Acta Pharmacologica Sinica (2009) 30: 141-152; doi: 10.1038/aps.2008.18; published online 5th January 2009

Involvement of the ipsilateral and contralateral cerebellum in the acquisition of unilateral classical eyeblink conditioning in guinea pigs

Aim: The aim of this study was to evaluate the relative contributions of the ipsilateral and contralateral cerebellum to the acquisition of unilateral classical eyeblink conditioning (EBCC).

Methods: The unilateral EBCC was achieved using a binaural tone conditioned stimulus (CS) paired with a left airpuff unconditioned stimulus (US).  A high-resolution potentiometer was used to monitor eyeblink responses.  Guinea pigs received one CS-US session followed by three CS-US sessions (sessions 2 to 4), during which microinjections of muscimol, a GABA_A receptor agonist, were performed to reversibly inactivate the cerebellum unilaterally prior to training.  To test whether any learning had occurred during these inactivation sessions, training was continued for six more CS-US sessions (sessions 5 to 10) without any inactivation. 

Results: Animals with inactivation of the left cerebellum had no signs of left conditioned response (CR) during sessions 2 to 4, and their CR acquisition during sessions 5 to 10 was not distinguishable from that of control animals during sessions 2 to 7.  In contrast, animals with inactivation of the right cerebellum acquired left CRs during sessions 2 to 4, although their CR acquisition was significantly retarded during session 2.  In addition, microinjections of muscimol into the right cerebellum did not affect left neuro-behavioral activity.  Finally, microinjections of muscimol into either the left or the right cerebellum did not affect the performance of tone-airpuff evoked unconditioned response (UR). 

Conclusion: In contrast to the essential role of the ipsilateral cerebellum, the contralateral cerebellum is potentially involved in the acquisition of unilateral EBCC during the early stage of training.

Keywords: eyeblink; classical conditioning; acquisition; muscimol; deep cerebellar nuclei; cerebellar cortex