Excessive glutamate as an inhibitor of excitatory transmission in rat hippocampal slice.

Exposure of rat hippocampal slices to perfusate containing 1-2 mM glutamate (GLU) induces reversible and relatively selective blockade of excitatory transmission. Intracellular recordings from 20 region CA1 hippocampal cells demonstrated only transient and mild effects on resting membrane properties and action potentials. In contrast, in 2 mM GLU excitatory postsynaptic potentials declined to 28% of control (P less than 0.001); inhibitory postsynaptic potentials remained robust at 88% of control. This suggests that excess exposure to GLU may result in a selective 'down-regulation' of excitatory synaptic transmission, while preserving inhibitory pathways. These observations may have practical implications for development of new anticonvulsant drugs.