Non‐cholinergic synaptic excitation in neostriatum: pharmacological evidence for mediation by a glutamate‐like transmitter

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Abstract
1 We studied the synaptic pharmacology of an excitatory pathway in the neostriatum using electrophysiological techniques in tissue slices from rats. 2 In response to single electrical stimuli, two negative, extracellular potentials (N-1 and N-2) were recorded through micropipette electrodes within 150–450 μm of the stimulating cathode. N-2 was reversibly reduced or abolished by reducing the concentration of calcium in the bathing medium, while N-1 was unaffected. Both N-1 and N-2 were reversibly abolished by the local anaesthetic procaine. 3 Single-unit, extracellular action potentials were, at times, associated with either N-1 or N-2. Intracellular recordings showed action potentials at N-2 latency arising from graded, monophasic, depolarizing potentials. 4 Bath-applied cholinoceptor and dopamine receptor antagonists failed to reduce N-2. By contrast, antagonists of excitatory amino acid transmitters reversibly reduced or abolished N-2. γ-d-Glutamylglycine (GG), (±)-cis-2,3-piperidine dicarboxylic acid (PDA) and dL-2-amino-4-phosphonobutyric acid (APB) blocked N-2 with ED50s of 0.79 mm, 1.0 mm and 1.1 mm, respectively. (−)−Baclofen reversibly blocked N-2 with an ED50 of 0.79 μm; (+)-baclofen was 330 times less potent. 5 The results suggest that N-1 results from direct activation of fibre tracts or cell bodies, while N-2 is a population spike mediated by excitatory synapses whose natural transmitter pharmacologically resembles glutamate.