Neuroscience
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Parkinson disease (PD) is a leading neurodegenerative disease, with multifaceted interacting mechanisms. The Thy1-aSyn mouse model of PD exhibits many features of PD patients, including sensorimotor and olfactory dysfunction and protein aggregation. Here, we tested the hypothesis that the dipeptide carnosine, which has anti-aggregating and metal-chelating properties, would provide beneficial effects on the motor and olfactory deficits observed in Thy1-aSyn mice. ⋯ In contrast, intranasal carnosine prevented the normal decline in gait function seen in the challenging beam test in the Thy1-aSyn mice. Moreover, carnosine-treated Thy1-aSyn mice exhibited decreased aSyn immunostaining in the olfactory epithelium compared to vehicle-treated Thy1-aSyn mice, and the carnosine transporter Pept2 was immunolocalized to the apical surface of the olfactory epithelium. These findings demonstrate that intranasal carnosine shows promise in slowing the progression of motor deficits and aSyn deposition in PD.
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The ventrolateral periaqueductal gray matter (vlPAG) plays a critical role in the pathogenesis of migraine and few studies have shown that vlPAG might be involved in the pathophysiology of epilepsy. But its roles in epileptogenesis and comorbid relationship between migraine and epilepsy have never been reported. In this study, the impairments of vlPAG neuronal network during spontaneous recurrent seizure (SRS) development after status epilepticus (SE) were investigated, and the pain sensitivity as well as the SRS investigated after neurochemical lesion to vlPAG to determine the role of vlPAG in epileptogenesis and in migraine comorbidity with epilepsy. ⋯ On the other hand, neurochemical lesion to vlPAG enhanced frequency and duration of spontaneous seizure event and frequency of epileptiform inter-ictal spike discharges in electroencephalography (EEG), but decreased pain threshold in epileptic rats. This indicates an involvement of the pain regulating structure, vlPAG, in the pathogenesis of epilepsy. This may imply that vlPAG network alterations could be a possible underlying mechanism of the interactive comorbid relationship between epilepsy and migraine.
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Perceptual selection can be guided by the contents of working memory (WM). Neuroimaging and neuropsychological data point to a role of a fronto-parietal and fronto-thalamic networks in WM guidance. Here we assessed the effect of transcranial direct current stimulation of the left dorsal frontal cortex (lDFC) in a combined WM/attention paradigm. ⋯ Notably, across two experiments we found that lDFC-tDCS modulated WM guidance of visual selection in the context of high processing loads in WM. No effects of tDCS were observed in WM accuracy. These findings suggest that the role of the left dorsal frontal cortex in WM guidance is associated with selective attentional control rather than mnemonic processing.
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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.