Cholinergic Synaptic Homeostasis Is Tuned by an NFAT-Mediated ?7 nAChR-Kv4/Shal Coupled Regulatory System.

ABSTRACT: 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 ?7 (D?7) 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 D?7 nAChRs, and this upregulation of D?7 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.

SUBMITTER: Eadaim A 

PROVIDER: S-EPMC7521586 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature