GABA(B) receptor activation of Purkinje cells in cerebellar slices

The metabotropic GABA(B) receptors are densely represented in the molecular layer of the cerebellar cortex which contains the dendritic tree of the Purkinje cells (PCs). We report here the results obtained by applying Baclofen, the specific GABA(B) agonist, to PCs recorded intrasomatically 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 membrane hyperpolarization. The weak hyperpolarization was interpreted as due to the dendritic localization of the receptors. These results concerned postsynaptic receptor sites since they persisted after bath applied TTX blocking presynaptic activity. They also persisted in the presence of bicuculline, the GABA(A) antagonist, but they were reduced by 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 opening. The conclusions were reached that GABA inhibition of the PCs is mediated by GABA(B) receptors in the dendrites and GABA(A) receptors in the soma and dendrites. Therefore, the GABA released by stellate cells modulate PC activity through two inhibitory mechanisms.