Fig. 8.

Summary diagram of Mef2c haploinsufficiency leading to E/I imbalance and MCHS-like phenotypes that are rescued by NitroSynapsin. Mef2c haploinsufficiency leads to decreased VGAT and increased VGLUT2 protein levels, resulting in E/I imbalance (overexcitability) and synaptic dysfunction. Mef2c haploinsufficiency also causes neuronal loss, notably a reduced number of PV+ inhibitory interneurons. These synaptic and cellular abnormalities are likely the underlying cause of the MCHS-like behavioral phenotypes observed in Mef2c-het mice. The histological and behavioral phenotypes are ameliorated by chronic treatment with NitroSynapsin