An N-methylaspartate receptor-mediated synapse in rat cerebral cortex: a site of action of ketamine?

It has been proposed that three major receptor subtypes subserve the putative transmitter role of glutamate and aspartate in the mammalian central nervous system. One subtype is classified by the specific agonist N-methylaspartate (NMA) and the specific antagonist 4-amino-2-phosphonovaleric acid. It has been shown recently that excitation of neurones by NMA is also selectively reduced by dissociative anaesthetics such as ketamine and phencyclidine and by sigma opiates, drugs of abuse with common psychotomimetic properties. Responses to NMA have an unusual voltage relation which may result from a voltage-dependent block of the activated channel by physiological concentrations of magnesium. No synaptic potential with properties similar to those of responses to NMA, however, has yet been reported. We describe here an excitatory postsynaptic potential (e.p.s.p.) evoked by electrical stimulation of the white matter and recorded intracellularly from pyramidal cells in slices of rat somatosensory cortex. This e.p.s.p. has the appropriate voltage relation and sensitivity to Mg2+ and ketamine to be an NMA receptor-mediated synapse and a potential central site for the psychotomimetic actions of ketamine.