Neuroscience
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Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that has been implicated in energy homeostasis. Pharmacological studies with MCH and its receptor antagonists have suggested additional behavioral roles for the neuropeptide in the control of mood and vigilance states. These suggestions have been supported by a report of modified sleep in the MCH-1 receptor knockout mouse. ⋯ Thus MCH(-)(/)(-) mice adapt poorly to fasting, and their loss of bodyweight under this condition is associated with behavioral hyperactivity and abnormal expression of REM sleep. These results support a role for MCH in vigilance state regulation in response to changes in energy homeostasis and may relate to a recent report of initial clinical trials with a novel MCH-1 receptor antagonist. When combined with caloric restriction, the treatment of healthy, obese subjects with this compound resulted in some subjects experiencing vivid dreams and sleep disturbances.
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Systemic administration of selective 5-HT1A agonists, such as 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OHDPAT), stimulates the electrical activity of ventral tegmental area (VTA) dopamine neurons by a mechanism which remains unknown. We have examined if this activation is dependent on glutamatergic, serotonergic and GABAergic neurotransmission and if 5-HT1A receptors located within the VTA or within the prefrontal cortex (PFC) could contribute. In vivo electrophysiological recordings were obtained from VTA dopamine neurons from anesthetized rats. ⋯ These results show that activation of midbrain dopamine neurons by the systemic administration of 5-HT1A agonists does involve the inactivation of a tonic GABAergic tone, involving mainly the GABAB receptors, probably leading to the stimulation of a glutamatergic excitatory drive from the PFC to the VTA and an increase in glutamate release. This will excite dopamine neurons, preferentially through NMDA receptors. Furthermore, our results suggest that some 5-HT1A receptors located within the VTA may also participate in this activation.
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Amputees may experience stump pain (SP), phantom limb (PL) sensations, pain, and/or a general awareness of the missing limb. The mechanisms underlying these perceptions could involve nervous system neuroplasticity and be reflected in altered sensory function of the residual limb. Since little is known about the progression of post-amputation sensory phenomena over time, we longitudinally evaluated the stability of, and relationships among: 1) subjective reports of PL sensations, pain, awareness, and SP, 2) stump tactile and tactile spatial acuity thresholds, and 3) use of a functional vs. a cosmetic prosthesis in 11 otherwise healthy individuals with recent unilateral, traumatic upper-extremity amputation. ⋯ Initial SP correlated with follow-up SP, the initial PL pain correlated with follow-up PL pain but neither initial nor follow-up SP appear to be related to follow-up PL pain after accounting for initial PL pain intensity. Neither limb temperature nor prosthesis-use correlated with the initial vs. follow-up change in PL pain intensity. These data provide evidence that PL pain described 1-3 years after an amputation is not related in any simple way to peripheral sensory function, SP, or limb temperature; and PL awareness but not PL pain may be influenced by the frequent use of a functional prosthesis.
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The purpose of the present study was to verify our assumption that rhythmic respiratory activity may be regulated by endogenous hydrogen sulfide (H(2)S) in the medullary slices of neonatal rats. We found that a moderate concentration of donor of H(2)S, NaHS, mainly induced diphasic respiratory responses indicated by changes of discharge frequency (DF) of hypoglossal rootlets, an initial inhibitory stage followed by a later excitatory one. Cystathionine beta-synthase (CBS) substrate, cysteine (CYS), exerted similar effects. ⋯ Co-application of Gl and SQ eliminated both inhibitory and excitatory effect induced by NaHS. The cAMP level was increased in the later stage but not in the initial one by NaHS, and the increase in the cAMP level could be eliminated by SQ. It can be concluded that the endogenous H(2)S could be produced through the CBS-H(2)S pathway and could be involved in the control of the central rhythmic respiration in the in vitro medullary slices of neonatal rats by opening K(ATP) channels and activating AC-cAMP pathway of the neurons.
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Hereditary hearing loss is one of the most prevalent inherited human birth defects, affecting one in 2000. A strikingly high proportion (50%) of congenital bilateral nonsyndromic sensorineural deafness cases have been linked to mutations in the GJB2 coding for the connexin26. It has been hypothesized that gap junctions in the cochlea, especially connexin26, provide an intercellular passage by which K(+) are transported to maintain high levels of the endocochlear potential essential for sensory hair cell excitation. ⋯ Thus, morphological observations confirmed that a dominant-negative Gjb2 mutation showed incomplete development of the cochlear supporting cells. On the other hand, the development of the sensory hair cells, at least from P5 to P12, was not affected. The present study suggests that Gjb2 is indispensable in the postnatal development of the organ of Corti and normal hearing.