Electrophysiological Localization of Eyeblink-Related Microzones in Rabbit Cerebellar Cortex

Abstract

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.

Precise Control of Movement Kinematics by Optogenetic Inhibition of Purkinje Cell Activity

“…Three of these climbing fibers were tested with both ipsilateral and contralateral puffs and all showed reliable responses only to ipsilateral puffs (Fig. 3C), which is consistent with previous work (Mostofi et al, 2010). Second, microstimulation with high electrical currents (Ͼ100 A) in the same location generated a characteristic "delayed blink," a pronounced eyelid closure that occurs with a fixed latency after terminating the stimulation regardless of stimulus duration (Hesslow, 1994; Fig.…”

“…The marking lesions in Figure 3A (black triangles) pinpoint an area of mouse cerebellar cortex that satisfied two criteria used in previous studies to define an eyeblink microzone in other animal species (Hesslow, 1994;Mostofi et al, 2010). First, PCs within this location received climbing fiber input that was time locked to a periocular puff stimulus, with median latencies of 22 ms (range ϭ 17.5-27 ms, n ϭ 7 neurons; Fig.…”

“…Histological examination of electrolytic lesions made in this location revealed that the mouse eyeblink microzone is at the floor of the primary fissure ϳ5.6 mm posterior from bregma (Fig. 3A), a location that is near eyeblink microzones previously identified in rabbit lobules V/HVI (Garcia et al, 1999;Mostofi et al, 2010).…”

“…The areas of cerebellar cortex that are involved in the control of eyelid movements are known in other animal species (Hesslow, 1994;Garcia et al, 1999;Mostofi et al, 2010), but not in mice. Therefore, we first performed a series of experiments to establish the location of a blink-related area in mouse cerebellar cortex.…”

Zebrin-Immunopositive and -Immunonegative Stripe Pairs Represent Functional Units in the Pigeon Vestibulocerebellum

“…Fewer studies have attempted to relate the sagittal ZII stripes to PC function (Gao et al, 2006;Mostofi et al, 2010). In this regard, our laboratory has been investigating the pigeon vestibulocerebellum (VbC) (folia IXcd and X) where complex spike activity (CSA) of PCs responds best to optic flow stimuli (Graf et al, 1988;Wylie and Frost, 1999).…”