Electrophysiological localization of eyeblink-related microzones in rabbit cerebellar cortex.
The classically conditioned eyeblink response in the rabbit is one of the best-characterized behavioral models of associative learning. It is cerebellum dependent, with many studies indicating that the hemispheral part of Larsell's cerebellar cortical lobule VI (HVI) is critical for the acquisition and performance of learned responses. However, there remain uncertainties about the distribution of the critical regions within and around HVI. In this learning, the unconditional stimulus is thought to be carried by periocular-activated climbing fibers. Here, we have used a microelectrode array to perform systematic, high-resolution, electrophysiological mapping of lobule HVI and surrounding folia in rabbits, to identify regions with periocular-evoked climbing fiber activity. Climbing fiber local field potentials and single-unit action potentials were recorded, and electrode locations were reconstructed from histological examination of brain sections. Much of the sampled cerebellar cortex, including large parts of lobule HVI, was unresponsive to periocular input. However, short-latency ipsilateral periocular-evoked climbing fiber responses were reliably found within a region in the ventral part of the medial wall of lobule HVI, extending to the base of the primary fissure. Small infusions of the AMPA/kainate receptor antagonist CNQX into this electrophysiologically defined region in awake rabbits diminished or abolished conditioned responses. The known parasagittal zonation of the cerebellum, supported by zebrin immunohistochemistry, indicates that these areas have connections consistent with an essential role in eyeblink conditioning. These small eyeblink-related areas provide cerebellar cortical targets for analysis of eyeblink conditioning at a neuronal level but need to be localized with electrophysiological identification in individual animals.
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