The Neuronal Code(s) of the Cerebellum

Abstract

Understanding how neurons encode information in sequences of action potentials is of fundamental importance to neuroscience. The cerebellum is widely recognized for its involvement in the coordination of movements, which requires muscle activation patterns to be controlled with millisecond precision. Understanding how cerebellar neurons accomplish such high temporal precision is critical to understanding cerebellar function. Inhibitory Purkinje cells, the only output neurons of the cerebellar cortex, and their postsynaptic target neurons in the cerebellar nuclei, fire action potentials at high, sustained frequencies, suggesting spike rate modulation as a possible code. Yet, millisecond precise spatiotemporal spike activity patterns in Purkinje cells and inferior olivary neurons have also been observed. These results and ongoing studies suggest that the neuronal code used by cerebellar neurons may span a wide time scale from millisecond precision to slow rate modulations, likely depending on the behavioral context. IntroductionThe cerebellum has long been regarded as a purely sensorimotorrelated structure, crucial for the precise temporal coordination of body, limb, and eye movements and the learning and fine-tuning of motor skills. Electrophysiological investigations of the cerebellar cortical principal neurons, the Purkinje cells, and their postsynaptic targets, the neurons in the cerebellar nuclei (CN) and vestibular nuclei, revealed strong representations of a wide variety of sensory and motor events (Ito, 1984; Strata, 1989) in the presence of high sustained spike rates (Thach, 1972).Extracellular single-unit recordings, particularly those conducted in awake and behaving nonhuman primates, have established that Purkinje cell simple spike rates represent a variety of variables related to the control of eye, head, and limb movements. Encoded variables include the direction of limb movements (e.g., Harvey et al., 1977; Thach, 1978; Fortier et al., 1989; Smith et al., 1993) and limb movement velocity or speed (Coltz et al., 1999; Roitman et al., 2005). Studies of arm movement dynamics provided evidence that Purkinje cell simple spike activity represents both forward prediction and feedback error-related signals, consistent with an involvement of the cerebellum in the prediction of expected sensorimotor states and the detection and correction of motor errors ; for a recent review, see Ebner et

Motor Learning and the Cerebellum

“…There must be obvious benefits preserved throughout evolution (Darwin 1859). Clearly, control of motor learning is one of the prime functions of the cerebellum (Ito 2002;De Zeeuw et al 2011;Gao et al 2012) and exploiting diversity in intrinsic activity of its main output neurons like Purkinje cells and cerebellar nuclei neurons may benefit the execution of this function, but other regions like the cerebral cortex also have prime roles in learning, including both declarative and procedural memory formation, whereas their main output neurons, pyramidal cells, usually fire at a relatively low firing frequency at rest, preserving energy (Heck et al 2013;Pouille et al 2013).…”

“…n the formation of procedural memories, the cerebellum shows at least two types of information coding within its massive neuronal networks (De Zeeuw et al 2011;Person and Raman 2012;Heck et al 2013;Yang and Lisberger 2013). Modulation of the average firing rate of neuronal spikes or "rate coding" is most often proposed as the predominant mechanism of information coding used for motor learning (Boyden et al 2004;Lisberger 2009;Walter and Khodakhah 2009).…”

Relative contribution of TARPs γ-2 and γ-7 to cerebellar excitatory synaptic transmission and motor behavior

“…1), indicating a critical role for γ-7 in PCs. Cerebellar PCs are the sole output neurons of the cerebellar cortex and project to the deep cerebellar nuclei and vestibular nuclei neurons, which are involved in motor control in animals through their communication with the nuclei of the thalamus and brainstem (27). In stg mutant mice, γ-2 gene expression is disrupted at the genomic level and excitatory transmission is affected to varying degrees at all excitatory synapses in the cerebellum (and anywhere in brain where γ-2 is expressed), presumably accounting for the ataxic phenotype.…”

The Mechanisms and Functions of Synaptic Facilitation

“…A similar role for facilitation was observed in mice at cerebellar output synapses between Purkinje cells and the deep cerebellar nuclei (Turecek et al, 2016). Purkinje cells typically fire action potentials continuously at high rates in vivo , and can encode information by modulating their firing rates (Heck et al, 2013). At many synapses depletion is more prominent at high frequencies, and steady-state transmission decreases with firing frequency.…”