GABA-B RECEPTORS IN THE PARALLEL FIBER PATHWAY OF RAT CEREBELLUM

Binding studies indicate that the molecular layer of the cerebellum has a high concentration of gamma-aminobutyric acid type B (GABA(B)) receptors. In order to elucidate the function of these receptors we have recorded from Purkinje cells in biplanar slices of immature (14-day-old) and adult rat cerebellum using a low-noise, non-invasive, gap technique. The responses of Purkinje cells to parallel fibre stimulation in slices from both immature and adult rats contained a wave that could be inhibited by the GABA(A) antagonist, bicuculline. In slices from immature animals, application of 30-50 muM bicuculline revealed a slow (400 ms to peak) and very long-lasting (up to 1 s) hyperpolarizing wave which was inhibited by GABA(B) antagonists. Activation of GABA(B) receptors on Purkinje cells with an exogenous agonist, baclofen, also generated a hyperpolarization. Baclofen additionally inhibited the synaptic potentials generated in Purkinje cells on stimulating parallel fibres, an effect which could be reversed by GABA(B) antagonists. The potency of baclofen in this respect was similar in adult and immature tissue but another excitatory pathway in the cerebellar cortex, the mossy fibre to granule cell synapse, proved to be much less sensitive. We conclude that, at least in the immature rat, there are GABA(B) receptors on Purkinje cell dendrites and that these receptors can be activated following parallel fibre stimulation; there are also GABA(B) receptors on presynaptic terminals within the molecular layer of immature and adult cerebellum that, when stimulated, inhibit transmitter release.