Phenotypic disruption to orofacial movement topography in conditional mutants with generalized CamKIIa/Cre D1Tox versus striatal‐specific DARPP‐32/Cre D1Tox ablation of D1 dopamine receptor‐expressing cells

Abstract

Orofacial movements were quantified in (a) DARPP-32/Cre D1Tox mutants, having progressive loss of D1 dopamine receptor expressing striatal medium spiny neurons and (b) CamKIIa/Cre D1Tox mutants, having progressive, generalized loss of forebrain D1 receptor expressing cells. Horizontal jaw movements and tongue protrusions were reduced in DARPP-32/Cre but not in CamKIIa/Cre mutants; head and vibrissae movements were increased in DARPP-32/Cre but decreased in CamKIIa/Cre mutants. In drug challenge studies, tongue protrusions were increased in CamKIIa/Cre mutants following vehicle, suggesting a stress-related phenotype. These findings indicate that mice with progressive loss of striatal-specific D1 receptor expressing cells have an orofacial phenotype that may be modulated by the loss of extrastriatal D1 receptor expressing cells. As progressive loss of D1 dopamine receptor-expressing cells is a hallmark feature of Huntington's disease (HD), these findings may inform the functional role of loss of this cell population in the overall pathobiology of HD.

CREB1 and CREB-binding protein in striatal medium spiny neurons regulate behavioural responses to psychostimulants

“…This is consistent with reports from other studies that have used the DARPP-32 promoter to drive Cre recombinase (Tomiyama et al 2011). Furthermore, as a subpopulation of interneurons within the striatum do not express DARPP-32, 100% deletion would not be expected.…”

Striatal parvalbuminergic neurons are lost in Huntington's disease: implications for dystonia

“…These results must be viewed with caution, however, since ablation of neurons possessing D1 receptors also eliminates D1 receptor-bearing cortical neurons. Thus, it is uncertain if the dystonic phenotype in these mice is attributable to loss of SP+ striatal neurons, or whether loss of cortical D1 neurons accounts for the phenotype 71. In any event, the present findings show that PARV+ striatal interneuron loss is prominent in HD, and available animal data on basal ganglia function are consistent with the view that this loss in motor striatum might contribute to dystonic symptoms.…”

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

“…Regarding spontaneous orofacial movements (Table 1), DARPP-32/Cre D 1 Tox mutants show marked reduction in Jh, reduction in Tg, and increases in Hd and Vb, together with some subtle changes in habituation that are described in detail elsewhere (25). Regarding orofacial movements following drug challenge, DARPP-32/ Cre D 1 Tox mutants show reduction in the effects of SKF 83959 on Jh and Tg, with little change in effects on Jv, CT, Hd, and Vb (25).…”

“…Regarding spontaneous orofacial movements (Table 1), CamKIIa/Cre D 1 Tox mutants show little overall change in Jv, Jh, Tg, and Ct, with decreases in Hd and Vb (25). Regarding orofacial movements following drug challenge, CamKIIa/Cre D 1 Tox mutants show reductions in the effects of SKF 83959 on Tg, Hd, and Vb, with little change in effects on Jv, Jh, and Ct (25).…”