Neuroscience
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To understand neuronal information processing, it is essential to investigate the input-output relationship and its modulation via detailed dissections of synaptic transmission between pre- and postsynaptic neurons. In Caenorhabditis elegans, pre-exposure to an odorant for five minutes reduces chemotaxis (early adaptation). AWC sensory neurons and AIY interneurons are crucial for this adaptation; AWC neurons sense volatile odors, and AIY interneurons receive glutamatergic inputs from AWC neurons. ⋯ Adaptation in the Ca2+ signal measured in AIY neurons is caused by adaptation in glutamate release from AWC neurons. Further, we found that a G protein γ-subunit, GPC-1, is related to modulation of glutamate input to AIY. Our results dissect the modulation of the pre- and postsynaptic relationship in vivo based on optical methods, and demonstrate the importance of neurotransmitter-release modulation in presynaptic neurons without Ca2+ modulation.
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C1q/TNF-related Protein 4 (CTRP4) has been reported to decrease food intake and regulate energy homeostasis. However, its underlying mechanism and signaling pathway remain unknown. Using an adenovirus-mediated hypothalamic CTRP4 overexpression model, we investigated the impact of CTRP4 on food intake and signal transducer and activator of transcription 3 (STAT3) signaling pathway in normal chow-fed mice. ⋯ The changes of neuropeptides were accompanied by significant increased STAT3 phosphorylation and decreased SOCS3 levels. The same changes of neuropeptides and STAT3 signaling were also found in N2a cells after CTRP4 overexpression intervention. Collectively, our data reveals that CTRP4 induces the activation of STAT3 signaling and decreases food intake.
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Glycosphingolipids (GSLs) are abundant, ceramide-containing lipids in the nervous system that play key functional roles in pain and inflammation. We measured gene expression (Ugcg, St3gal5, St8sia1, B4galNT1, Ugt8a, and Gal3st1) of glycosyltransferases involved in GSL synthesis in murine dorsal root ganglion (DRG) and spinal cord after complete Freund's adjuvant (CFA)-induced unilateral hind-paw inflammation (1 day vs. 15 days). Chronic inflammation (15 days) sensitized both ipsilateral and contralateral paws to pain. ⋯ Since intrathecal injection of b-series ganglioside induced mechanical allodynia in naïve mice, it seems reasonable that b-series gangliosides synthesized from upregulated St8sia1 in the ipsilateral spinal cord are involved in mechanical allodynia. By contrast, chronic inflammation led to a decrease of Ugcg, St3gal5, B4galnt1, and Gal3st1 expression in spinal cord bilaterally and an increase of St8sia1 expression in the ipsilateral DRG, suggesting that a-/b-series gangliosides in the spinal cord decreased and b-series gangliosides in ipsilateral DRG increased. These changes in glycosyltransferase gene expression in the DRG and the spinal cord may contribute to the modification of pain sensitivity in both inflamed and non-inflamed tissues and the transition from early to chronic inflammatory pain.
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Growing evidence indicates that GABAergic interneurons play a pivotal role to generate brain oscillation patterns, which are fundamental for the mnemonic processing of the hippocampus. While acetylcholine (ACh) is a powerful modulator of synaptic plasticity and brain function, few studies have been focused on the role of cholinergic signaling in the regulation of GABAergic inhibitory synaptic plasticity. ⋯ These forms of iLTP are blocked by the M1 type of mAChR (MR1) or by the group I of mGluR (mGluR1/5) antagonists. These results suggest the existence of spatiotemporal cooperativity between cholinergic and glutamatergic pathways where activation of mAChR serves as a metaplastic switch making glutamatergic synapses capable to induce long-term potentiation at inhibitory synapses, that may contribute to the modulation of brain mechanisms of learning and memory.
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Some individuals recover from the pain of nerve trauma within 12 months or less whereas others experience life-long intractable pain. This transition between reversible pain and the establishment of chronic neuropathic pain is poorly understood. We examined the role of persistent inflammation in the dorsal root ganglia (DRG) in the long-term maintenance of mechanical allodynia; an index of neuropathic pain. ⋯ These data support the hypothesis that the amount of CSF1 immunoreactivity and the persistence of inflammation in ipsilateral DRGs contribute to the difference between transient and persistent mechanical allodynia observed in the CCI and SNI models. We also suggest that feedback loops involving cytokines and neurotransmitters may contribute to increased DRG activity in chronic neuropathic pain. Consequently, targeting persistent CSF1 production and peripheral neuroinflammation may be an effective approach to the management of chronic neuropathic pain.