Constitutive and Conditional Mutant Mouse Models for Understanding Dopaminergic Regulation of Orofacial Movements: Emerging Insights and Challenges

Abstract

Among numerous mechanisms implicated in the regulation of orofacial movements, dopamine-containing neurons have received the most extensive study. Here we review the effects of a) constitutive knockout of D1–5 dopamine receptors and b) conditional mutations with progressive ablation of D1 receptor–expressing cells, on the topography of spontaneous and D1-like agonist–induced orofacial movements. In constitutive knockouts, D1 and D2 exert primary roles in regulating horizontal and vertical jaw movements, respectively, in opposite directions; in contrast, both D1 and D2 receptors regulate tongue protrusions and incisor chattering, in the same direction. D3 and D5 receptors play more subtle roles in regulating orofacial movements, while D4 receptors do not play any material role. Progressive loss of forebrain D1 receptor–expressing cells in CamKIIa/Cre D1Tox mutants is associated primarily with decreases in head and vibrissae movements, while progressive loss of striatal D1 receptor–expressing cells in DARPP-32/Cre D1Tox mutants is associated primarily with reductions in jaw movements and tongue protrusions but increases in head and vibrissae movements. Further application of constitutive and particularly conditional mutants may clarify further not only dopaminergic regulation of orofacial movements but also the pathophysiology of orofacial dysfunction in Huntington’s disease and Parkinson’s disease. Keywords:: dopamine D1–5 receptors, orofacial movement, constitutive knockout, conditional mutant, D1 receptor–expressing cell