GABA(A) receptor stimulation blocks NMDA-induced bursting of dopaminergic neurons in vitro by decreasing input resistance

The effects of the GABA(A) agonist, isoguvacine, on NMDA-induced burst firi ng 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 w as insensitive to hyperpolarization by current injection, it was reversibly abolished by the selective GABA(A) agonist, isoguvacine. The block of the rhythmic burst pattern by isoguvacine application occurred regardless of wh ether the chloride reversal potential was hyperpolarizing (ECl- = -70 mV) o r depolarizing (ECl- = -40 mV). In either case, the input resistance of the dopaminergic neurons was dramatically decreased by application of isoguvac ine. It is concluded that GABA(A) receptor activation by isoguvacine disrup ts NMDA receptor-mediated burst firing by increasing the input conductance and thereby shunting the effects of NMDA acting at a distally located gener ator of rhythmic burst firing. (C) 1999 Elsevier Science B.V. All rights re served.