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This study used the Bird mouse model of RTT to investigate sensory thalamocortical synaptic transmission in the barrel cortex of Mecp2-null mice. Electrophysiological results showed an excitation\/inhibition imbalance, biased toward inhibition, due to an increase in efficacy of postsynaptic GABA<jats:sub>A<\/jats:sub> receptors rather than alterations in inhibitory network and presynaptic release properties. Enhanced inhibition impaired the transmission of tonic sensory signals from the thalamus to the somatosensory cortex. Previous morphological studies showed an upregulation of NMDA receptors in the neocortex of both RTT patients and Mecp2-null mice at early ages [Blue ME, Naidu S, Johnston MV. Ann Neurol 45: 541\u2013545, 1999; Blue ME, Kaufmann WE, Bressler J, Eyring C, O'Driscoll C, Naidu S, Johnston MV. Anat Rec (Hoboken) 294: 1624\u20131634, 2011]. Although AMPA and NMDA receptor-mediated excitatory synaptic transmission was not altered in the barrel cortex of Mecp2-null mice, extrasynaptic NMDA receptor-mediated responses increased markedly. These responses were blocked by memantine, suggesting that extrasynaptic NMDA receptors play an important role in the pathogenesis of RTT. The results suggest that enhancement of postsynaptic GABA<jats:sub>A<\/jats:sub> and extrasynaptic NMDA receptor-mediated responses may underlie impaired somatosensation and that pharmacological blockade of extrasynaptic NMDA receptors may have therapeutic value for RTT. <\/jats:p>","DOI":"10.1152\/jn.00944.2015","type":"journal-article","created":{"date-parts":[[2015,12,17]],"date-time":"2015-12-17T04:38:42Z","timestamp":1450327122000},"page":"1298-1306","source":"Crossref","is-referenced-by-count":21,"title":["Enhancement of postsynaptic GABA<sub>A<\/sub> and extrasynaptic NMDA receptor-mediated responses in the barrel cortex of <i>Mecp2<\/i>-null mice"],"prefix":"10.1152","volume":"115","author":[{"given":"Fu-Sun","family":"Lo","sequence":"first","affiliation":[{"name":"Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary E.","family":"Blue","sequence":"additional","affiliation":[{"name":"Hugo W. 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