Suppression of GABA input by A1 adenosine receptor activation in rat cerebellar granule cells

Abstract Synaptic transmission has been shown to be modulated by purinergic receptors. In the cerebellum, spontaneous inhibitory input to Purkinje neurons is enhanced by ATP via P2 receptors, while evoked excitatory input via the granule cell parallel fibers is reduced by presynaptic P1 (A1) adenosine receptors. We have now studied the modulation of the complex GABAergic input to granule cells by the purinergic receptor agonists ATP and adenosine in acute rat cerebellar tissue slices using the whole-cell patch-clamp technique. Our experiments indicate that ATP and adenosine substantially reduce the bicuculline- and gabazine-sensitive GABAergic input to granule cells. Both phasic and tonic inhibitory components were reduced leading to an increased excitability of granule cells. The effect of ATP and adenosine could be blocked by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), but not by other P1 and P2 receptor antagonists, indicating that it was mediated by activation of A1 adenosine receptors. Our results suggest that, in the cerebellar network, A1 receptor activation, known to decrease the excitatory output of granule cells, also increases their excitability by reducing their complex GABAergic input. These findings extend our knowledge on purinergic receptors, mediating multiple modulations at both inhibitory and excitatory input and output sites in the cerebellar network.