Cholinergic Synaptic Homeostasis Is Tuned by an NFAT-Mediated α7 nAChR-K(v)4/Shal Coupled Regulatory System.
Cholinergic Synaptic Homeostasis Is Tuned by an NFAT-Mediated α7 nAChR-K(v)4/Shal Coupled Regulatory System.
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DOI：
10.1016/j.celrep.2020.108119
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发表时间：
2020-09-08
期刊：
影响因子：
8.8
通讯作者：
Tsunoda S
中科院分区：
文献类型：
--
作者：
Eadaim A;Hahm ET;Justice ED;Tsunoda S
Homeostatic synaptic plasticity (HSP) involves compensatory mechanisms employed by neurons and circuits to preserve signaling when confronted with global changes in activity that may occur during physiological and pathological conditions. Cholinergic neurons, which are especially affected in some pathologies, have recently been shown to exhibit HSP mediated by nicotinic acetylcholine receptors (nAChRs). In Drosophila central neurons, pharmacological blockade of activity induces a homeostatic response mediated by the Drosophila α7 (Dα7) nAChR, which is tuned by a subsequent increase in expression of the voltage-dependent Kv4/Shal channel. Here, we show that an in vivo reduction of cholinergic signaling induces HSP mediated by Dα7 nAChRs, and this upregulation of Dα7 itself is sufficient to trigger transcriptional activation, mediated by nuclear factor of activated T cells (NFAT), of the Kv4/Shal gene, revealing a receptor-ion channel system coupled for homeostatic tuning in cholinergic neurons. Eadaim et al. show that in vivo reduction of cholinergic signaling in Drosophila neurons induces synaptic homeostasis mediated by Dα7 nAChRs. This upregulation of Dα7 induces Kv4/Shal gene expression mediated by nuclear factor of activated T cells (NFAT), revealing a receptor-ion channel system coupled for homeostatic tuning in cholinergic neurons.
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