Long-lasting facilitation of inhibitory transmission by monoaminergic and cAMP-dependent mechanism in rat cerebellar GABAergic synapses

Roles of monoaminergic neurons in synaptic plasticity are not well clarified at mammalian central synapses. We therefore examined the actions of serotonin and noradrenaline on cerebellar excitatory and inhibitory synapses using the whole-cell recording with rat cerebellar slices. Applications of the two amines selectively elicited long-lasting facilitation of gamma-aminobutyric acid (GABA)-mediated inhibitory transmission, possibly through a presynaptic mechanism. The facilitatory action of the amines on GABAergic transmission was mimicked by forskolin and blocked by protein kinase inhibitors, suggesting the involvement of cyclic AMP (cAMP)-dependent mechanism in their action. A monoamine uptake inhibitor, imipramine, enhanced the GABAergic transmission, whereas it was suppressed by monoamine receptor antagonists, propranolol and methiothepin, suggesting that endogenous monoamines released by stimulation enhance the inhibitory transmission at cerebellar GABAergic synapses in sustained and activity-dependent manner. Such monoaminergic facilitation may provide a likely mechanism for synaptic plasticity in motor coordination within the mammalian cerebellar function.