Reduced GABAergic synaptic transmission in the nucleus tractus solitarius in Mecp2‐null mice (1130.20)

Abstract

Rett syndrome (RTT), a devastating neurodevelopmental disorder, is caused by loss‐of‐function mutations in the X‐linked methyl‐CpG binding protein 2 (Mecp2) gene. Respiratory dysfunction is one of the major clinical features, presumably due to defective GABAergic function because enhancing GABAergic transmission improved the respiratory phenotype and prolonged survival in RTT mice. We test the hypothesis that deficiency in Mecp2 gene reduces GABAergic signal transmission in the NTS where respiratory information is first received and integrated. Spontaneous inhibitory postsynaptic currents (sIPSCs) and miniature IPSCs (mIPSCs) were recorded from NTS neurons in brainstem slices obtained from age‐matched male Mecp2‐null mice and wild‐type littermates. Compared to those from wild‐type mice (n = 11 neurons), NTS neurons from Mecp2‐null mice (n = 12 neurons) had a left‐ward shift in cumulative probability of sIPSC amplitudes (p < 0.05) without significant changes in inter‐event intervals (p > 0.05). Similarly, there was a significant left‐ward shift in mIPSC cumulative probability of amplitudes (p < 0.05) but not inter‐event intervals (p > 0.05). The data are consistent with the hypothesis and suggest that reduced GABAergic signaling via post‐synaptic mechanism(s) in the NTS contributes to respiratory dysfunction in RTT.Grant Funding Source: supported by: 1R01 HD064817, International Rett Syndrome Foundation