Loss of CREB-dependent pro-survival gene expression after extrasynaptic NMDAR activation seems to precede cell death and neurodegeneration in diseases like Alzheimer’s disease (AD) and Huntington’s disease (HD) (Shankar et al., 2007; Milnerwood et al., 2010; Malinow, 2012; Kessels et al., 2013; Papouin and Oliet, 2014; Parsons and Raymond, 2014; Wild et al., 2015; Carvajal et al., 2016; Bading, 2017; Grochowska et al., 2017; Marcello et al., 2018; Parra-Damas and Saura, 2019). This evidence concerns the gene CREB1 and Huntington disease.