GABAA receptor stimulation blocks NMDA-induced bursting of dopaminergic neurons in vitro by decreasing input resistance.
The effects of the GABAA agonist, isoguvacine, on NMDA-induced burst firing of substantia nigra dopaminergic neurons were studied with intracellular and whole cell recordings in vitro. NMDA application caused the neurons to fire in rhythmic bursts. Although the NMDA-induced bursty firing pattern was insensitive to hyperpolarization by current injection, it was reversibly abolished by the selective GABAA agonist, isoguvacine. The block of the rhythmic burst pattern by isoguvacine application occurred regardless of whether the chloride reversal potential was hyperpolarizing (ECl-=-70 mV) or depolarizing (ECl-=-40 mV). In either case, the input resistance of the dopaminergic neurons was dramatically decreased by application of isoguvacine. It is concluded that GABAA receptor activation by isoguvacine disrupts NMDA receptor-mediated burst firing by increasing the input conductance and thereby shunting the effects of NMDA acting at a distally located generator of rhythmic burst firing.
Paladini
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CA
Aidekman Research Center, Center for Molecular and Behavioral Neuroscience, Program in Cellular and Molecular Biodynamics, Rutgers, The State University of New Jersey, 197 University Ave., Newark, NJ 07102, USA.
Iribe
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Y
Tepper
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JM
D000818:Animals; D004298:Dopamine / Q000502:physiology; D004553:Electric Conductivity; D017097:Electric Impedance; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018755:GABA Agonists / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D066298:In Vitro Techniques; D007539:Isonicotinic Acids / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013268:Stimulation, Chemical
D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D007539:Isonicotinic Acids; D016194:Receptors, N-Methyl-D-Aspartate; D004298:Dopamine; C015300:isoguvacine