Neuroscience
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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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Heterogeneity of Purkinje cells (PCs) that are arranged into discrete longitudinally-striped compartments in the cerebellar cortex is related to the timing of PC generation. To understand the cerebellar compartmental organization, we mapped the PC birthdate (or differentiation timing) in the entire cerebellar cortex. We used the birthdate-tagging system of Neurog2-CreER (G2A) mice hybridized with the AldocV strain which visualizes the zebrin (aldolase C) longitudinal striped pattern. ⋯ In the hemisphere, PCs of early and late birthdates were intermingled in the majority of areas. The results indicate that the birthdate of a PC is a partial determinant for the zebrin compartment in which it is located. However, the correlation between the PC birthdate and the zebrin compartmentalization is complex and distinct among the vermis, paravermis, hemisphere, nodulus, and flocculus.
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Review
Losing the beat: contribution of Purkinje cell firing dysfunction to disease, and its reversal.
The cerebellum is a brain structure that is highly interconnected with other brain regions. There are many contributing factors to cerebellar-related brain disease, such as altered afferent input, local connectivity, and/or cerebellar output. Purkinje cells (PC) are the principle cells of the cerebellar cortex, and fire intrinsically; that is, they fire spontaneous action potentials at high frequencies. ⋯ Notably, there are several cases where interventions that restore or rescue PC intrinsic activity also improve impaired behavior in these mouse models of disease. These findings suggest that rescuing PC firing deficits themselves may be sufficient to improve impairment in cerebellar-related behavior in disease. We propose that restoring PC intrinsic firing represents a good target for drug development that might be of therapeutic use for several disorders.