Reversible inactivation of the cerebellar interpositus nucleus completely prevents acquisition of the classically conditioned eye-blink response.

Numerous studies from several laboratories report that temporary inactivation of the cerebellar interpositus nucleus and regions of overlying cortex during eye-blink conditioning completely prevents acquisition of the conditioned eye-blink response (CR) without affecting the ability to learn the CR in subsequent training without inactivation. Recently, these results have been challenged by the suggestion that learning was not completely blocked in these studies. Instead, it has been suggested that low levels of responses on test sessions might represent a retarded form of learning caused by drug effects on cerebellar cortex. The present study was designed to address this issue directly. Very low doses of muscimol were used to selectively inactivate the interpositus nucleus of rabbits during five conditioning sessions. Animals performed no significant levels of CRs during those sessions. Training was continued four more sessions without any inactivations to test whether any learning had occurred during the previous five sessions. Detailed analysis of responses during session six revealed that learning was completely blocked by the low doses of muscimol infused into the interpositus during the first five sessions. Animals subsequently acquired the CR normally. These results confirm and extend the original findings that appropriate lesions (either temporary or permanent) of the interpositus nucleus completely prevent acquisition of the conditioned eye-blink response. Other issues regarding reversible inactivation studies are also discussed.