Compartmentation of the rabbit cerebellar cortex.

The cytoarchitecture of the adult rabbit cerebellum is revealed by using zebrin II/aldolase c immunocytochemistry in both wholemount and sectioned material. Zebrin II is expressed by approximately half of the Purkinje cells of the cerebellar cortex. In most regions these form a symmetrical array of zebrin II positive and negative parasagittal bands. Four transverse expression domains are identified in the vermis: (1) an anterior zone, comprising four narrow bands, one at the midline and three laterally to either side, extending throughout the anterior lobe to the primary fissure; (2) a central zone with broad immunoreactive bands separated by narrow zebrin II negative bands that disappear caudally to leave no apparent compartmentation; (3) a posterior zone with prominent alternating zebrin II positive and negative bands; and (4) a nodular zone in which all Purkinje cells express zebrin II. In the hemispheres a striped topography is found in lobules HVI, HVII, and crus I, and all Purkinje cells are zebrin II+ in the flocculus and paraflocculus. Because of its importance for the classical conditioning of the eyeblink response, we made a detailed analysis of lobule HVI of the hemisphere. The immunocytochemical data show a complex substructure within HVI with three prominent zebrin II positive bands (probably homologous with P4a+, P4b+, and P5+ of rodents) separated by two zebrin II negative regions (P4- and P4b-). Thus, the organization of the rabbit cerebellum is consistent with the patterns described previously for rat, mouse, and opossum and suggests that there may be a common ground plan for the mammalian cerebellum.

Cerebellar mechanisms in eyeblink conditioning.

A recent model of cerebellar learning in eyeblink conditioning predicts two sites of plasticity, the cerebellar cortex and cerebellar nuclei, which store information relating to timing and driving the movement, respectively. Consistent with this idea, lesions of the cortex or reversible "disconnections" of Purkinje cell output to the nuclei have been shown to disrupt response timing to produce short-latency conditioned eyeblinks. To better characterize potential cortical and nuclear plasticities, we analyzed the effects upon nictitating membrane (NM) and eyeblink conditioned responses (CRs) of different drugs administered to the cortex and to the nuclei. When either excitatory or inhibitory inputs to the cerebellar cortical lobule HVI were blocked by infusions of the AMPA receptor antagonist CNQX or the GABA-A receptor antagonists picrotoxin or SR95531, CRs were abolished. Similarly GABA-A receptor antagonists in the cerebellar nuclei abolished CRs. CR latencies were never shortened. However, blockade of AMPA/kainate receptor-mediated excitatory transmission to the nuclei had no effect upon CR frequencies or latencies. These results suggest that normal cortical and nuclear function is required for performance of NM and eyeblink CRs. We saw no evidence that CRs can be driven by AMPA/kainate receptor-mediated transmission from mossy fiber afferents to the cerebellar nuclei. So, although plasticity in the cerebellar nuclei is not ruled out, it is unlikely that a long-term change in AMPA receptor-mediated transmission from mossy fiber inputs to the nuclei is an essential mechanism in eyeblink conditioning. Our findings indicate that a fully functional olivo-cortico-nuclear loop is required to express all characteristics of associatively conditioned responses.