GABA(B) RECEPTOR ACTIVATION OF PURKINJE-CELLS IN CEREBELLAR SLICES

The metabotropic GABA(B) receptors are densely represented in the mole cular layer of the cerebellar cortex which contains the dendritic tree of the Purkinje cells (PCs). We report here the results obtained by a pplying Baclofen, the specific GABA(B) agonist, to PCs recorded intras omatically in cerebellar slices. Diluted in the perfusion solution or applied by pressure to the molecular layer near to the recorded cell, Baclofen dose-dependently inhibited the PCs as seen by the suppression of Na and Ca dependent action potentials accompanied by a variable me mbrane hyperpolarization. The weak hyperpolarization was interpreted a s due to the dendritic localization of the receptors. These results co ncerned postsynaptic receptor sites since they persisted after bath ap plied TTX blocking presynaptic activity. They also persisted in the pr esence of bicuculline, the GABA(A) antagonist, but they were reduced b y bath application of 2-OH saclofen and CGP55845A, both being GABA(B) receptor antagonists. Current clamp experiments revealed a conductance increase with an equilibrium potential consistent with a K+ channel o pening. The conclusions were reached that GABA inhibition of the PCs i s mediated by GABA(B) receptors in the dendrites and GABA(A) receptors in the soma and dendrites. Therefore, the GABA released by stellate c ells modulate PC activity through two inhibitory mechanisms. (C) 1997 Elsevier Science Ireland Ltd.