Kir3 channel blockade in the cerebellar cortex suppresses performance of classically conditioned Purkinje cell responses

In the eyeblink conditioning paradigm, cerebellar Purkinje cells learn to respond to the conditional stimulus with an adaptively timed pause in its spontaneous firing. Evidence suggests that the pause is elicited by glutamate released from parallel fibers and acting on metabotropic receptors (mGluR7) which initiates a delayed-onset suppression of firing. We suggested that G protein activation of hyperpolarizing K(ir)3 channels (or ‘GIRK’, G protein-coupled inwardly-rectifying K(+) channels) could be part of such a mechanism. Application of the K(ir)3 antagonist Tertiapin-LQ locally in the superficial layers of the cerebellar cortex in decerebrate ferrets suppressed normal performance of Purkinje cell pause responses to the conditional stimulus. Importantly, there was no detectable effect on spontaneous firing. These findings suggest that intact functioning of K(ir)3 channels in the cerebellar cortex is required for normal conditioned Purkinje cell responses.