| First Author | Xing H | Year | 2021 |
| Journal | J Cell Physiol | Volume | 236 |
| Issue | 5 | Pages | 3615-3628 |
| PubMed ID | 33169374 | Mgi Jnum | J:365787 |
| Mgi Id | MGI:8188262 | Doi | 10.1002/jcp.30098 |
| Citation | Xing H, et al. (2021) Dual synaptic inhibitions of brainstem neurons by GABA and glycine with impact on Rett syndrome. J Cell Physiol 236(5):3615-3628 |
| abstractText | Rett syndrome (RTT) is a neurodevelopmental disease caused mostly by mutations in the MECP2 gene. People with RTT show breathing dysfunction attributable to the high rate of sudden death. Previous studies have shown that insufficient GABA synaptic inhibition contributes to the breathing abnormalities in mouse models of RTT, while it remains elusive how the glycine system is affected. We found that optogenetic stimulation of GAD-expressing neurons in mice produced GABAergic and glycinergic postsynaptic inhibitions of neurons in the hypoglossal nucleus (XII) and the dorsal motor nucleus of vagus (DMNV). By sequential applications of bicuculline and strychnine, such inhibition appeared approximately 44% GABA(A) ergic and 52% glycinergic in XII neurons, and approximately 49% GABA(A) ergic and 46% glycinergic in DMNV neurons. Miniature inhibitory postsynaptic potentials (mIPSCs) in these neurons were approximately 47% GABA(A) ergic and 49% glycinergic in XII neurons, and approximately 48% versus 50% in DMNV neurons, respectively. Consistent with the data, our single-cell polymerase chain reaction studies indicated that transcripts of GABA(A) receptor gamma2 subunit (GABA(A) Rgamma2) and glycine receptor beta subunit (GlyRbeta) were simultaneously expressed in these cells. In MeCP2(R168X) mice, proportions of GABA(A) ergic and glycinergic mIPSCs became approximately 28% versus 69% in XII neurons, and approximately 31% versus 66% in DMNV cells. In comparison with control mice, the GABA(A) ergic and glycinergic mIPSCs decreased significantly in the XII and DMNV neurons from the MeCP2(R168X) mice, so did the transcripts of GABA(A) Rgamma2 and GlyRbeta. These results suggest that XII and DMNV neurons adopt dual GABA(A) ergic and glycinergic synaptic inhibitions, and with Mecp2 disruption these neurons rely more on glycinergic synaptic inhibition. |
