{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:37:41Z","timestamp":1791398261619,"version":"4.3.3"},"reference-count":57,"publisher":"American Physiological Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2013,12,1]]},"abstract":"<jats:p> Rett syndrome (RTT) is a neurodevelopmental disorder with symptoms starting 6\u201318 mo after birth, while what underlies the delayed onset is unclear. Allopregnanolone (Allop) is a metabolite of progesterone and a potent modulator of GABA<jats:sub>A<\/jats:sub>-ergic currents whose defects are seen in RTT. Allop changes its concentration during the perinatal period, which may affect central neurons via the GABA<jats:sub>A<\/jats:sub>-ergic synaptic transmission, contributing to the onset of the disease. To determine whether Mecp2 disruption affects Allop modulation, we performed studies in brain slices obtained from wild-type (WT) and Mecp2<jats:sup> \u2212\/Y<\/jats:sup> mice. Allop dose dependently suppressed locus coeruleus (LC) neuronal excitability in WT mice, while Mecp2-null neurons showed significant defects. Using optogenetic approaches, channelrhodopsin was specifically expressed in GABA-ergic neurons in which optical stimulation evoked action potentials. In LC neurons of WT mice, Allop exposure increased the amplitude of GABA<jats:sub>A<\/jats:sub>-ergic inhibitory postsynaptic currents (IPSCs) evoked by optical stimulation and prolonged the IPSC decay time. Consistently, Allop augmented both frequency and amplitude of GABA<jats:sub>A<\/jats:sub>-ergic spontaneous IPSCs (sIPSCs) and extended the decay time of sIPSCs. The Allop-induced potentiation of sIPSCs was deficient in Mecp2<jats:sup> \u2212\/Y<\/jats:sup> mice. Surprisingly, the impairment occurred at 3 wk postnatal age, while no significant difference in Allop modulation was observed in 1\u20132 wk between WT and Mecp2<jats:sup> \u2212\/Y<\/jats:sup> mice. These results indicate that the modulation of GABA<jats:sub>A<\/jats:sub>-ergic synaptic transmission by Allop is impaired in LC neurons of Mecp2-null mice at a time when RTT-like symptoms manifest, suggesting a potential mechanism for the delayed onset of the disease. <\/jats:p>","DOI":"10.1152\/ajpcell.00195.2013","type":"journal-article","created":{"date-parts":[[2013,9,26]],"date-time":"2013-09-26T04:44:54Z","timestamp":1380170694000},"page":"C1151-C1160","source":"Crossref","is-referenced-by-count":21,"title":["Time-dependent modulation of GABA<sub>A<\/sub>-ergic synaptic transmission by allopregnanolone in locus coeruleus neurons of <i>Mecp2<\/i>-null mice"],"prefix":"10.1152","volume":"305","author":[{"given":"Xin","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Biology, Georgia State University, Atlanta, 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