Non-cholinergic synaptic excitation in neostriatum: pharmacological evidence for mediation by a glutamate-like transmitter.
We studied the synaptic pharmacology of an excitatory pathway in the neostriatum using electrophysiological techniques in tissue slices from rats. In response to single electrical stimuli, two negative, extracellular potentials (N-1 and N-2) were recorded through micropipette electrodes within 150-450 micron 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. 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. 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. gamma-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 microM; (+)-baclofen was 330 times less potent. 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.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010875:Pipecolic Acids / Q000494:pharmacology; D011343:Procaine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013569:Synapses / Q000187:drug effects*
D000927:Anticonvulsants; D005971:Glutamates; D009125:Muscle Relaxants, Central; D018377:Neurotransmitter Agents; D010875:Pipecolic Acids; D018698:Glutamic Acid; C029262:2,3-piperidinedicarboxylic acid; D011343:Procaine; C036615:bicuculline methobromide; D001418:Baclofen; D001640:Bicuculline