A magnesium-sensitive post-synaptic potential in rat cerebral cortex resembles neuronal responses to N-methylaspartate

Abstract

In isolated slices of rat cerebral cortex, intracellular recordings were obtained from pyramidal cells that were predominantly in layers II/III. These cells could be antidromically activated from the underlying white matter and had resting potentials of greater than -75 mV, action potentials with amplitudes of greater than 70 mV (measured from threshold), overshoots of 20-30 mV, and thresholds 20-30 mV positive to the resting potential. The responses of these cells to short (1-2 s) pulses of electrophoretically applied N-methylaspartate (NMA) decreased in amplitude with membrane hyperpolarization between -40 and -120 mV, and were associated with an apparent increase in membrane resistance when recorded in the presence of 1 mM-Mg2+. However, in the absence of Mg2+, responses to NMA increased progressively in amplitude with hyperpolarization and were associated with a decrease in membrane resistance. In addition to conventional excitatory post-synaptic potentials (e.p.s.p.s) and inhibitory post-synaptic potentials (i.p.s.p.s), electrical stimulation of the underlying white matter evoked a novel e.p.s.p. This e.p.s.p. displayed a similar voltage relation to the response evoked by NMA and was associated with an apparent increase in membrane resistance. When Mg2+ was removed from the bathing medium, the properties of the novel e.p.s.p. changed, and it displayed a conventional voltage relation and was associated with a decrease in membrane resistance. In the absence of Mg2+, novel e.p.s.p.s showed potentiation on low frequency repetitive stimulation (0.5-2 Hz). A fully potentiated response could evoke bursts of slow potentials each of which could evoke a burst of fast spikes. In contrast, the more conventional e.p.s.p.s and i.p.s.p.s evoked in pyramidal neurones were unaffected by reducing the Mg2+ concentration from 1.0 to near 0 mM and conventional e.p.s.p.s showed no potentiation on repetitive, low frequency repetition, even after several hours exposure to Mg2+-free medium. The NMA antagonists: 2-amino-5-phosphonovaleric acid, ketamine and cyclazocine, applied electrophoretically at doses that blocked responses to NMA, but which had little effect on responses to glutamate, blocked the novel e.p.s.p. and its potentiation.