Shared Cortex-Cerebellum Dynamics in the Execution and Learning of a Motor Task

Abstract

Graphical Abstract Highlights d First simultaneous recordings from neocortex and cerebellum over weeks of learning d Cortical layer 5 and cerebellar granule cells show similar task encoding in experts d Learning increases correlations among initially dissimilar L5 and granule cells d L5 and granule cells converge to similar, low-dimensional, task-encoding activity Correspondence mjwagner@stanford.edu (M.J.W.), mschnitz@stanford.edu (M.J.S.), lluo@stanford.edu (L.L.) In BriefSimultaneous recordings of ensembles of individual neurons in the neocortex and cerebellum provide a view of how these two brain regions learn together. SUMMARYThroughout mammalian neocortex, layer 5 pyramidal (L5) cells project via the pons to a vast number of cerebellar granule cells (GrCs), forming a fundamental pathway. Yet, it is unknown how neuronal dynamics are transformed through the L5/GrC pathway. Here, by directly comparing premotor L5 and GrC activity during a forelimb movement task using dual-site two-photon Ca 2+ imaging, we found that in expert mice, L5 and GrC dynamics were highly similar. L5 cells and GrCs shared a common set of task-encoding activity patterns, possessed similar diversity of responses, and exhibited high correlations comparable to local correlations among L5 cells. Chronic imaging revealed that these dynamics co-emerged in cortex and cerebellum over learning: as behavioral performance improved, initially dissimilar L5 cells and GrCs converged onto a shared, lowdimensional, task-encoding set of neural activity patterns. Thus, a key function of cortico-cerebellar communication is the propagation of shared dynamics that emerge during learning.(A) Experimental schematics. Mice voluntarily moved a manipulandum for sucrose water reward (left). We performed simultaneous Ca 2+ imaging in cerebellar GrCs through a cranial window, and in L5 pyramidal neurons of the premotor cortex using an implanted 1 mm prism (right). GCaMP6f was expressed in L5 cells and GrCs using quadruple transgenic mice Rbp4-Cre/Math1-Cre/Ai93/ztTA. (B) Mean images from representative two-photon Ca 2+ imaging movies in L5 cells (left) and GrCs (right). The spatial filters used to extract fluorescence traces from cells with detected activity are highlighted in grayscale or red/blue (see G below; n = 144 L5 cells/177 GrCs). (C) Forelimb movement task. Water-restricted mice self-initiated trials. The task alternated blocks of 40 trials in which forward movement was followed by a left turn with blocks of 40 trials in which forward movement was followed by a right turn. No cues indicated trial type. (D) Example movements on the virtual right-angle track (left, n = 20 each of pure left and right turns; right, n = 8 error-correction turns in each direction). (E) Average motion over time in forward (black curve) and lateral (colored curves) directions for all pure turn trials in the session in (D), aligned temporally to turn onset (n = 51/63 pure-left/pure-right turns). Dashed vertical line denotes average forward movement onset. (F) Behavioral performanc...

NINscope: a versatile miniscope for multi-region circuit investigations

“…Leveraging the capabilities of our miniscope, we demonstrate functional interactions between the cerebellum and cortex in unrestrained mice wearing dual miniscopes. Complex spike activity in Purkinje cell dendrites correlated with cellular activity measured in the cortex during periods of movement, in line with previous anatomical and functional studies of cerebello-thalamo-cortical connectivity (Badura et al 2018;Bostan, Dum, and Strick 2013;Akkal, Dum, and Strick 2007;Hoover and Strick 1999;Gao et al 2018;Wagner et al 2019) . Moreover, activity correlated across regions typically preceded behavioral acceleration.…”

Differential encoding in prefrontal cortex projection neuron classes across cognitive tasks

“…Choice-specific information has been observed across multiple regions of cortex (Feierstein et al, 2006;Harvey et al, 2012;Guo et al, 2014b;Li et al, 2015;Driscoll et al, 2017;Wagner et al, 2019). Similarly, we found that many vmPFC cells exhibited activity selective not only for the task epoch, but also for left or right choice directions ( Figures 6A, S6D).…”

Motor learning and transfer: from feedback to feedforward control

“…Primary motor cortex activity is also modified during motor learning in the context of self-initiated reaching (Sanes and Donoghue, 2000;Li et al, 2001;Diedrichsen et al, 2005;Kawai et al, 2015) , though, to our knowledge, no studies have definitively linked primary motor cortex to the learning process itself. Another likely common node, especially for the learning process, is the cerebellum, which is richly interconnected with primary motor cortex (Wagner et al, 2019) . Cerebellar circuits are strongly implicated in multi-joint coordination during both feedforward control and feedback responses (Holmes, 1939;Goodkin et al, 1993;Bastian et al, 1996Bastian et al, , 2000Kurtzer et al, 2013;Wagner et al, 2019) and have long been hypothesized to house the computations related to internal models (Wolpert et al, 1998;Kawato, 1999) .…”

“…Another likely common node, especially for the learning process, is the cerebellum, which is richly interconnected with primary motor cortex (Wagner et al, 2019) . Cerebellar circuits are strongly implicated in multi-joint coordination during both feedforward control and feedback responses (Holmes, 1939;Goodkin et al, 1993;Bastian et al, 1996Bastian et al, , 2000Kurtzer et al, 2013;Wagner et al, 2019) and have long been hypothesized to house the computations related to internal models (Wolpert et al, 1998;Kawato, 1999) .…”