The conclusion that emerged from electrophysiological studies in slices as well as in vivo in multiple HD mouse models is that alterations in corticostriatal connections occur in two phases, with increased glutamate release and SPN hyperexcitation at the presymptomatic stage, followed by SPN silencing at the symptomatic stage (Figure 3) (Klapstein et al., 2001; Cepeda et al., 2003; Rebec et al., 2006; Joshi et al., 2009; André et al., 2011b; Miller et al., 2011; Raymond et al., 2011; Indersmitten et al., 2015; Rothe et al., 2015). This evidence concerns the gene SPN and Huntington disease.