Scientific Understanding of Consciousness
Consciousness as an Emergent Property of Thalamocortical Activity

Reward Expectation Encoded in Cerebellar Granule Cells


Nature  544, 96–100 (06 April 2017)

Cerebellar granule cells encode the expectation of reward

Mark J. Wagner,

Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA

Department of Electrical Engineering, Stanford University, Stanford, California 94305, USA

Department of Applied Physics, Stanford University, Stanford, California 94305, USA


The human brain contains approximately 60 billion cerebellar granule cells, which outnumber all other brain neurons combined. Classical theories posit that a large, diverse population of granule cells allows for highly detailed representations of sensorimotor context, enabling downstream Purkinje cells to sense fine contextual changes. Although evidence suggests a role for the cerebellum in cognition, granule cells are known to encode only sensory and motor context. Here, using two-photon calcium imaging in behaving mice, we show that granule cells convey information about the expectation of reward.

Mice initiated voluntary forelimb movements for delayed sugar-water reward. Some granule cells responded preferentially to reward or reward omission, whereas others selectively encoded reward anticipation. Reward responses were not restricted to forelimb movement, as a Pavlovian task evoked similar responses. Compared to predictable rewards, unexpected rewards elicited markedly different granule cell activity despite identical stimuli and licking responses. In both tasks, reward signals were widespread    throughout multiple cerebellar lobules. Tracking the same granule cells over several days of learning revealed that cells with reward-anticipating responses emerged from those that responded at the start of learning to reward delivery, whereas reward-omission responses grew stronger as learning progressed. The discovery of predictive, non-sensorimotor encoding in granule cells is a major departure from the current understanding of these neurons and markedly enriches the contextual information available to postsynaptic Purkinje cells, with important implications for cognitive processing in the cerebellum.

To our knowledge, this is the first in vivo recording of cerebellar granule cells during the execution and learning of goal-directed behaviour. Besides movement-encoding granule cells as predicted from previous studies, we found that granule cells signal reward expectation in multiple contexts and in all cerebellar lobules imaged. Reward-omission cells substantially outnumbered reward cells, even though reward is a sensory stimulus that elicits a greater licking response. This discrepancy may be related to our finding that omitted-reward responses increase while reward responses decrease during learning. The abundance of reward-omission granule cells could relate to cerebellar signalling of unexpected events.

Reward signals have been best studied in the ventral tegmental area (VTA) but also documented in other brain regions such as the ventral striatum, orbitofrontal cortex, and dorsal raphe nucleus. Most VTA dopamine neurons respond selectively to unexpected rewards or reward-predicting stimuli and are suppressed by omitted rewards. Thus, reward-anticipation granule cells do not resemble VTA responses. Rather, they are reminiscent of responses in striatum, orbitofrontal cortex, and dorsal raphe nucleus during goal-directed behaviour. Reward-omission signals are found mainly in anterior cingulate cortex and the lateral habenula. Granule cell reward signals could thus arise from many places, although originating from a direct VTA to cerebellum projection is unlikely. Neocortex provides an especially large mossy fibre input via the pons and thus merits further study.

An outstanding question is how reward context contributes to cerebellar function. Classical models posit that granule cells signal sensorimotor context. The incorporation of reward, reward-omission and reward-anticipation signals should allow the cerebellar cortex to integrate sensorimotor information with signals reflecting internal brain state, drive and affective status, and in so doing substantially expanding its function as a learning machine. Studying the causal role of these cells will require future technical advances to specifically manipulate reward-related granule cells without disrupting those essential for sensorimotor functions. Nevertheless, that granule cells can encode reward expectation clearly indicates that the contextual information available to downstream Purkinje cells is far richer than previously described, and provides a means for cerebellar involvement in a wide variety of cognitive computations.

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