Multiple signals evoked by unisensory stimulation converge onto cerebellar granule and Purkinje cells in mice

Abstract

The cerebellum receives signals directly from peripheral sensory systems and indirectly from the neocortex. Even a single tactile stimulus can activate both of these pathways. Here we report how these different types of signals are integrated in the cerebellar cortex. We used in vivo whole-cell recordings from granule cells and unit recordings from Purkinje cells in mice in which primary somatosensory cortex (S1) could be optogenetically inhibited. Tactile stimulation of the upper lip produced two-phase granule cell responses (with latencies of 8 ms and 29 ms), for which only the late phase was S1 dependent. In Purkinje cells, complex spikes and the late phase of simple spikes were S1 dependent. These results indicate that individual granule cells combine convergent inputs from the periphery and neocortex and send their outputs to Purkinje cells, which then integrate those signals with climbing fiber signals from the neocortex.

Altered Cerebellar Response to Somatosensory Stimuli in theCntnap2Mouse Model of Autism

“…shown by this model in the eye-blink conditioning test, another paradigm widely used to study cerebellar function (Kloth et al, 2015). The appearance of the stimulus-evoked CS has been shown to be modulated by activity from the somatosensory cortex, since the suppression of S1 activity abolishes CS appearance upon tactile stimulation (Shimuta et al, 2020). Further, diminishing S1 activity lengthens and enhancing it shortens CS appearance latency (Brown and Bower, 2002).…”

Altered cerebellar response to somatosensory stimuli in the Cntnap2 mouse model of autism

“…In agreement with this, dysfunction of the olivocerebellar circuit in Cntnap2 mice was proposed as responsible for the decreased response probability shown by this model in the eye-blink conditioning test, another paradigm widely used to study cerebellar function (Kloth et al, 2015). The appearance of the stimulus-evoked CS has been shown to be modulated by activity from the somatosensory cortex, since the suppression of S1 activity abolishes CS appearance upon tactile stimulation (Shimuta, Sugihara, & Ishikawa, 2020). Further, diminishing S1 activity lengthens and enhancing it shortens CS appearance latency (Brown & Bower, 2002).…”

Purkinje Cell Activity Determines the Timing of Sensory-Evoked Motor Initiation

“…These considerations can explain why there was no significant distinction in coherent complex spike signals between multisensory and unisensory stimuli ( Figures S6 A–S6F): both are perceived as sensory stimuli requiring lick initiation or strongly predicting the future reward. Therefore, multisensory integration could take place in brain regions upstream of the cerebellum, such as sensory and association cortex, which project to the inferior olivary neurons, providing climbing fiber inputs to Crus I ( Shimuta et al., 2020 ). Simultaneous recordings from these brain regions and the cerebellum ( Wagner et al., 2019 ) could address this possibility.…”