Neuroscience
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As a tribute to Masao Ito, we propose a model of cerebellar learning that incorporates and extends his original model. We suggest four principles that align well with conclusions from multiple cerebellar learning systems. (1) Climbing fiber inputs to the cerebellum drive early, fast, poorly-retained learning in the parallel fiber to Purkinje cell synapse. (2) Learned Purkinje cell outputs drive late, slow, well-retained learning in non-Purkinje cell inputs to neurons in the cerebellar nucleus, transferring learning from the cortex to the nucleus. (3) Recurrent feedback from Purkinje cells to the inferior olive, through interneurons in the cerebellar nucleus, limits the magnitude of fast, early learning in the cerebellar cortex. (4) Functionally different inputs are subjected to plasticity in the cerebellar cortex versus the cerebellar nucleus. A computational neural circuit model that is based on these principles mimics a large amount of neural and behavioral data obtained from the smooth pursuit eye movements of monkeys.
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Autism spectrum disorders (ASD) are highly prevalent neurodevelopmental disorders; however, the neurobiological mechanisms underlying disordered behavior in ASD remain poorly understood. Notably, individuals with ASD have demonstrated difficulties generating implicitly derived behavioral predictions and adaptations. ⋯ In this review, we will utilize the foundational, theoretical contributions of the late neuroscientist Masao Ito to establish an internal model framework for the cerebellar contribution to ASD-relevant behavioral predictions and adaptations. Additionally, we will also explore and then apply his key experimental contributions towards an improved, mechanistic understanding of the contribution of cerebellar dysfunction to ASD.
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Abnormal tremors are the most common of all movement disorders. In this review we focus on the role of the cerebellum in Essential Tremor, a highly debilitating but poorly treated movement disorder. We propose a variety of mechanisms driving abnormal burst firing of deep cerebellar nuclei neurons as a key initiator of tremorgenesis in Essential Tremor. Targetting these mechanisms may generate more effective treatments for Essential Tremor.
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In the last 50 years, our vision of the cerebellum has vastly evolved starting with Voogd's (1967) description of extracerebellar projections' terminations and how the projection maps transformed the presumptive homogeneity of the cerebellar cortex into a more complex center subdivided into transverse and longitudinal distinct functional zones. The picture became still more complex with Richard Hawkes and colleagues' (Gravel et al., 1987) discovery of the biochemical heterogeneity of Purkinje cells (PCs), by screening their molecular identities with monoclonal antibodies. ⋯ The correlation of these two maps in adult cerebellum shows a perfect matching of developmental mechanisms. This review discusses a series of arguments in favor of the essential role played by PCs in organizing the microzonation of the cerebellum during development (the "matching" hypothesis).
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Purkinje cells (PCs) are principal cerebellar neurons, and several classes of interneurons modulate their activity. Lugaro cells (LCs) are one such inhibitory interneuron with distinctive cytology and location, but still most enigmatic among cerebellar neurons. Here we serendipitously produced a novel transgenic mouse line, where a half of Yellow Cameleon (YC)(+) cells in the cerebellar cortex were judged to be LCs, and YC(+) LCs were estimated to constitute one-third of the total LC populations. ⋯ In turn, YC(+) LCs projected a dense lattice of ascending and transverse axons to the molecular layer, and innervated molecular layer interneurons (basket and stellate cells) and Golgi cells, but not PCs. Of note, ascending axons profusely innervated individual targets within a cerebellar compartment, while transverse axons ran across several compartments and innervated targets sparsely. This unique circuit configuration highlights that LCs integrate various excitatory, inhibitory, and modulatory inputs coming to the belonging cerebellar compartment and that, as an interneuron-selective interneuron, LCs can effectively disinhibit cerebellar cortical activities in a compartment-dependent manner through inhibition of inhibitory interneurons selectively targeting PCs and granule cells.