GABAB Receptors in the Parallel Fibre Pathway of Rat Cerebellum


Professor J. Garthwaite, Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3BS, UK


Binding studies indicate that the molecular layer of the cerebellum has a high concentration of γ-aminobutyric acid type B (GABAB) 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 GABAA antagonist, bicuculline. In slices from immature animals, application of 30–50 μM bicuculline revealed a slow (400 ms to peak) and very long-lasting (up to 1 s) hyperpolarizing wave which was inhibited by GABAB antagonists. Activation of GABAB 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 GABAB 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 GABAB receptors on Purkinje cell dendrites and that these receptors can be activated following parallel fibre stimulation; there are also GABAB receptors on presynaptic terminals within the molecular layer of immature and adult cerebellum that, when stimulated, inhibit transmitter release.