title: Non-cholinergic synaptic excitation in neostriatum: pharmacological evidence for mediation by a glutamate-like transmitter.
abstract: 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.
mesh_terms: 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*
chemical_list: 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