Movement Rate Is Encoded and Influenced by Widespread, Coherent Activity of Cerebellar Molecular Layer Interneurons

Abstract

Inhibition from molecular layer interneurons (MLIs) is thought to play an important role in cerebellar function by sharpening the precision of Purkinje cell spike output. Yet the coding features of MLIs during behavior are poorly understood. To study MLI activity, we used in vivo Ca 2ϩ imaging in head-fixed mice during the performance of a rhythmic motor behavior, licking during water consumption. MLIs were robustly active during lick-related movement across a lobule-specific region of the cerebellum showing high temporal correspondence within their population. Average MLI Ca 2ϩ activity strongly correlated with movement rate but not to the intentional, or unexpected, adjustment of lick position or to sensory feedback that varied with task condition. Chemogenetic suppression of MLI output reduced lick rate and altered tongue movements, indicating that activity of these interneurons not only encodes temporal aspects of movement kinematics but also influences motor outcome pointing to an integral role in online control of rhythmic behavior.

How a mouse licks a spout: Cortex-dependent corrections as the tongue reaches for, and misses, targets

“…Cues evoked bouts of licking, as previously observed in head-fixed mouse setups where the spout could not be directly seen (Fig. 1B, Inter spout contact interval: 150ms±11ms, Inter lick interval:142±5ms, n = 9 animals) (8,11). We defined 'cue-evoked licks' as licks initiated before first spout contact and 'water-retrieval licks' as licks initiated after the first tongue-spout contact in a bout (14) (Fig 1A, G-H).…”

“…tractable model systems such as rodents where licking is used to study principles of motor initiation, learning, planning, and decision making (8)(9)(10)(11)(12)(13)(14), licks are usually measured as a binary register of whether or not a tongue contacts a spout or transects an IR beam (8,9) or with single plane imaging (10,11). Remarkably, it remains unclear how exactly the tongue moves during rodent licking.…”

Conversion of graded presynaptic climbing fiber activity into graded postsynaptic Ca2+ signals by Purkinje cell dendrites

“…CF responses in Crus I were not due to motor action as sensory-related activity persisted under anesthesia-induced paralysis. In previous studies, we also observed lobule-specific differences in the representation of behavioral variables, with orofacial movements in response to reward consumption engaging neurons in Crus II but not Crus I (Gaffield et al, 2016;Gaffield and Christie, 2017). Combined, these results suggest partitioned representations of unpredicted sensations and mechanics of action within the lateral posterior hemispheres, cerebellar regions increasingly implicated in cognitive function in both humans and mice (Deverett et al, 2018;Schmahmann, 2018;Stoodley et al, 2017).…”

“…Interestingly, there was evidence of partitioned processing of sensation and action within distinct regions of the lateral cerebellum. In lobule Crus II, where PCs are responsive to motorrelated CF activity (Gaffield et al, 2016;Gaffield and Christie, 2017), sensory cues failed to alter the rate of dendritic Ca 2+ events compared to baseline (1.22 ± 0.12 and 1.20 ± 0.14 Hz; prior to and during sensory stimuli, respectively; n = 39 trial blocks, 6 mice; p = 0.93; paired Student's t-test; Figure 1C). Given that sensory-triggered Ca 2+ events persisted in PCs of Crus I while animals were under anesthesia-induced paralysis, we rule out movement as the direct cause of CF responses in this region (Figure 1F).…”

Morphological pseudotime ordering and fate mapping reveals diversification of cerebellar inhibitory interneurons

“…Canonical BCs and SCs were identified according to standards in literature (Amat et al 2017;Sergaki et al 2017;Gaffield and Christie 2017;Sultan and Bower 1998). Canonical BCs were identified by: 1) soma location within the bottom ⅓ of the ML, 2) a long horizontal axonal shaft which gives rise to basket terminals, and 3) a dendritic arbor which reaches the apical ML.…”