Studies in genetic rodent models of HD have demonstrated that expression of mutant huntingtin and progressive dysfunction of frontal-subcortical networks induces complex changes at the cellular and systems levels including decreases in glutamatergic corticostriatal transmission and synchronous MSN burst firing, aberrant synaptic plasticity, and increases in intrinsic membrane excitability of MSNs and a subpopulation of GABAergic interneurons (Cepeda et al., 2007; Bunner and Rebec, 2016; Puigdellivol et al., 2016; Raymond, 2017; Holley et al., 2019). This evidence concerns the gene HTT and Huntington disease.