Cerebellar contribution to preparatory activity in motor neocortex

Abstract

Lead contact: t.mrsic-flogel@ucl.ac.uk 7 8In motor neocortex, preparatory activity predictive of specific movements is maintained by a positive 9 feedback loop with the thalamus. Motor thalamus receives excitatory input from the cerebellum, 10 which learns to generate predictive signals for motor control. The contribution of this pathway to 11 neocortical preparatory signals remains poorly understood. Here we show that in a virtual reality 12 conditioning task, cerebellar output neurons in the dentate nucleus exhibit preparatory activity 13 similar to that in anterolateral motor cortex prior to reward acquisition. Silencing activity in dentate 14 nucleus by photoactivating inhibitory Purkinje cells in the cerebellar cortex caused robust, short-15 latency suppression of preparatory activity in anterolateral motor cortex. Our results suggest that 16 preparatory activity is controlled by a learned decrease of Purkinje cell firing in advance of reward 17 under supervision of climbing fibre inputs signalling reward delivery. Thus, cerebellar computations 18 exert a powerful influence on preparatory activity in motor neocortex. 19 20 21 to upcoming movements or salient events such as reward (Giovannucci et al., 2017;Huang et al., 2013; 48 Kennedy et al., 2014; Wagner et al., 2017). For instance, DN neurons exhibit ramping activity predictive 49 of the timing and direction of the self-initiated saccades (Ashmore and Sommer, 2013; Ohmae et al., 50 2017). Moreover, inactivation of IPN activity reduces persistent activity in a region of medial prefrontal 51 cortex involved in trace eyeblink conditioning (Siegel and Mauk, 2013). Finally, a recent study has 52 established the existence of a loop between ALM and the cerebellum necessary for the maintenance of 53 preparatory activity (Gao et al., 2018). These results suggest that the cerebellum participates in 54 programming future actions, but the details of how it may contribute to preparatory activity in the 55 neocortex during goal-directed behaviour remain to be determined. 56 57 RESULTS 58 59 Preparatory activity in ALM prior to reward acquisition in a virtual corridor 60We developed a visuomotor task in which mice ran through a virtual corridor comprising salient visual 61 cues to reach a defined location where a reward was delivered (80 cm from the appearance of the 62 second checkerboard pattern; Figure 1A; see Methods). Within a week of training, mice learned to 63 128The cerebellar dentate nucleus exhibits preparatory activity 129Since the DN sends excitatory projections to the motor thalamus (Guo et al., 2017;Ichinohe et al., 2000; 130 Middleton and Strick, 1997; Thach and Jones, 1979), which has been shown to participate in the 131 maintenance of preparatory activity in mouse ALM neocortex (Guo et al., 2017), we investigated 132 whether DN activity could influence ALM processing. We first recorded the activity of DN neurons to 133 determine how their activity was modulated during the task (Figure 2A). Forty four percent of all 134 recorded DN neurons (n =...

A functional cortical network for sensorimotor sequence generation

“…In addition, we found that τ exhibited properties of a reward expectation signal, and D and θ also showed reward-related modulations. This is consistent with recent work showing reward-related activity in ALM that depends on output from the cerebellar dentate nucleus 44 . These variables may contribute to other processes other than sequence execution, such as representing instantaneous action values for motor learning.…”

Cerebellar Purkinje cells can differentially modulate coherence between sensory and motor cortex depending on region and behavior

“…Moreover, these findings also suggest that the cerebellum may better control motor behavior by temporarily downgrading the coherence with sensory relevant signals rather than enhancing them. These implications agree with the high-frequency mode of simple spike activity and modulation that take place during the preparation and execution of motor coordination (Brown and Raman, 2018;Gao et al, 2018;Romano et al, 2018;Chabrol et al, 2019). Indeed, we found that the suppressive impact of Purkinje cell stimulation on gamma band oscillations was greater during larger input during self-motion (Urbain and Deschênes, 2007;Furuta et al, 2010;Bosman et al, 2011;Schäfer and Hoebeek, 2018), which highlights its role as an important intermediate between cerebellum and neocortex.…”

Attractor dynamics gate cortical information flow during decision-making

“…Our work also suggests a new computational role for the ramping signal, which has been observed in many decision-making tasks and is related to time estimation and a sense of urgency (69,70,7,5,71,72,14). Ramping might act as a temporal discounting signal for incoming sensory inputs by gradually increasing the commitment to the selected action (34), by moving attractors apart over time.…”