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Constitutive and conditional mutant mouse models for understanding dopaminergic regulation of orofacial movements:
Katsunori Tomiyama1, John Drago, John L Waddington
1Advanced Research Institute for the Sciences and Humanities, Nihon University, Japan. omiyama@dent.nihon-u.ac.jp
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 D(1-5) dopamine receptors and b) conditional mutations with progressive ablation of D(1) receptor-expressing cells, on the topography of spontaneous and D(1)-like agonist-induced orofacial movements. In constitutive knockouts, D(1) and D(2) exert primary roles in regulating horizontal and vertical jaw movements, respectively, in opposite directions; in contrast, both D(1) and D(2) receptors regulate tongue protrusions and incisor chattering, in the same direction. D(3) and D(5) receptors play more subtle roles in regulating orofacial movements, while D(4) receptors do not play any material role. Progressive loss of forebrain D(1) receptor-expressing cells in CamKIIa/Cre D(1)Tox mutants is associated primarily with decreases in head and vibrissae movements, while progressive loss of striatal D(1) receptor-expressing cells in DARPP-32/Cre D(1)Tox 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.
Insights
Dopamine receptors D(1) and D(2) significantly regulate jaw, tongue, and incisor movements. Progressive D(1) receptor loss impacts head, vibrissae, and jaw movements, offering insights into orofacial disorders.
Area of Science:
- Neuroscience
- Neuropharmacology
- Motor Control
Background:
- Dopamine pathways are crucial for regulating complex motor functions, including orofacial movements.
- Understanding the specific roles of different dopamine receptor subtypes is essential for deciphering motor control mechanisms.
Purpose of the Study:
- To investigate the distinct roles of dopamine receptor subtypes (D1-D5) in regulating spontaneous and agonist-induced orofacial movements.
- To examine the effects of constitutive receptor knockout and conditional ablation of D(1) receptor-expressing cells on orofacial topography.
Main Methods:
- Utilized constitutive knockout mouse models for dopamine receptors D(1) through D(5).
- Employed conditional mutant mouse models (CamKIIa/Cre D(1)Tox and DARPP-32/Cre D(1)Tox) for progressive ablation of D(1) receptor-expressing cells.
- Analyzed spontaneous and D(1)-like agonist-induced orofacial movements.
Main Results:
- D(1) and D(2) receptors differentially regulate jaw movements (horizontal vs. vertical) and similarly control tongue protrusions and incisor chattering.
- D(3) and D(5) receptors have subtle regulatory roles, while D(4) receptors show no significant effect.
- Progressive D(1) receptor loss in forebrain primarily affects head/vibrissae movements, whereas striatal D(1) loss impacts jaw/tongue movements but increases head/vibrissae activity.
Conclusions:
- Dopamine receptors D(1) and D(2) play critical, distinct roles in orofacial motor control.
- Conditional ablation models reveal cell-type-specific functions of D(1) receptors in forebrain and striatum.
- These findings advance understanding of dopaminergic regulation of orofacial movements and potential implications for Parkinson's and Huntington's diseases.
