Evidence for a specific role for cortical NMDA receptors in slow-wave sleep.

Iontophoresis of the N-methyl-D-aspartic acid (NMDA) receptor antagonist 2-amino-5-phosphonovaleric acid (2-APV) was found to suppress spontaneous bursting activity of layer V cortical neurones during stage 3/4 sleep in unrestrained, normally behaving rats. Iontophoresis of NMDA, on the other hand, increased cortical burst durations and increased the number of spikes per burst. 2-APV was found not to alter cells' responses to tactile stimulation or the generation of neuronal spindling activity during stage 2 sleep. These results provide the first evidence that NMDA receptors subserve a specific function in the neocortex of the behaving animal, by gene-rating burst activity in cortical neurones during stage 3/4 of the natural sleep state. The activation of NMDA/2-APV-sensitive cortical receptors by afferents from the anterior intralaminar nuclei in the generation of bursts by cortical cells during stage 3/4 sleep is discussed.