Neuroscience
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Parkinson's disease (PD) related to homozygous mutations in the Pink1 gene is associated with nigrostriatal dopamine depletion and a wide range of sensorimotor deficits. In humans and animal models of PD, not all sensorimotor deficits are levodopa-responsive. We hypothesized that the underlying mechanisms of locomotion, limb control, and vocal communication behavior include other pathologies. ⋯ Pearson's correlations showed that increases in time to traverse a tapered balance beam are significantly associated with reductions in striatal dopamine. Ultrasonic vocalization complexity was positively correlated with LC norepinephrine concentrations. These data support the evolving hypothesis that differences in neural substrates and early-onset noradrenergic mechanisms in the brainstem may contribute to pathogenesis in the Pink1 -/- rat.
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Following peripheral nerve injury, Schwann Cells (SCs) undergo dedifferentiation, proliferation, migration, and remyelination. Recent works demonstrated the importance of the short non-coding RNA (miRNAs) in SC dedifferentiation and remyelination after nerve injury. Previously, we found some miRNAs like miR-9, miR-221, miR-222 and miR-182 could regulate the proliferation and migration of SCs. ⋯ In addition, NGF1-A binding protein 1 (Nab1) which was essential for SCs myelination could be downregulated by miR-221-3p. Suppressing the expression of Nab1 could reverse the promotion of miR-221-3p antagomir on SC myelination. The effects of miR-221-3p on SC myelination might be used to improve peripheral nerve regeneration, thus offering a new approach to peripheral nerve repair.
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Survival depends on adaptation to shifting environmental risks and opportunities. Regarding risks, the mechanisms which permit acquisition, recall, and flexible use of aversive associations is poorly understood. Drawing on the evidence that the orbital frontal cortex is critical to integrating outcome expectancies with flexible appetitive behavioral responses, we hypothesized that OFC would contribute to behavioral flexibility within an aversive learning domain. ⋯ In a recall test, rats exhibit greater freezing to the CS+ than the CS-. Temporary inactivation of the ventrolateral OFC with muscimol prior to conditioning did not affect later discrimination, but inactivation after learning and prior to recall impaired discrimination between safety and danger cues. This result complements prior research in the appetitive domain and suggests that the OFC plays a general role in behavioral flexibility regardless of the valence of the CS.
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Slow-wave activity (SWA) in the electroencephalogram during slow-wave sleep (SWS) varies as a function of sleep-wake history. A putative sleep-active population of neuronal nitric oxide synthase (nNOS)-containing interneurons in the cerebral cortex, defined as such by the expression of Fos in animals euthanized after protracted deep sleep, may be a local regulator of SWA. We investigated whether electrophysiological responses to activation of these cells are consistent with their role of a local regulator of SWA. ⋯ Optogenetic stimulation of the cerebral cortex of animals expressing Channelrhodopsin2 in nNOS interneurons triggered an acute positive deflection of the local field potential that was followed by protracted oscillatory events only during quiet wake and slow wave sleep. The response during wake was maximal when the electroencephalogram (EEG) was in a negative polarization state and abolished when the EEG was in a positive polarization state. Since the polarization state of the EEG is a manifestation of slow-wave oscillations in the activity of underlying pyramidal neurons between the depolarized (LFP negative) and hyperpolarized (LFP positive) states, these data indicate that sleep-active cortical neurons expressing nNOS function in sleep slow-wave physiology.
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It has been shown that brain-injured patients (BIP) have exacerbated mirror movements (MM). MM are involuntary contractions occurring in homologous muscles contralateral to voluntary movements, particularly in distal upper limb muscles. Attentional and inhibitory processes have been proposed as key factors to explain the level of MM. ⋯ Moreover, (3) in all participants - independent of the type of task used to evaluate MM - the amount and intensity of MM was predicted by the level of executive control, assessed by the Trail Making Test. High level of MM was associated with weak executive control abilities. This study is the first to highlight the link between MM and executive functioning, which may have implications for rehabilitation in BIP.