Developmentally unique cerebellar processing prioritizes self- over other-generated movements

Abstract

AbstractTo compute internal models of movement, the cerebellum must distinguish sensory input arising from self- and other-generated movements (reafference and exafference, respectively). This distinction is enabled by copies of motor commands (i.e., corollary discharges) that are sent to the cerebellum. The capacity to compute internal models emerges gradually through a process that is not yet understood. Previously, we demonstrated in 8-day-old (P8) rats that precerebellar nuclei—including the inferior olive and lateral reticular nucleus—convey corollary discharge and reafference to the cerebellum during active (REM) sleep when pups produce self-generated limb twitches. By P20, the cerebellum is able to compute an internal model and convey it to motor thalamus via the interpositus nucleus (IP). Here, recording from IP in P12 rats, we compare reafferent and exafferent responses to twitches and limb stimulations, respectively. As expected, most IP units show robust and reliable responses to twitches. However, in contrast with other sensory structures throughout the brain, exafferent responses in IP are neither robust nor reliable. Upon finding that exafferent responses occur in pups under urethane anesthesia, we hypothesized that urethane inhibits cerebellar cortical cells, thereby disinhibiting exafferent responses in IP. In support of this hypothesis, ablating cortical tissue dorsal to IP mimics the effects of urethane on exafference. Finally, twitch-related corollary discharge and reafference are conveyed to IP and cerebellar cortex in parallel. Based on these results, we propose that twitches provide opportunities for the nascent cerebellum to integrate somatotopically organized input, thereby enabling the development of closed-loop circuits and, subsequently, internal models.SignificanceStatementFor adult animals to produce flexible and adaptive movements, they must distinguish self- from other-generated movements and learn to anticipate how their body moves through space. The computations required for this capacity occur within the cerebellar system. In early infancy, these computations are not yet established and must develop through sensorimotor experience. By comparing how the infant cerebellum processes sensory input, we found that it prioritizes input associated with self-generated movements. Such prioritization appears unique to the infant cerebellum and helps us understand how that structure establishes its adult neural circuity and functions.