Neuroscience
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Under normal conditions, the acoustic pitch percept of a pure tone is determined mainly by the tonotopic place of the stimulation along the cochlea. Unlike acoustic stimulation, electric stimulation of a cochlear implant (CI) allows for the direct manipulation of the place of stimulation in human subjects. CI sound processors analyze the range of frequencies needed for speech perception and allocate portions of this range to the small number of electrodes distributed in the cochlea. ⋯ This trend was particularly apparent when the allocations of stimulus frequencies to electrodes were changed over time, with pitch changes even reversing direction in some subjects. These findings show that pitch plasticity can occur more rapidly and on a greater scale in the mature auditory system than previously thought possible. Overall, the results suggest that the adult auditory system can impose perceptual order on disordered arrays of inputs.
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Obesity resistance due to elevated orexin signaling is accompanied by high levels of spontaneous physical activity (SPA). The behavioral and neural mechanisms underlying this observation have not been fully worked out. We determined the contribution of hypothalamic orexin receptors (OXRs) to SPA stimulated by orexin A (OXA), whether OXA-stimulated SPA was secondary to arousal and whether voluntary wheel running led to compensations in 24-h SPA. ⋯ Obesity-resistant rats ran more and wheel running was directly related to 24-h SPA levels. The OX1R antagonist, SB-334867-A, and the DA1R antagonist, SCH3390, in SN more effectively reduced SPA stimulated by OXA in obesity-resistant rats. These data suggest OXA-stimulated SPA is not secondary to enhanced arousal, propensity for SPA parallels inclination to run and that orexin action on dopaminergic neurons in SN may participate in the mediation of SPA and running wheel activity.
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In female mammals, the postpartum period involves dramatic shifts in many socioemotional behaviors. This includes a suppression of anxiety-related behaviors that requires recent physical contact with offspring. Factors contributing to differences among females in their susceptibility to the anxiety-modulating effect of offspring contact are unknown, but could include their innate anxiety and brain monoaminergic activity. ⋯ There was no relationship between females' anxiety and dorsal raphe TPH2. Thus, a primary effect of recent contact with offspring on anxiety-related behavior in postpartum rats is to shift females away from their innate anxiety to a more moderate level of responding. This effect is particularly true for females with the lowest anxiety, may be mediated by central noradrenergic systems, and has implications for their ability to attend to their offspring.
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Progesterone (PROG) is promising as an important protective agent against various injuries to the nervous system. The present study was designed to investigate whether starting PROG administration, when symptomatology is already established, would alleviate the expression of nociceptive behaviors (mechanical allodynia and thermal hyperalgesia) and electrophysiological changes in a chronic constriction injury (CCI) model of neuropathic pain in rats. Male rats were given PROG (1.5, 3, 6 and 12 mg/kg, i.p.) 12 days after CCI induction, and dosing continued daily until day 26. ⋯ PROG at doses of 6 or 12 mg/kg induced a significant recovery of all electrophysiological changes. Our data indicated that starting PROG therapy when symptomatology is already established, and continuing it for a sufficient period of time, may have a therapeutic effect. This suggests that PROG may offer new strategies for the treatment of neuropathic pain.
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Neuropeptide Y (NPY) is present in the superficial laminae of the dorsal horn and inhibits spinal nociceptive processing, but the mechanisms underlying its anti-hyperalgesic actions are unclear. We hypothesized that NPY acts at neuropeptide Y1 receptors in the dorsal horn to decrease nociception by inhibiting substance P (SP) release, and that these effects are enhanced by inflammation. To evaluate SP release, we used microdialysis and neurokinin 1 receptor (NK1R) internalization in rat. ⋯ To determine the contribution of increased Y1 receptor-G protein coupling, we measured [(35)S]GTPγS binding simulated by [Leu(31), Pro(34)]-NPY in mouse dorsal horn. CFA inflammation increased the affinity of Y1 receptor G-protein coupling. We conclude that Y1 receptors contribute to the anti-hyperalgesic effects of NPY by mediating the inhibition of SP release, and that Y1 receptor signaling in the dorsal horn is enhanced during inflammatory nociception.