LONG-LASTING FACILITATION OF INHIBITORY TRANSMISSION BY MONOAMINERGICAND CAMP-DEPENDENT MECHANISM IN RAT CEREBELLAR GABAERGIC SYNAPSES

Roles of monoaminergic neurons in synaptic plasticity are not well cla rified at mammalian central synapses. We therefore examined the action s of serotonin and noradrenaline on cerebellar excitatory and inhibito ry synapses using the whole-cell recording with rat cerebellar slices. Applications of the two amines selectively elicited long-lasting faci litation of gamma-aminobutyric acid (GABA)-mediated inhibitory transmi ssion, possibly through a presynaptic mechanism. The facilitatory acti on of the amines on GABAergic transmission was mimicked by forskolin a nd blocked by protein kinase inhibitors, suggesting the involvement of cyclic AMP (cAMP)-dependent mechanism in their action. A monoamine up take inhibitor, imipramine, enhanced the GABAergic transmission, where as it was suppressed by monoamine receptor antagonists, propranolol an d methiothepin, suggesting that endogenous monoamines released by stim ulation enhance the inhibitory transmission at cerebellar GABAergic sy napses 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.