Neuroscience
-
Biological motions commonly contain multiple frequency components in which each fundamental has to be adjusted by motor learning to acquire a new motor skill or maintain acquired skills. At times during this motor performance one frequency component needs to be enhanced (gain-up) while another is suppressed (gain-down). This pattern of simultaneous gain-up and -down adjustments at different frequencies is called frequency competitive motor learning. ⋯ These results demonstrate that the cerebellum is required for all frequency competitive VOR motor learning and Purkinje cell activity therein is well correlated with all gain-down behaviors independent of frequency. However, frequency competitive gain-up learning requires intact, recursive brainstem/cerebellar pathways. Collectively these findings support the idea that VOR gain-up and gain-down learning utilize separate brainstem/cerebellar circuitry that, in turn, clearly underlies the unique ability of the oculomotor system to deal with multiple frequency components.
-
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.
-
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.
-
Treatments promoting post-stroke functional recovery continue to be an unmet therapeutic problem with physical rehabilitation being the most reproduced intervention in preclinical and clinical studies. Unfortunately, physiotherapy is typically effective at high intensity and early after stroke - requirements that are hardly attainable by stroke survivors. The aim of this study was to directly evaluate and compare the dose-dependent effect of delayed physical rehabilitation (daily 5 h or overnight voluntary wheel running; initiated on post-stroke day 7 and continuing through day 21) on recovery of motor function in the mouse photothrombotic model of ischemic stroke and correlate it with angiogenic potential of the brain. ⋯ Western blotting and immunofluorescence microscopy experiments evaluating the expression of angiogenesis-associated proteins VEGFR2, doppel and PDGFRβ in the peri-infarct and corresponding contralateral motor cortices indicate substantial upregulation of these proteins (≥2-fold) in the infarct core and surrounding cerebral cortex in the overnight running mice on post-stroke day 21. These findings indicate that there is a dose-dependent relationship between the extent of voluntary exercise, motor recovery and expression of angiogenesis-associated proteins in this expert-recommended mouse ischemic stroke model. Notably, our observations also point out to enhanced angiogenesis and presence of pericytes within the infarct core region during the chronic phase of stroke, suggesting a potential contribution of this tissue area in the mechanisms governing post-stroke functional recovery.