A transient feature of the inferior olive supports thedevelopment of cerebellar internal models

Abstract

The inferior olive (IO) supports motor learning by supplying the cerebellum with critical sensory and motor input. In adult rats, that input includes externally generated limb stimulation. In contrast, the IO of postnatal day 8 (P8) rats does not exhibit responses to external stimuli. Instead, IO activity primarily reflects corollary discharges associated with the production of self-generated limb twitches during active (REM) sleep. Because corollary discharges are necessary for the computation of internal models, we tested the hypothesis that IO-related corollary discharge is necessary for the emergence of a functioning cerebellar internal model during development. First, by conducting extracellular recordings in the IO at P12 and P20, we confirmed the presence of twitch-related corollary discharge at both ages; however, whereas the IO at P20 responded to limb stimulation, the IO at P12 did not. Next, using a protocol for selectively lesioning the climbing fibers that connect the IO to the cerebellum, including the interpositus nucleus (IP), we confirmed that lesioning at P12 prevents the IPs expression of corollary discharge at P13. Finally, we assessed the necessity of IO input to the cerebellum for the emergence of an internal model by lesioning climbing fibers at P12 or P19 and testing for the expression of a cerebellar internal model in the thalamus at P20. Only when the lesions occurred at P12 was the expression of the internal model severely disrupted. These findings provide the most direct evidence to date linking twitch-related corollary discharge to the developmental emergence of a cerebellar-dependent internal model. SIGNIFICANCE STATEMENTIn adult animals, internal models of movement generated by the cerebellum are essential for smooth, precise, and adaptive behavior. It is known that these internal models must develop in early infancy in an experience-dependent fashion; however, it is not known how sensorimotor experience acting on the nascent cerebellar circuit gives rise to adult functions. Here, in pre-weanling rats, we show that self-generated signals during sleep provide the early experiences that shape cerebellar internal models. Our findings lay a foundation for understanding how neural activity during sleep shapes typical and atypical brain development.