Intracellular recorded synaptic antagonism in the rat dentate gyrus

Abstract

With the exception of acetylcholine at the motoneurone–Renshaw cell synapse, the excitatory chemical transmitters of the major pathways in the vertebrate brain are unknown¹. However, on the basis of biochemical and electrophysiological experiments at the extracellular level, the excitatory acidic amino acids glutamate and aspartate have long been suggested as the most likely candidates for this role^2–4. Unfortunately, difficulties with recording intracellularly from postsynaptic cells at many of these synapses and the lack of selective antagonists have curtailed the criteria by which the identification of glutamate and aspartate as transmitters can be explored. We have now made intracellular recordings from granule cells of the dentate gyrus in vitro and report that γ-D-glutamylglycine (γ-DGG) is an effective antagonist of the excitatory postsynaptic potential (e.p.s.p.) evoked by stimulation of the medial perforant path (PP). During this antagonism the reversal level of the e.p.s.p. remains the same and the passive membrane properties of the postsynaptic membrane are unaltered. Quantal analysis shows that the reduction in the e.p.s.p. amplitude can be accounted for almost entirely by a reduction in quantal size while the quantal content remains unchanged, indicating a direct reduction in the postsynaptic sensitivity to the endogenous transmitter. (±)2-Amino-5-phosphonovalerate (APV) proved to be ineffective as a blocker of the PP-evoked e.p.s.p. and cis-2,3-piperidinedicarboxylate(PDA) caused excitation. The selectivity of γ-DGG and APV against the depolarization induced by the iontophoretic application of N-methyl-D-aspartate (NMDA), quisqualate and kainate closely resembled that in spinal cord. This constitutes the first evidence from a readily identifiable synapse in support of the view that excitatory amino acid receptors of the quisqualate/kainate type are involved in synaptic transmission and offers further support for the suggestion that the endogenous transmitter is aspartate or glutamate.