Acquisition of a new-latency conditioned nictitating membrane response--major, but not complete, dependence on the ipsilateral cerebellum.

Abstract

Classical conditioning of the nictitating membrane response (NMR) of rabbits is simple associative learning of a motor response. In several two-stage experiments, reversible inactivations of the deep cerebellar nuclei in stage 1 appeared to prevent acquisition of NMR conditioning in naive rabbits--no conditioned responses (CRs) were evident after inactivations were lifted in stage 2. Results of a three-stage experiment were different. When subjects were first trained with a light conditional stimulus (CS) in stage 1, reversible cerebellar inactivations during conditioning to a different, tone CS during stage 2 did not appear to prevent new learning because CRs to the tone CS were evident when the inactivation was lifted. Results from the two-stage experiments support the suggestion that the cerebellum is essential for the acquisition of NMR conditioning, but results from the three-stage experiment do not. Here, we use a three-stage design with different interstimulus intervals (ISIs) in stages 1 and 2. Because CRs develop with latencies-to-peak dependent on the ISI, learning during stage 1 can be dissociated from that accruing in stage 2. Complete inactivation of the ipsilateral cerebellar nuclei with muscimol substantially but not completely prevented learning with the second ISI during stage 2 because small CR peaks around the stage 2 ISI could be detected in some subjects after the inactivation had been lifted in stage 3. We suggest that the weak levels of conditioning possible during unilateral inactivation depend on the contralateral cerebellum or on extracerebellar circuitry and that these may be capable of supporting transfer of conditioning in a previous three-stage experiment. But, we confirm that normal NMR conditioning is critically dependent on the ipsilateral cerebellum.