Neuroscience
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Alterations in thalamic GABAergic signaling are implicated in mediating the rise in 12-30 Hz electroencephalogram (EEG) activity that signals anesthetic-induced loss-of-consciousness with GABAA receptor-targeting general anesthetics. A number of modeling studies have identified that anesthetic-induced alterations in thalamocortico-corticothalamic signaling in the same network that generates sleep spindles would be sufficient to elicit this key EEG signature of anesthetic hypnosis with general anesthetic agents. Accordingly, we hypothesize that targeted stimulation of this thalamic GABAergic circuitry into a sleep-spindle mode of activity would promote the general anesthetic effects of etomidate. ⋯ Optical spindle-rhythm stimulation prolonged the increase in 12-30 Hz activity in ChR2-VGAT mice only (p = 0.023). Spindle-rhythm stimulation also increased the incidence and duration of sleep spindle-like oscillations in ChR2-VGAT mice only (all p ≤ 0.001). Despite the maintained anesthetic-like changes in EEG activity, optical spindle-rhythm stimulation was not associated with changes in the time to and duration of the loss-of-righting reflex, a behavioral endpoint of etomidate-induced general anesthesia in rodents.
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Spike sorting is an essential step in extracting neuronal discharge patterns which help to decode different activities in the neural system. Therefore, improving the spike sorting accuracy can improve neural decoding performance subsequently. Although many methods are suggested for spike sorting, few studies have evaluated their effect on neural decoding performance. ⋯ In the simulation study, the proposed spike sorting algorithm based on optimized wavelet parameter selection outperformed both the WaveClus spike sorting and traditional PCA-based spike sorting algorithms. The results showed the superiority of the spike sorting algorithm based on optimal wavelet parameters compared to classical discrete wavelet transform (DWT) or PCA-based spike sorting methods in decoding real intracortical data. Overall, the results indicate that it is possible to improve neural decoding performance by improving the spike sorting accuracy.
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Although conditioned pain modulation (CPM) is considered to represent descending pain inhibitory mechanisms triggered by noxious stimuli applied to a remote area, there have been no previous studies comparing CPM between pain and tactile systems. In this study, we compared CPM between the two systems objectively using blink reflexes. Intra-epidermal electrical stimulation (IES) and transcutaneous electrical stimulation (TS) were applied to the right skin area over the supraorbital foramen to evoke a nociceptive or a non-nociceptive blink reflex, respectively, in 15 healthy males. ⋯ Both the NRS score and nociceptive R2 were significantly decreased in the third session for IES, with a significant correlation between the two variables; whereas, TS-induced non-nociceptive R2 did not change among the sessions. Although the conditioning stimulus decreased the NRS score for TS, the CPM effect was significantly smaller than that for IES (p = 0.002). The present findings suggest the presence of a pain-specific CPM effect to a heterotopic noxious stimulus.
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Mitochondrial permeability transition pore (mPTP) opening is critical to mitochondrial apoptosis during ischemic injury. Sirtuin 3 (Sirt3) is a mitochondrial deacetylase known to play a major role in stress resistance and cell death. Our previous studies have shown that Sirt3 activates superoxide dismutase 2 and forkhead box O3a to reduce cellular reactive oxygen species. ⋯ Sirt3 overexpression suppressed the increase in VDAC1, ANT1 and cleaved caspase 3 that were induced by the serum and glucose deprivation (SGD) condition. Our studies suggest that ischemic injury induced mPTP opening and apoptosis by reducing Sirt3. It helps to identify new therapeutic targets for ischemic stroke.