct layer V activation, and a potentiation of the late component, reflecting enhanced polysynaptic activation in layer V. Paired trains resulted in a much larger potentiation of polysynaptic responses than was observed following 300 Hz trains. To determine if short-term facilitation effects contributed to the enhanced LTP induction by theta-patterned trains, facilitation effects induced by the trains were challenged with NMDA receptor antagonists. NMDA-receptor antagonism reduced responses to single pulses, and also reduced facilitated responses evoked by theta-patterned stimulation. The effectiveness of theta-patterned stimulation for the induction of LTP of layer V polysynaptic responses is therefore likely due to frequency-dependent synaptic facilitation effects that enhance NMDA receptor activation.