Abstract
The pharmacological properties of excitatory synapses on pyramidal cells in layer V of rat visual cortex were investigated by recording EPSPs intracellularly in tissue slices. The EPSPs were evoked by electrically stimulating cells in layer II/III or axons in white matter. All of the layer V neurons were pyramidal in nature as determined by injections of Lucifer yellow or by electrophysiological criteria. Application of the broadly acting antagonists kynurenic acid and gamma-D-glutamylglycine reversibly antagonized the EPSPs from both presynaptic sources in a dose-dependent manner: 1 and 5 mM kynurenic acid produced 63 and 79% reductions, respectively, of control responses. The specific NMDA antagonist APV (50 microM) caused a small reduction in peak amplitude and a more significant reduction in the duration of the falling phase of EPSPs. When slices were bathed in Mg2+- free medium, the amplitude of the EPSP increased substantially. Under these conditions APV reduced the size of the EPSP to that observed with APV in the presence of 1 mM Mg2+. The voltage sensitivities of the APV- sensitive and APV-insensitive components of the layer II/III-evoked EPSPs were examined. The APV-insensitive component was not voltage dependent and had an extrapolated reversal potential of -10 mV. In contrast, the APV-sensitive component showed an NMDA-like voltage dependency; it was greatest at the most positive potentials tested (-45 mV) and nearly absent at membrane potentials below rest. At potentials near threshold, the APV-sensitive component contributed approximately half of the total response. Although the time to peak and decay were longer for the APV-sensitive component, the latency was the same as that of the APV-insensitive component. These results provide evidence that the layer II/III to V pathway, which comprises a major interlaminar circuit in cortex, is mediated directly through NMDA as well as non-NMDA receptors located on the layer V cells. This finding has implications for the role of this circuit in cortical visual plasticity.