The cerebellar interposed nuclei (IN) are an essential part of circuits that control classically conditioned eyeblinks in the rabbit. The function of the IN is under the control of GABAergic projections from Purkinje cells of the cerebellar cortex. The exact involvement of cerebellar cortical input into the IN during eyeblink expression is not clear. While it is known that the application of gamma-aminobutyric acid-A (GABA(A)) agonists and antagonists affects the performance of classically conditioned eyeblinks, the effects of these drugs on IN neurons in vivo are not known. The purpose of the present study was to measure the effects of muscimol and picrotoxin on the expression of conditioned eyeblinks and the activity of IN cells simultaneously. Injections of muscimol abolished conditioned responses and either silenced or diminished the activity of IN cells. Two injections were administered in each picrotoxin experiment. The first injection of picrotoxin slightly modified the timing and amplitude of the eyeblink, produced mild tonic eyelid closure, increased tonic activity of IN cells, and reduced the amplitude of the neural responses. The second injection of picrotoxin abolished conditioned responses, further increased tonic eyelid closure, dramatically elevated the tonic activity of IN cells, and in most cases, abolished neuronal responses. These results demonstrate that both GABA(A)-mediated inactivation and tonic up-regulation of IN cells can interrupt the expression of conditioned eyeblinks and that this behavioral effect is accompanied by the suppression of the neuronal activity correlates of the conditioned stimulus and response.

No abstract

The cerebellar interposed nuclei are considered critical components of circuits controlling the classical conditioning of eyeblink responses in several mammalian species. The main purpose of the present experiments was to examine whether the interposed nuclei are also involved in the control of classically conditioned withdrawal responses in other skeletomuscular effector systems. To achieve this objective, a unique learning paradigm was developed to examine classically conditioned withdrawal responses in three effector systems (the eyelid, forelimb and hindlimb) in individual cats. Trained animals were injected with muscimol in the cerebellar interposed nuclei, and the effects on the three conditioned responses (CRs) were examined. Although the effects of muscimol were less dramatic than previously reported in the rabbit eyeblink preparation, the inactivation of the cerebellar nuclei affected the performance of CRs in all three effector systems. In additional experiments, animals were injected with muscimol at the sites affecting classically conditioned withdrawal responses to determine the effects of these injections on reaching and locomotion behaviors. These tests demonstrated that the same regions of the cerebellar interposed nuclei which control withdrawal reflexes are also involved in the control of limb flexion and precision placement of the paw during both locomotion and reaching tasks. The obtained data indicate that the interposed nuclei are involved in the control of ipsilateral action primitives and that inactivating the interposed nuclei affects several modes of action of these functional units.

No abstract