We have investigated the role of the N-methyl-D-aspartate (NMDA) receptor, a subtype of glutamate receptor, in the responses of cells in adult cat visual cortex. After intracortical infusion of the NMDA receptor antagonist DL-2-amino-5-phosphonovalerate (DL-APV) for one day, iontophoretic responses to NMDA, to kainate, and to quisqualate revealed a receptor blockade specific to NMDA receptors and extending several millimeters from the cannula. In this region, neuronal responses to visual stimulation were profoundly suppressed, in a manner strongly correlated with the degree ofNMDA receptor blockade. Neither NMDA receptor blockade nor activity suppression was caused by the inactive stereoisomer L-APV. Hence, we conclude that NMDA receptors make a major contribution to normal excitatory transmission in adult visual cortex. We have studied the role of the NMDA receptor in excitatory synaptic transmission in visual cortex. Previous reports (12, 13) have concluded that NMDA receptors contribute to excitatory transmission in the visual cortex of young kittens during the critical period for synaptic plasticity, but that they do not do so appreciably in adult cats. To study the role of NMDA receptors in cortical synaptic transmission, several conditions must be achieved. First, one needs to produce a blockade of NMDA receptors which is uniform at least over the full extent of an individual cell's synaptic input. Second, one must be able to assess the degree and the specificity of NMDA blockade at each cortical site studied. Then one may assess the effect of that blockade on spontaneous and visually driven activity.To achieve a locally uniform blockade, we have chronically infused the cortex with the NMDA-receptor-blocker 2-amino-5-phosphonovalerate (APV). We found that APV infusion created a specific blockade of NMDA receptors over several millimeters of cortex. In this region, neuronal responses to visual stimulation were profoundly suppressed, in a manner strongly correlated with the degree of NMDA blockade. We interpret these results to suggest that visual responses, in at least a critical subset of visual cortical cells, depend on a slow EPSP mediated by activation of NMDA receptors in response to high-frequency sensory input. An abstract of this work has appeared (14).
MATERIALS AND METHODSIn six adult cats a 33-gauge cannula (200 Im outer diameter) was implanted under aseptic conditions 2 mm below the cortical surface into the representation of the central visual fields of one hemisphere of primary visual cortex (HorsleyClarke coordinates AP -1-0, LM 2). The cannula was attached to an osmotic minipump (Alza 2001) delivering 1 pul/hr of 50 mM (pH 7.2-7.6) DL-APV (four animals) or of the active stereoisomer, D-APV (two animals). Opposite hemispheres were either left untreated (three animals) or implanted with a cannula delivering saline (one animal) or the inactive stereoisomer, L-APV (two animals). APV infusions continued throughout the recording sessions. Five ofthese animals were used to study visually ev...