Neuroscience
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Evaluation of stimulus salience is critical for any higher organism, as it allows for prioritizing of vital information, preparation of responses, and formation of valuable memory. The paraventricular nucleus of the thalamus (PVT) has recently been identified as an integrator of stimulus salience but the neurochemical basis and afferent input regarding salience signaling have remained elusive. Here we report that neuropeptide S (NPS) signaling in the PVT is necessary for stimulus salience encoding, including aversive, neutral and reinforcing sensory input. ⋯ The PVT appears to provide stimulus salience encoding in a dose- and NPS-dependent manner. PVT NPSR1 neurons recruit the nucleus accumbens shell and structures in the prefrontal cortex and amygdala, which were previously linked to the brain salience network. Overall, these results demonstrate that stimulus salience encoding is critically associated with NPS activity in the PVT.
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The neurotrophin receptor p75 (p75NTR) is a circadian rhythm regulator and mediates cognitive deficits induced by sleep deprivation (SD). The soluble extracellular domain of p75NTR (p75ECD) has been shown to exert a neuroprotective function in Alzheimer's disease (AD) and depression animal models. Nevertheless, the role of p75ECD in SD-induced cognitive dysfunction is unclear. ⋯ The results revealed that peripheral supplementation of high-dose p75ECD-Fc (10 mg/kg) recovered the balance between Aβ and p75ECD in the hippocampus and rescued the cognitive deficits in SD mice. We also found that p75ECD-Fc ameliorated other pathologies induced by SD, including neuronal apoptosis, synaptic plasticity impairment and neuroinflammation. The current study suggests that p75ECD-Fc is a potential candidate for SD and peripheral supplementation of p75ECD-Fc may be a prospective preventive measure for cognitive decline in SD.
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To determine detrimental effects of estrogen and insulin deficiencies on hippocampus, we examined apoptosis-induced neuronal damage and cholinergic system in ovariectomized and/or diabetic rat hippocampus. Possible neuroprotective effects of treadmill exercise were also investigated. Adult female Wistar rats were randomly divided into four groups (n = 5 rats/group) as follows: control, ovariectomized (Ovx), diabetic (Dia, streptozotocin (STZ) 60 mg/kg; i.p.), and Ovx + Dia groups. ⋯ Treadmill exercise attenuated apoptosis-induced neuropathology in the Ovx and Dia groups and recovered AChE activity in the Dia group. Neuroprotective effects of treadmill exercise were mediated by inhibition of apoptosis. Moderate exercise protocol had no beneficial anti-apoptotic and neuroprotective effects in ovariectomized-diabetic rats.
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Tone-evoked synaptic excitation and inhibition are highly correlated in many neurons with V-shaped tuning curves in the primary auditory cortex of pentobarbital-anesthetized rats. In contrast, there is less correlation between spontaneous excitation and inhibition in visual cortex neurons under the same anesthetic conditions. However, it was not known whether the primary auditory cortex resembles visual cortex in having spontaneous excitation and inhibition that is less correlated than tone-evoked excitation and inhibition. ⋯ We use the ratio of the excitatory event rate to the inhibitory event rate, and the assumption that the excitatory and inhibitory synaptic currents can each be reasonably described as a filtered Poisson process, to estimate the maximum spontaneous excitatory-inhibitory correlation for each neuron. In a subset of neurons, we also measured tone-evoked excitation and inhibition. In neurons with V-shaped tuning curves, although tone-evoked excitation and inhibition were highly correlated, the spontaneous inhibitory event rate was typically sufficiently lower than the spontaneous excitatory event rate to indicate a lower excitatory-inhibitory correlation for spontaneous activity than for tone-evoked responses.
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To date, the mechanism of central fatigue during high-intensity exercise has remained unclear. Here we elucidate the central mechanisms of cardiovascular regulation during high-intensity exercise with a focus on the hypothesis that amygdala activation acts to limit maximum exercise performance. In the first of three experiments, we probed the involvement of the central nucleus of the amygdala (CeA) in such regulation. ⋯ We have found that (1) CeA lesions resulted in an increase in the total exercise time and the time at which an abrupt increase in arterial pressure appeared, indicating an apparent suppression of fatigue. (2) We confirmed that high-intensity exercise activated both the PVN-NTS and CeA-NTS pathways. Moreover, we discovered that (3) while stimulation of the CeA or PVN alone both induced pressor responses, their simultaneous stimulation also increased muscle vascular resistance. These results are evidence that cardiovascular responses during high-intensity exercise are affected by CeA activation, which acts to limit maximum exercise performance, and may implicate autonomic control modulating the PVN-NTS pathway via the CeA.