Post published on Twitter/X on 25 Dec 2021 03:59

Abstract

Summary Perturbation to the cerebellum can lead to deficits in motor function, cognition, and behavioral flexibility. Here we report that a cerebellum-specific transgenic mouse autism model with disrupted Purkinje cell function shows unexpectedly accelerated learning on a sensory evidence-accumulation task, as well as enhanced sensory reactivity to touch and auditory cues. Computational latent-state analysis of behavior revealed that accelerated learning was associated with enhanced focus on current over past trials. In on-task states, a subset of Purkinje cells in crus I produced more complex spikes to sensory stimuli. Learning was accelerated by providing cue-locked optogenetic stimulation of Purkinje cells, but unaffected by continuous optogenetic interference with Purkinje cell activity. Complex spikes fired in response to both correct and incorrect choices, but less so when mice were on-task. Both transgenic mice and mice receiving cue-locked optogenetic stimulation showed prolonged sensory responses in Purkinje-cell complex spikes and anterior cingulate cortex. We suggest that cerebellar activity may shape evidence-accumulation learning by enhancing task focus and neocortical processing of current experience. Highlights Faster learning and enhanced sensory salience with cerebellar manipulations in mice Accelerated learning arises from prolonged occupancy in an on-task behavioral state Cerebellar manipulations can influence neocortex via altered complex spike activity Cerebellum findings consistent with a weak global coherence account of autism eTOC blurb In a cerebellum-based mouse autism model, perturbed function leads to faster learning of a working-memory task, mediated by higher focus on current trials. The effects are emulated by optogenetic perturbation of Purkinje cells, and both perturbations drive enhanced neocortical activity. Results are consistent with a weak coherence model for autism.