Neuroscience
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To define whether cortical glutamatergic and GABAergic release machineries can be differentiated on the basis of the nature and amount of proteins they express, we studied the degree of co-localization of synaptogyrin (SGYR) 1 and 3, vesicle-associated membrane protein (VAMP) 1 and 2, syntaxin (STX) 1A and 1B in vesicular glutamate transporter (VGLUT)1-, VGLUT2- and vesicular GABA transporter (VGAT)-positive (+) puncta and synaptic vesicles in the rat cerebral cortex. Co-localization studies showed that SGYR1 and 3 were expressed in about 90% of VGLUT1+, 70% of VGLUT2+ and 80% of VGAT+ puncta; VAMP1 was expressed in approximately 45% of VGLUT1+, 55% of VGLUT2+, and 80% of VGAT+ puncta; VAMP2 in about 95% of VGLUT1+, 75% of VGLUT2+, and 80% of VGAT+ puncta; STX1A in about 65% of VGLUT1+, 30% of VGLUT2+, and 3% of VGAT+ puncta, and STX1B in approximately 45% of VGLUT1+, 35% of VGLUT2+, and 70% of VGAT+ puncta. ⋯ Moreover, we studied the localization of STX1B at the electron microscope and found that a population of axon terminals forming symmetric synapses were STX1B-positive. These results extend our previous observations on the differential expression of presynaptic proteins involved in neurotransmitter release in GABAergic and glutamatergic terminals and indicate that heterogeneity of glutamatergic and GABAergic release machinery can be contributed by both the presence or absence of a given protein in a nerve terminal and the amount of protein expressed by synaptic vesicles.
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The recently discovered exchange protein directly activated by cAMP (Epac), a guanine exchange factor for the G-protein RAP-1, is directly activated by cAMP independently of protein kinase A (PKA). While cAMP is known to be an important second messenger in the retina, the presence of Epac has not been investigated in this tissue. The goal of the present study was to determine if the Epac1 and Epac2 genes are present and to characterize their location within the retina. ⋯ Uniquely, Epac2 was expressed by cone photoreceptor inner and outer segments, cell bodies, and synaptic terminals. In contrast, Epac1 was expressed in vesicular glutamate transporter 1 (VGlut1) and C-terminal binding protein 2 (CtBP2) positive photoreceptor synaptic terminals. Together, these results provide evidence that Epac1 and Epac2 are differentially expressed within the retina and provide the framework for further functional studies of cAMP pathways within the retina.
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Noradrenaline (NA) microinjected into the rostromedial preoptic area (POA) elicits heat loss responses and opposes prostaglandin E(2)-induced fever. Here, I tested the hypothesis that local synthesis and release of nitric oxide (NO) mediates the NA-induced effects. ⋯ Furthermore, the NA-induced hypothermic responses were largely blocked by a prior microinjection of an NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 5 nmol), but not by that of its inactive enantiomer, N(G)-monomethyl-D-arginine (D-NMMA, 5 nmol), at the same site. These results suggest that the hypothermic and antipyretic effects of NA are mediated by NO in the rostromedial POA.
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Many neurological diseases result in a severe inability to reach for which there is no proven therapy. Promising new interventions to address reaching rehabilitation using robotic training devices are currently under investigation in clinical trials but the neural mechanisms that underlie these interventions are not understood. Transcranial magnetic stimulation (TMS) may be used to probe such mechanisms quickly and non-invasively, by mapping muscle and movement representations in the primary motor cortex (M1). ⋯ Movement vectors remained relatively constant (limited to <90 degrees section of the planar field) within some subjects across the entire map, while others covered a wider range of directions. This may be due to individual differences in cortical physiology or anatomy, resulting in a practical limit to the areas that are TMS-accessible. This study provides a baseline inventory of possible TMS-evoked arm movements in the robotic reaching trainer, and thus may provide a real-time, non-invasive platform for neurophysiology based evaluation and therapy in motor rehabilitation settings.
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The prefrontal cortex plays a key role in the perception of painful stimuli, including those emerging from the viscera. Colorectal distension is a non-invasive stimulus used to study visceral pain processing in the nervous system. Visceral hypersensitivity is one of the main characteristics of the functional bowel disorder irritable bowel syndrome (IBS). ⋯ However, an exaggerated cell activation was found in the prelimbic, infralimbic and rostral anterior cingulate cortices of the WKY rat compared to SD animals. No significant difference was found in caudal anterior cingulate cortex activation when the strains were compared. These results demonstrate, to our knowledge, for the first time an augmented colorectal distension-induced prefrontal cortex activity in WKY rats similar to that seen in IBS patients, further supporting the use of this strain as a model in which to study brain-gut axis dysregulation observed in IBS.