Neuroscience
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Genetic analyses have linked BTBD9 to restless legs syndrome (RLS) and sleep regulation. Btbd9 knockout mice show RLS-like motor restlessness. Previously, we found hyperactivity of cerebellar Purkinje cells (PCs) in Btbd9 knockout mice, which may contribute to the motor restlessness observed. ⋯ However, Syngap1 heterozygous knockout mice showed nocturnal, instead of diurnal, motor restlessness. Our results suggest that SYNGAP1 deficiency may not contribute directly to the RLS-like motor restlessness observed in Btbd9 knockout mice. Finally, we found that PC-specific Btbd9 knockout mice exhibited deficits in motor coordination and balance similar to Btbd9 knockout mice, suggesting that the motor effect of BTBD9 in PCs is cell-autonomous.
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We used the framework of the uncontrolled manifold hypothesis to explore force-stabilizing synergies and motor equivalence in the spaces of individual motor unit (MU) firing frequencies. Healthy subjects performed steady force production tasks by pressing with one finger or three fingers of a hand. Surface EMG was used to identify individual MU action potentials. ⋯ Effects of hand dominance were seen on multi-finger synergies but not intra-muscle synergies. We conclude that spinal mechanisms, such as recurrent inhibition and reflex loops from proprioceptors, contribute significantly to intra-muscle synergies, while multi-finger synergies reflect supra-spinal processes. These results provide methods to explore the contributions of spinal vs supraspinal circuitry to changed motor synergies in populations with a variety of neurological disorders.
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It has been shown that a previously consolidated memory can incorporate either new external information or a novel internal emotional state following a labile state induced by retrieval. This updating process allows editing unwanted fear memory, leading to the reduction of the fear response. Memory can be modulated by the circadian cycle. ⋯ However, three retrieval sessions in the dark cycle were able to update fear memory, reducing freezing response in the test performed in the light cycle. This effect was blocked when the glucocorticoid synthesis inhibitor metyrapone was administered before retrieval. This approach opens new avenues to explore interventions that consider the circadian cycle in the treatment of fear memories based on non-pharmacological interventions.
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Defective mitophagy and mitochondrial dysfunction have been linked to aging and Alzheimer's disease (AD). β2-Adrenergic receptor (ADRB2) is critical for mitochondrial and cognitive function. However, researchers have not clearly determined whether ADRB2 activation ameliorates defective mitophagy and cognitive deficits in individuals with AD. Here, we observed that the activation of ADRB2 by clenbuterol (Clen, ADRB2 agonist, 2 mg/kg/day) ameliorated amyloid-β-induced (Aβ1-42 bilateral intracerebral infusion, 2 μl, 5 μg/μl) memory deficits. ⋯ Finally, we established that Clen improved mitophagy and attenuated mitochondrial dysfunction, and tau pathology in mice by activating the ADRB2/Akt/PINK1 signaling pathway. Conversely, the inhibition of ADRB2 by propranolol (βAR antagonist, 10 μM) blocked the Clen-mediated improvements in pathological changes in N2a cells. The results from the present study indicate that ADRB2 activation may be a therapeutic strategy for AD.
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Because of different mechanism of electro-signaling in myelinated axons than in dendrites or unmyelinated axons, the role of the myelin needs to be reconsidered upon new premises in distinction to conventional cable model. It occurs that the latter model is inapplicable for so-called saltatory conduction in myelinated axons and the former imagination on the role of the myelin based on the cable model is confusing. ⋯ This is of particular importance for better understanding of malfunctions of neuron communication due to demyelination diseases and for the strategy of future therapy methods at paralysis and at demyelination syndromes. The new mechanism of signaling in myelinated neurons is also supported by recent advances in recognition of so-called micro-saltatory conduction in C-fibers of pain sensation, also exceeding the range of applicability of the conventional cable model.