A Novel FN-MdV Pathway and Its Role in Cerebellar Multimodular Control of Sensorimotor Behavior

Abstract

The cerebellum is crucial for various associative sensorimotor behaviors. Delay eyeblink conditioning (DEC) depends on the simplex lobule-interposed nucleus (IN) pathway, yet it is unclear how other cerebellar modules cooperate during this task. Here, we demonstrate the contribution of the vermis-fastigial nucleus (FN) pathway in controlling DEC. We found that task-related modulations in vermal Purkinje cells and FN neurons predict conditioned responses (CRs). Coactivation of the FN and the IN allows for the generation of proper motor commands for CRs, but only FN output fine-tunes unconditioned responses. The vermis-FN pathway launches its signal via the contralateral ventral medullary reticular nucleus, which converges with the command from the simplex-IN pathway onto facial motor neurons. We propose that the IN pathway specifically drives CRs whereas the FN pathway modulates the amplitudes of eyelid closure during DEC. Thus, associative sensorimotor task optimization requires synergistic modulation of different olivocerebellar modules that provide unique contributions.

Purkinje Cell Activity in Medial and Lateral Cerebellum During Suppression of Voluntary Eye Movements in Rhesus Macaques

“…The data on suppression PCs in the medial cerebellum showing a relatively late SS modulation during execution of both pro-and antisaccades as well as those on facilitation PCs in the lateral cerebellum showing a prominent modulation at the end of the instruction of antisaccades indicate that different modules of different cerebellar regions can simultaneously contribute to the same complex behavior, yet with different particularities. A similar conclusion was drawn from a recent study on delay eyeblink conditioning 70 . Even though this form of conditioning is classically considered to be controlled solely by modules in lobule simplex of the lateral cerebellum[Citation error], Wang and colleagues have shown that modules of the medial cerebellum are equally essential, yet also contributing in a slightly differential fashion, possibly regulating mainly muscle tone 70 .…”

“…A similar conclusion was drawn from a recent study on delay eyeblink conditioning 70 . Even though this form of conditioning is classically considered to be controlled solely by modules in lobule simplex of the lateral cerebellum[Citation error], Wang and colleagues have shown that modules of the medial cerebellum are equally essential, yet also contributing in a slightly differential fashion, possibly regulating mainly muscle tone 70 . Interestingly, similar to the current pro-and antisaccade tasks, during eyeblink conditioning the medial and lateral cerebellum also both engage facilitation and suppression cells, and they also operate at relatively low and high baseline firing frequencies, respectively 37,70 .…”

“…Even though this form of conditioning is classically considered to be controlled solely by modules in lobule simplex of the lateral cerebellum[Citation error], Wang and colleagues have shown that modules of the medial cerebellum are equally essential, yet also contributing in a slightly differential fashion, possibly regulating mainly muscle tone 70 . Interestingly, similar to the current pro-and antisaccade tasks, during eyeblink conditioning the medial and lateral cerebellum also both engage facilitation and suppression cells, and they also operate at relatively low and high baseline firing frequencies, respectively 37,70 . Our current finding that facilitation and suppression cells appear to play a more dominant role during the instruction and execution of the saccade task, respectively, further highlights the differential functional relevance of the upbound and downbound modules[Citation error].…”

Whisker kinematics in the cerebellum

“…For example, PC activity in the lobule simplex of rhesus monkeys correlates strongly with the velocity of horizontal eye movements (Marple-Horvat & Stein, 1990). Likewise, PCs in the lobule simplex of mice play a role in delay eyeblink conditioning (Heiney, Wohl et al, 2014;ten Brinke et al, 2015;Wang et al, 2020), while those in rabbits have been shown to contribute to conditioning of the nictitating membrane response (Schreurs et al, 1991). The current findings on a potential role of PCs in the murine lobule simplex in controlling kinematics of whisker movements are in line with the observations by Sharp & Gonzalez (1985), who showed that stimulation of the whiskers in rats alters activity in the lobule simplex.…”