Neuroscience
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It is well established that the primary motor cortex (M1) plays a significant role in motor learning in healthy humans. It is unclear, however, whether mechanisms of motor learning include M1 oscillatory activity. In this study, we aimed to test whether M1 oscillations, entrained by transcranial Alternating Current Stimulation (tACS) at motor resonant frequencies, have any effect on motor acquisition and retention during a rapid learning task, as assessed by kinematic analysis. ⋯ At the end of training, corticospinal excitability had similarly increased in the three sessions. The results are compatible with the hypothesis that entrainment of the two major motor resonant rhythms through tACS over M1 has different effects on motor learning in healthy humans. The effects, however, were unrelated to corticospinal excitability changes.
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Acetylcholine (ACh) is an abundant neurotransmitter and neuromodulator in many species. In Drosophila melanogaster ACh is the neurotransmitter used in peripheral sensory neurons and is a primary excitatory neurotransmitter and neuromodulator within the central nervous system (CNS). The receptors that facilitate cholinergic transmission are divided into two broad subtypes: the ionotropic nicotinic acetylcholine receptors (nAChRs) and the metabotropic muscarinic acetylcholine receptors (mAChRs). ⋯ We combined this with targeted AChR RNAi-mediated knockdown to identify specific receptor subtypes facilitating ACh modulation of circuit efficacy. We identify a contribution by both mAChRs and nAChRs in regulation of locomotor behavior and reveal they play a role in modulation of the excitability of a sensory-CNS-motor circuit. We further reveal a conspicuous role for mAChR-A and mAChR-C in motor neurons in modulation of their input-output efficacy.
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Astrocytes regulate extracellular glutamate homeostasis in the central nervous system through the Na+-dependent glutamate transporters glutamate transporter-1 (GLT-1) and glutamate aspartate transporter (GLAST). Impaired astrocyte glutamate uptake could contribute to the development of epilepsy but the regulation of glutamate transporters in epilepsy is not well understood. In this study, we investigate the expression of GLT-1 and GLAST in the mouse intrahippocampal kainic acid (IHKA) model of temporal lobe epilepsy (TLE). ⋯ GLAST immunoreactivity was increased in specific layers at 1 and 3 days post-IHKA in the ipsilateral hippocampus. GLAST synaptosomal protein levels were significantly elevated at 30 days compared to 7 days post-IHKA in the ipsilateral hippocampus. Our findings suggest that astrocytic glutamate transporter dysregulation could contribute to the development of epilepsy.
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Pathological accumulation of tau protein in brain cells is the hallmark of a group of neurodegenerative diseases called tauopathies. Accumulation of tau protein begins years before the onset of symptoms, which include deficits in cognition, behavior and movement. The pre-symptomatic phase of tauopathy may be the best time to deliver disease-modifying treatments, but this is only possible if prognostic, pre-symptomatic biomarkers are identified. ⋯ Down-regulation of these microRNAs persisted at 53 weeks of age, when hTau mice exhibit cognitive deficits and advanced neuropathology. Bioinformatic analysis showed that these three microRNAs converge on pathways associated with neuronal signaling and phosphorylation of tau. Thus, these circulating microRNAs appear to reflect neuropathological change and are promising candidates in the development of biomarkers of pre-symptomatic tauopathy.
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Angiopoietin (Ang) is an angiogenic factor, but its neuroprotective and neurotrophic effects have recently come to light. Ang exerts neuroprotective effects by inhibiting neuronal apoptosis, protecting the blood-brain/blood-spinal cord barrier, reducing inflammation and promoting neovascularization. ⋯ In addition, Ang and vascular endothelial growth factor (VEGF) are known to interact in blood vessels in the nervous system and the combination of Ang and VEGF can mitigate the negative effects of VEGF, such as inflammation and local edema. These data indicated that Ang is a novel neuroprotective/neurotrophic factor, which may become a new tool for the treatment of nerve injury.