NMDA- and non-NMDA-receptor components of excitatory synaptic potentials recorded from cells in layer V of rat visual cortex

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.

Use‐dependent changes in synaptic efficacy in rat prefrontal neurons in vitro.

“…Moreover, as expected of a monosynaptic synapse, increasing the extracellular Ca2+ concentration reversed the block caused by the high Mg2+ (Nicholls & Purves, 1970;Berry & Penreath, 1976). We propose that this EPSP recorded in high Mg2+ is monosynaptically evoked, in agreement with the results obtained by Jones & Baughman (1988) (Watkins & Evans, 1981) and CNQX (Honore, Davies, Drejer, Fletcher, Jacobsen, Lodge & Nielsen, 1988) respectively and their voltage dependence when physiological concentrations of Mg2+ are present (Nowak et al 1984;Mayer & Westbrook, 1985). Previous studies have shown that neocortical neurons possess NMDA receptors that can be blocked by APV (Thomson, 1986;Artola & Singer, 1987;Jones & Baughman, 1988;Kimura et al 1989;Sutor & Hablitz, 1989 (Jones & Baughan, 1988) and in the CAI region of the hippocampus (Davies & Collingridge, 1989;Andreasen, Lambert & Jensen, 1989) but differ from those reported in other neocortical regions.…”

“…At all events, any class of inhibitory neurons provides at best a disynaptic input to pyramidal cells since all the afferents arising from the white matter or from the cortico-cortical axons are excitatory (Peters, 1987). Indeed, in the prelimbic cortex (Audinat et al 1989 and the present study) as in other neocortical regions, the IPSP always followed the EPSP (McCormick et al 1985;Avoli, 1986;Thomson, 1986;Connors et al 1988;Jones & Baughman, 1988).…”

“…Zilles (1985)). These neurons were identified as pyramidal cells using criteria previously reported (Penit-Soria, Audinat & Crepel, 1987 (McCormick et al 1985;Avoli, 1986;Jones & Baughman, 1988;Audinat et al 1989). …”

Hippocampal CA1 Circuitry Dynamically Gates Direct Cortical Inputs Preferentially at Theta Frequencies

“…Dendrites in CA1 stratum radiatum contain the highest density of NMDA receptors in the hippocampus, and the voltage sensitivity of these receptors could help boost temporoammonic inputs (Jones and Baughman, 1988;Mel, 1988). Although we do not rule out the possible role of presynaptic disinhibition of GABAergic interneurons at this point, we first assessed the role of NMDA receptors in circuit integration of afferent inputs by determining the effects of perfusion with the NMDA antagonist AP-5 (50 M) during temporoammonic-Schaffer collateral integration experiments.…”

Synaptic transmission in the neocortex during reversible cooling

“…The increase of the input resistance will therefore counteract the effect of decreased driving force on the EPSP amplitude. Finally, the depolarization of the cell enhances activation of NMDA receptor-mediated 23,35,49,50 and other voltage-dependent conductances, 10,21,31,47 which could amplify the EPSP.…”