Activation of Cerebellar B-type γ-aminobutyric Acid Receptor Modulates Optokinetic Reflex Adaptation

Abstract

The cerebellar cortex, the brain region responsible for motor coordination and learning expresses a high density of B-type γ-aminobutyric acid receptor (GABAbR). Previous in vitro and in situ studies indicated that cerebellar GABAbR may mediate multiple forms of inhibitory and excitatory modulation of cerebellar circuits. Nevertheless, the in vivo influence of cerebellar GABAbR activation is unclear. As the first step in addressing this issue, we examined how pharmacological activation of cerebellar GABAbR modulates optokinetic reflex (OKR), an involuntary cerebellum-dependent eye movement for stabilizing the retinal image against the drift of the visual scene. We injected baclofen, a GABAbR-selective agonist, or control saline into the cerebellar flocculi of adult mice and then performed 1-h OKR measurement sessions on two consecutive days. In the day 1 session, the baclofen (5 nM)-injected mice and control mice showed similar initial OKR gains and similar training-induced increases in the OKR gain (OKR adaptation). This result suggests that GABAbR activation does not affect cerebellar computation for executing OKR and formation of short-term memory for OKR adaptation. At the beginning of the day 2 session, the baclofen (5 nM or 50 μM)-injected mice showed an OKR gain higher than that achieved in the day 1 session while the control mice did not. This result suggests that GABAbR activation may facilitate the formation of OKR adaptation-related long-term memory. These findings provide a new insight into the functional architecture of the cerebellar circuits and indicate GABAbR to be a new target of pharmacological therapy against diseases with cerebellar dysfunction.