Neuroscience
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Widely correlated spontaneous activity in the developing nervous system is transiently expressed and is considered to play a fundamental role in neural circuit formation. The depolarization wave, which spreads over a long distance along the neuraxis, maximally extending to the lumbosacral cord and forebrain, is an example of this spontaneous activity. Although the depolarization wave is typically initiated in the spinal cord in intact preparations, spontaneous discharges have also been detected in the isolated brainstem. ⋯ The results revealed that the depolarization wave was homeostatically maintained, which was characterized by an increase in excitability and/or the number of neurons recruited to the wave. The wave was more easily maintained in younger embryos. Furthermore, we demonstrated that the ability of brainstem neurons to perform such an active compensation was not lost even at the stage when the depolarization wave was no longer observed in the intact brainstem.
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Fear conditioning has been proposed as an important factor involved in the etiology of posttraumatic stress disorder (PTSD). We examined fear processing in PTSD patients with mild symptoms and in individuals who did not develop symptoms (both groups consisting of victims of a bank robbery), through the study of fear-conditioned response. Conditioned responses were quantified by the skin conductance response (SCR) and the facial thermal response, the latter being measured by high-resolution functional thermal infrared (fIR) imaging. ⋯ These results, although preliminary, indicate that the analysis of SCR and facial thermal response during the conditioning paradigm is a promising psychometric method of investigation, even in the case of low level of PTSD symptom severity. To the best of our knowledge, this study is the first attempt to discriminate between control subjects and PTSD patients with mild symptoms through infrared thermal imaging. It may suggest feasible approaches for diagnostic screening in the early phases of the disorder and in the assessment of preventive measures and therapies.
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Missense mutation R192Q in the CACNA1A gene causes familial hemiplegic migraine type-1 (FHM1), a monogenic subtype of migraine with aura. Using knock-in (KI) gene targeting we introduced this mutation into the mouse gene and generated a transgenic mouse model to investigate basic mechanisms of migraine pathophysiology. While FHM1 R192Q KI trigeminal ganglia were previously shown to exhibit constitutive up-regulation of ATP-gated P2X3 receptors, little is known about the firing properties of trigeminal sensory neurons, which convey nociceptive inputs to higher brain centers. ⋯ Activation by α,β-methyl-ATP was associated with a transient cluster of action potentials, while capsaicin elicited more persistent firing. Using α,β-methyl-ATP or capsaicin, two functional classes of WT or KI neurons were distinguished according to the first spike latency, which suggests that a subgroup of neurons may be indirectly activated, probably via crosstalk between neurons and satellite glial cells. Thus, our results are consistent with reported facilitated trigeminal pain behavior of FHM1 R192Q KI mice.
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The suprachiasmatic nucleus (SCN) is typically considered our autonomous clock synchronizing behavior with physiological parameters such as blood pressure (BP), just transmitting time independent of physiology. Yet several studies show that the SCN is involved in the etiology of hypertension. Here, we demonstrate that the SCN is incorporated in a neuronal feedback circuit arising from the nucleus tractus solitarius (NTS), modulating cardiovascular reactivity. ⋯ Examining this possibility we observed that elevation of BP, induced by α1-agonist infusion, was more than twice the magnitude in SCN-lesioned animals as compared to in controls, indicating indeed an active involvement of the SCN in short-term BP regulation. We propose that the SCN receives BP information directly from the NTS enabling it to react to hemodynamic perturbations, suggesting the SCN to be part of a homeostatic circuit adapting BP response. We discuss how these findings could explain why lifestyle conditions violating signals of the biological clock may, in the long-term, result in cardiovascular disease.
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Synaptosomal-associated protein of 25kDa (SNAP25), vesicle-associated membrane protein 1 (VAMP1) and 2 (VAMP2) are components of soluble N-ethylmaleimide-sensitive fusion attachment protein receptors (SNARE) complex which is involved in synaptic vesicle exocytosis, a fundamental step in neurotransmitter release. SNARE expression in cerebellum correlates with specific neurotransmitter pathways underlying synaptic diversification and defined synaptic properties. In this study we firstly characterized the distribution of SNAP25, VAMP1 and VAMP2 in the nerve terminals of a defined cerebellar region, the deep cerebellar nuclei (DCN), of adult and newborn rats. ⋯ Results showed that: (1) distribution of SNAP25, VAMP1 and VAMP2 in adult DCN differs significantly from that found in newborn DCN; (2) administration of E2 in the newborn DCN affected synaptic density and also changed the distribution of the pre- and postsynaptic proteins. The differential distribution of SNAP25, VAMP1 and VAMP2 in nerve terminals of adult and newborn rats may correlate with specific stages of neuronal phenotypic differentiation. The effects of E2 on SNAP25, VAMP1, VAMP2, PDS95 and synaptic density suggest that pre- and postsynaptic proteins are under estrogenic control during development and that synaptic maturation can also be related with the activity of this steroid.