Locomotor activity modulates associative learning in mouse cerebellum

Abstract

Changes in behavioral state are associated with modulation of sensory responses across visual, auditory and somatosensory cortices. Here we show that locomotor activity independently modulates performance in delay eyeblink conditioning, a cerebellumdependent form of associative learning. Increased locomotor speed in head-fixed mice was associated with earlier onset of learning and trial-by-trial enhancement of learned responses. The influence of locomotion on conditioned responses was dissociable from changes in arousal and was independent of the sensory modality of the conditioned stimulus. Eyelid responses evoked by optogenetic stimulation of mossy fiber terminals within the cerebellar cortex, but not at sites downstream, were also positively modulated by ongoing locomotion. We conclude that locomotor activity modulates delay eyeblink conditioning through mechanisms acting on the mossy fiber pathway within the cerebellar cortex. Taken together, these results suggest a novel role for behavioral state modulation in associative learning and provide a potential mechanism through which engaging in movement can improve an individual's ability to learn.

Motor context dominates output from Purkinje cell functional regions during reflexive visuomotor behaviours

“…These results suggest that motor efference signals during whole-body locomotion (swimming) drive 1090 simple spike output in nearly all cerebellar Purkinje cells in the larval zebrafish. Our current granule cell population imaging and electrophysiological recordings in zebrafish together with other recordings and optogenetic experiments in zebrafish and mice (Ozden et al, 2012;Powell et al, 2015;Jelitai et al, 2016;Giovannucci et al, 2017;Knogler et al, 2017;Albergaria et al 2018) provide strong evidence that the cerebellum broadly encodes intended locomotor output or signals 1095 related to it in the input layer ( Figure 6). These findings suggest an enrichment of motor signals across parallel fiber inputs, though some regional specialization of signals in limbed vertebrates may be needed to coordinate different limb networks.…”

NMDAR-dependent emergence of behavioral representation in primary visual cortex

“…Several groups have shown that classical eyeblink conditioning provides an excellent model for investigating the neural correlates of sensorimotor learning [26][27][28][29] . We recently showed that mice rapidly learn to form associations between visual stimuli and aversive corneal air-puffs, resulting in expression of a conditioned blink response 21 .…”

Cerebellum-specific deletion of the GABAAreceptor δ subunit alters anxiety-like, social and maternal behaviors without affecting motor performance

“…A conditioning stimulus (CS, a weak illumination) that does not initially cause the eye to close, is paired with an unconditioned stimulus (US, air puff to the eye) that causes the eye to close. Delay conditioning experiments were performed in mice running on a rotating platform as the CS and US were presented (Albergaria et al, 2018). The CS occurs for 500 ms, and for the last 50 ms it is paired with the US.…”