Neuroanatomical phenotyping in the mouse: the dopaminergic system

Voluntary movement in animals is modulated by a number of subcortical systems. One of these resides in the basal nuclei and their associated projections and utilizes dopamine as a neurotransmitter. Apart from regulating movement, the dopaminergic axis is also involved in the control of goal-oriented behavior, cognition, and mood. Disorders of this system result in common human neurologic disorders such as Parkinson's and Huntington's diseases, as well contributing to a host of behavioral conditions, such as schizophrenia, attention deficit hyperactivity disorder, and addiction. Many individual mouse models of human dopaminergic dysfunction have been described in varying degrees of detail. However, when evaluating this region of the brain, the veterinary pathologist is confronted by a paucity of information summarizing the comparative aspects of the anatomy, physiology, and pathology of the central dopaminergic system. In this review, a systematic approach to anatomic phenotyping of the central dopaminergic system in the mouse is described and illustrated using tyrosine hydroxylase immunohistochemistry. Differences between murine neuroanatomy and comparable regions of the nonhuman primate brain are highlighted. Although the mouse is the focus of this review, conditions in domestic animals characterized by lesions within the basal nuclei and its projections are also briefly described. Murine behavioral and motor tests that accompany abnormalities of specific anatomic regions of the dopaminergic axis are summarized. Finally, we review mouse models of Parkinson's and Huntington's diseases, as well as those genetically altered mice that elucidate aspects of dopamine metabolism and receptor function.