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RTT patients show periodical hypoventilation attacks. The breathing disorder contributing to the high incidence of sudden death is thought to be due to depressed central inspiratory (I) activity via unknown cellular processes. Demonstration of such processes may lead to targets for pharmacological control of the RTT\u2010type hypoventilation. We performed in vivo recordings from medullary respiratory neurons on the RTT rat model. To our surprise, both I and expiratory (E) neurons in the ventral respiratory column (VRC) increased their firing activity in <jats:italic>Mecp2<\/jats:italic>\u2010null rats with severe hypoventilation. These I neurons including E\u2013I phase\u2010spanning and other I neurons remained active during apneas. Consistent with enhanced central I drive, ectopic phrenic discharges during expiration as well as apnea were observed in the <jats:italic>Mecp2<\/jats:italic>\u2010null rats. Considering the increased I neuronal firing and ectopic phrenic activity, the RTT\u2010type hypoventilation does not seem to be caused by depression in central I activity, neither reduced medullary I premotor output. This as well as excessive E neuronal firing as shown in our previous studies suggests inadequate synaptic inhibition for phase transition. We found that the abnormal respiratory neuronal firing, ectopic phrenic discharge as well as RTT\u2010type hypoventilation all can be corrected by enhancing GABAergic inhibition. More strikingly, <jats:italic>Mecp2<\/jats:italic>\u2010null rats reaching humane endpoints with severe hypoventilation can be rescued by GABAergic augmentation. Thus, defective GABAergic inhibition among respiratory neurons is likely to play a role in the RTT\u2010type hypoventilation, which can be effectively controlled with pharmacological agents.<\/jats:p>","DOI":"10.1002\/jcp.30462","type":"journal-article","created":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T00:35:02Z","timestamp":1622680502000},"page":"8082-8098","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["In vivo evidence for the cellular basis of central hypoventilation of Rett syndrome and pharmacological correction in the rat model"],"prefix":"10.1002","volume":"236","author":[{"given":"Yang","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Biology Georgia State University Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ningren","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Biology Georgia State University 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