Neuroscience
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The geometry of the glutamatergic mossy-parallel fibre and climbing fibre inputs to cerebellar cortical Purkinje cells has powerfully influenced thinking about cerebellar functions. The compartmentation of the cerebellum into parasagittal zones, identifiable in olivo-cortico-nuclear projections, and the trajectories of the parallel fibres, transverse to these zones and following the long axes of the cortical folia, are particularly important. Two monoaminergic afferent systems, the serotonergic and noradrenergic, are major inputs to the cerebellar cortex but their architecture and relationship with the cortical geometry are poorly understood. ⋯ An individual serotonergic fibre must influence all zones and microzones within its medial-lateral trajectory. In contrast, noradrenergic fibres can influence smaller cortical territories, potentially as limited as a microzone. Evidence is emerging that these monoaminergic systems may not supply a global signal to all of their targets and their potential for cerebellar cortical functions is discussed.
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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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Retinoid-related orphan receptor α (RORα) is a transcription factor expressed in a variety of tissues throughout the body. Knockout of RORα leads to various impairments, including defects in cerebellar development, circadian rhythm, lipid metabolism, immune function, and bone development. Previous studies have shown significant reduction of RORα expression in Purkinje cells (PCs) of spinocerebellar ataxia (SCA) type 1 and type 3/MJD (Machado-Joseph disease) model mice. ⋯ In behavioral experiments, mice expressing miR-RORα showed motor learning deficits, and later, overt cerebellar ataxia. Thus, RORα in mature PCs plays pivotal roles in maintenance of PC dendrites and the monolayer alignment, and consequently, motor learning and motor function. Decrease in RORα expression in PCs could be a primary etiology of the cerebellar symptoms in patients with SCA1 and SCA3/MJD.
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In 2017, the Food and Drug Administration published a safety recommendation to limit the exposure to general anesthesia as much as possible below the age of three. Indeed, several preclinical and clinical studies have questioned the possible toxicity of general anesthesia on the developing brain. Since then, recent clinical studies tried to mitigate this alarming issue. ⋯ Only stronger translational research will allow scientists to provide concrete answers to this public health issue. In this review, we will provide and discuss the more recent data in this field, including the point of view of preclinical researchers, neuropsychologists and pediatric anesthesiologists. Through translational research, preclinical researchers have more than ever a role to play to better understand and identify long-term effects of general anesthesia for pediatric surgery on brain development in order to minimize it.