Neuroscience
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We previously characterized the organization of presympathetic-premotor neurons (PSPMNs), which send descending poly-synaptic projections with collaterals to skeletal muscle and the adrenal gland. Such neurons may play a role in shaping integrated adaptive responses, and many of them were found within well-characterized regions of noradrenergic cell populations suggesting that some of the PSPMNs are catecholaminergic. To address this issue, we used retrograde trans-synaptic tract-tracing with attenuated pseudorabies virus (PRV) recombinants combined with multi-label immunofluorescence to identify PSPMNs expressing tyrosine hydroxylase (TH). ⋯ Within SubC and the A7 cell group, about 70% of TH-ir neurons were PSPMNs, which was a significantly greater fraction of neurons than in the other brain regions we examined. These findings indicate that TH-ir neurons near the pontomesencephalic junction that are distributed across the LC, SubC, and the A7 may play a prominent role in somatomotor-sympathetic integration, and that the major functional role of the A7 and SubC noradrenergic cell groups maybe in the coordination of concomitant activation of somatomotor and sympathetic outflows. These neurons may participate in mediating homeostatic adaptations that require simultaneous activation of sympathetic and somatomotor nerves in the periphery.
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Motor, sensory, and autonomic abnormalities are reported for toll-like receptor 9 (TLR9) knock-out (KO) mice. However, a physiological role of TLR9 in the nervous system is largely unknown. Since altered synaptic transmission can contribute to sensory and motor abnormalities, we evaluated neuromuscular junction (NMJ) function and morphology of TLR9 KO mice. ⋯ This alteration may result from ACh-induced decline of acetylcholine receptor (AChR) expression resulting from increased frequency and amplitude of mEPCs. At the same time, excessive spontaneous vesicular ACh release may initiate retrograde suppression of excitation-secretion coupling. These data suggest a novel role of TLR9 in the development of the NMJ.
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17β-Estradiol (E2) crucially affects several processes in the hippocampus of both sexes. E2 acts upon estradiol receptors ERα and ERβ, influencing target gene expression and/or modulates intracellular signaling cascades. Another potent modulator of hippocampal function is nucleoside adenosine, the final product of ectonucleotidase cascade, enzymes which hydrolyze extracellular ATP to adenosine. ⋯ Selective ERα receptor agonist, PPT, induced upregulation of both the protein level and activity of eN, while application of selective ERβ receptor agonist, DPN, increased only the activity of eN. In both cases, E2 entered into the intracellular compartment and activated ER(s), which was demonstrated by membrane impermeable E2-BSA conjugate. Together these results imply that E2-induced effects on connectivity and functional properties of the hippocampal synapses may be in part mediated through observed effect on eN.
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Engrailed-2 (En2), a homeodomain transcription factor involved in regionalization and patterning of the midbrain and hindbrain regions has been associated to autism spectrum disorders (ASDs). En2 knockout (En2(-/-)) mice show ASD-like features accompanied by a significant loss of GABAergic subpopulations in the hippocampus and neocortex. Brain-derived neurotrophic factor (BDNF) is a crucial factor for the postnatal development of forebrain GABAergic neurons, and altered GABA signaling has been hypothesized to underlie the symptoms of ASD. ⋯ Increased levels of phosphorylated TrkB and decreased levels of p75 receptor were also detected in the neocortex of mutant mice. Accordingly, the expression of low density lipoprotein receptor (LDLR) and RhoA, two genes regulated via p75 was significantly altered in forebrain areas of mutant mice. These data indicate that BDNF signaling alterations might be involved in the anatomical changes observed in the En2(-/-) forebrain and suggest a pathogenic role of altered BDNF signaling in this mouse model of ASD.
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In homeotherms, the hypothalamus controls thermoregulatory and adaptive mechanisms in energy balance, sleep-wake and locomotor activity to maintain optimal body temperature. Orexin neurons may be involved in these functions as they promote thermogenesis, food intake and behavioral arousal, and are sensitive to temperature and metabolic status. How thermal and energy balance signals are integrated in these neurons is unknown. ⋯ Interestingly, in rats fed with western diet for 1 or 11weeks, orexin neurons had impaired synaptic and KATP response to warming. In summary, this study reveals several mechanisms underlying thermosensing in orexin neurons and their attenuation by western diet. Overeating induced by western diet may in part be due to impaired orexin thermosensing, as post-prandial thermogenesis may promote satiety and lethargy by inhibiting orexin neurons.