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Habituation without NMDA Receptor-Dependent Desensitization of Hering- Apnea Reflex in a Mecp2 [superscript + / -] Mutant Mouse Model of Rett Syndrome

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dc.contributor.author Song, Gang
dc.contributor.author Tin, Chung
dc.contributor.author Giacometti, Emanuela
dc.contributor.author Poon, Chi-Sang
dc.date.accessioned 2011-10-06T22:16:14Z
dc.date.available 2011-10-06T22:16:14Z
dc.date.issued 2011-05
dc.date.submitted 2011-01
dc.identifier.issn 1662-5145
dc.identifier.uri http://hdl.handle.net/1721.1/66199
dc.description.abstract Non-associative learning is a basic neuroadaptive behavior exhibited in almost all animal species and sensory modalities but its functions and mechanisms in the mammalian brain are poorly understood. Previous studies have identified two distinct forms of non-associative learning in the classic Hering–Breuer inflation reflex (HBIR) induced apnea in rats: NMDA receptor (NMDAR)-independent habituation in a primary vagal pathway and NMDAR-dependent desensitization in a secondary pontine pathway. Here, we show that abnormal non-associative learning of the HBIR may underlie the endophenotypic tachypnea in an animal model of Rett syndrome (RTT), an autism-spectrum disorder caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MECP2). Mecp2+/− [Mecp2 superscript + / -] symptomatic mice on a mixed-strain background demonstrated significantly increased resting respiratory frequency with shortened expiration and normal inspiratory duration compared with asymptomatic mutants and wild-type controls, a phenotype that is characteristic of girls with RTT. Low-intensity electrical stimulation of the vagus nerve elicited fictive HBIR with time-dependent habituation in both Mecp2+/− [Mecp2 superscript + / -] and wild-type mice. However, time-dependent desensitization of the HBIR was evidenced only in wild-type controls and asymptomatic mutant mice but was absent or suppressed in Mecp2+/− [Mecp2 superscript + / -] symptomatic mice or in wild-type mice after blockade of NMDAR with dizocilpine. Remarkably, ∼50% of the Mecp2+/− [Mecp2 superscript + / -] mice developed these X-linked phenotypes despite somatic mosaicism. Such RTT-like respiratory endophenotypes in mixed-strain Mecp2+/− [Mecp2 superscript + / -] mice differed from those previously reported in Mecp2-/y [Mecp2 superscript - / y] mice on pure C57BL/6J background. These findings provide the first evidence indicating that impaired NMDAR-dependent desensitization of the HBIR may contribute to the endophenotypic tachypnea in RTT. en_US
dc.description.sponsorship National Institutes of Health (U.S.) (Grant HL093225) en_US
dc.description.sponsorship National Institutes of Health (U.S.) (Grant HL067966) en_US
dc.description.sponsorship National Institutes of Health (U.S.) (Grant HL072849) en_US
dc.description.sponsorship National Institutes of Health (U.S.) (Grant HL079503) en_US
dc.description.sponsorship National Institutes of Health (U.S.) (Grant RR028241) en_US
dc.language.iso en_US
dc.publisher Frontiers Research Foundation en_US
dc.relation.isversionof http://dx.doi.org/10.3389/fnint.2011.00006 en_US
dc.rights Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. en_US
dc.source Frontiers en_US
dc.title Habituation without NMDA Receptor-Dependent Desensitization of Hering- Apnea Reflex in a Mecp2 [superscript + / -] Mutant Mouse Model of Rett Syndrome en_US
dc.type Article en_US
dc.identifier.citation Song, Gang et al. “Habituation without NMDA Receptor-Dependent Desensitization of Hering–Breuer Apnea Reflex in a Mecp2+/− Mutant Mouse Model of Rett Syndrome.” Frontiers in Integrative Neuroscience 5:6 (2011): n. pag. © 2011 Song, Tin, Giacometti and Poon en_US
dc.contributor.department Harvard University--MIT Division of Health Sciences and Technology en_US
dc.contributor.department Massachusetts Institute of Technology. Department of Biology en_US
dc.contributor.department Whitehead Institute for Biomedical Research en_US
dc.contributor.approver Poon, Chi-Sang
dc.contributor.mitauthor Song, Gang
dc.contributor.mitauthor Tin, Chung
dc.contributor.mitauthor Giacometti, Emanuela
dc.contributor.mitauthor Poon, Chi-Sang
dc.relation.journal Frontiers in Integrative Neuroscience en_US
dc.identifier.mitlicense PUBLISHER_POLICY en_US
dc.eprint.version Final published version en_US
dc.type.uri http://purl.org/eprint/type/JournalArticle en_US
eprint.status http://purl.org/eprint/status/PeerReviewed en_US
dspace.orderedauthors Song, Gang; Tin, Chung; Giacometti, Emanuela; Poon, Chi-Sang en


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