Given that a key characteristic of individuals with Rett Syndrome is severe cognitive impairment (Rett, 1966; Hagberg et al., 1983; Neul et al., 2010) and the well established role of the cholinergic system in cognitive functions (for review, see Ballinger et al., 2016), we have used the Mecp2 deletion approach to assess the role of MeCP2 in cholinergic neurons and the resulting phenotypes due to its loss. This evidence concerns the gene MECP2 and atypical Rett syndrome.