Behavioral and neurophysiological correlates of striatal dopamine depletion: A rodent model of Parkinson's disease

Both limb and cranial motor functions are adversely impacted by Parkinson's disease (PD). While current pharmacological and surgical interventions are effective in alleviating general limb motor symptoms of PD, they have failed to provide significant benefit for cranial motor functions. This suggests that the neuropathologies mediating limb and cranial motor impairments in PD may differ. Animal models provide a mechanism by which the potential neural dysfunctions underlying these different motor impairments may be characterized. Central goals to our laboratory have been to (a) determine the differential responses of cranial motor and limb motor function to striatal dopamine depletion and (b) determine the differential effects of striatal dopamine depletion on the integrity of cranial motor and limb motor neural circuits. This paper details the use of a comprehensive battery of limb and cranial motor behavioral tasks and the application of intracortical microstimulation to assess corticospinal and corticobulbar circuits in a rodent model of PD. Our work suggests that striatal dopamine depletion does differentially affect cranial and limb motor function and corticospinal and corticobulbar circuits. Further, we propose that cranial motor impairments in PD may be mediated by pathology both within and outside nigrostriatal dopamine system.Learning outcomes: Readers will be able to (a) describe a set of motor tests used to assess limb motor and cranial motor function in an animal model of Parkinson's disease, (b) understand the application of intracortical microstimulation to assess corticospinal and corticobulbar circuits, (c) describe the differential effects of dopamine depletion on limb motor and cranial motor function in a rodent model of PD, and (d) understand the potential role of dysfunction outside the nigrostriatal system mediating cranial motor impairments in Parkinson's disease.

► In this article we reviewclinical profiles of individuals with Parkinson's disease and highlight recent research from our laboratory documenting disparate improvements in cranial motor vs. limb motor dysfunction in a group of PD patients.
► We outline the use of rodent animal models of PD as a mechanism for studying the underlying neural mechanisms underlying cranial motor and limb motor dysfunction in PD. We delineate the use of well-established behavioral tests to assay limb motor and cranial motor dysfunction in dopamine depleted animal models.
► We review the use of intracorticalmicrostimulation as a means for assessing the integrity of corticobulbar and corticospinal circuits in a rodent model of Parkinson's disease.