Neuroscience
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Localization of sound sources in the environment requires neurons that extract interaural timing differences (ITD) in low-frequency hearing animals from fast and precisely timed converging inputs from both ears. In mammals, this is accomplished by neurons in the medial superior olive (MSO). MSO neurons receive converging excitatory input from both the ipsilateral and contralateral cochlear nuclei and glycinergic, inhibitory input by way of interneurons in the medial and lateral nuclei of the trapezoid body (MNTB and LNTB, respectively). ⋯ Herein, we utilized neuron reconstructions and immunohistochemistry to investigate the distribution of glutamatergic and glycinergic inputs onto human MSO neurons. Our results indicate that human MSO neurons have simple, symmetric dendrites and that glycinergic inputs outnumber glutamatergic inputs on MSO cell bodies and proximal dendrites. Together these results suggest that the human MSO utilizes similar circuitry to other mammals with excellent low-frequency hearing.
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Our previous work has linked childhood violence exposure in Black youth to functional changes in the hippocampus, a brain region sensitive to stress. However, different contexts of violence exposure (e.g., community, home, school) may have differential effects on circuitry. We investigated the unique effect of community violence in predicting resting-state functional connectivity (rsFC) in the hippocampus. ⋯ Age-related decreases in hippocampus-insula rsFC were also present in youth with lower violence exposure, but not in youth with higher violence exposure. This is one of the first studies to investigate the unique impact of community violence, above home and school violence, on threat circuitry. Our data suggest functional alterations in the hippocampus in violence-exposed youth, and that violence in the community may be a more salient form of threat exposure compared to other forms of violence experienced by youth.
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Since their discovery in the 1960s, the term paroxysmal depolarization shift (PDS) has been applied to a wide variety of reinforced neuronal discharge patterns. Occurrence of PDS as cellular correlates of electrographic spikes during latent phases of insult-induced rodent epilepsy models and their resemblance to giant depolarizing potentials (GDPs) nourished the idea that PDS may be involved in epileptogenesis. Both GDPs and - in analogy - PDS may lead to progressive changes of neuronal properties by generation of pulsatile intracellular Ca2+ elevations. ⋯ These PDS appear to be initiated in the dendritic sub-compartment. Their morphology critically depends on the position of recording electrodes and on their rate of occurrence. These results provide novel insight into induction mechanisms, origin, variability, and co-existence of PDS with other discharge patterns and thereby pave the way for future investigations regarding the role of PDS in epileptogenesis.
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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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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.