- Countries/Regions
- Sweden
- Category
- Research
- Academic Field
- Medicine
- Related goals of SDGs
| Keyword |
Arc-dVenus transgenic mice, Immediate early gene Arc, whole brain transparency, 3D imaging |
Information on Niigata University
| Name of the professor/researcher |
Toshikuni Sasaoka |
| Position/Faculty |
Professor, Brain Research Institute |
Information on the Counterpart
| Countries/Regions |
Sweden |
| Faculty/Institution |
Experimental Medical Research Basal Ganglia Pathophysiology Unit Dept. of Experimental Medical Science, Lund University |
Detailed Information/Report on Activities
Movement control relies on the interplay of two pathways linking the striatum with the basal ganglia output nuclei. These are the ‘direct pathway’ and the ‘indirect pathway’ originating from striatal projection neurons (SPNs) that express D1 or D2 dopamine receptors, respectively. The loss of dopamine (DA) in Parkinson disease causes hyperactivity of indirect pathway (iSPNs) relative to direct pathway neurons (dSPNs), while an activity imbalance of opposite sign emerges after chronic treatment with L-DOPA inducing dyskinesia (abnormal involuntary movements). In Nilsson’s group, they are combining chemogenetic and pharmacological tools in order to explore the causal contribution of changes in DA receptor stimulation and dSPN/iSPN activity to the hypokinetic and dyskinetic features of Parkinson disease. To this end, they use unilateral 6-OHDA lesions of nigrostriatal DA neurons to produce Parkinson models in rats and mice. In these animal models, they modulate the activity of dSPNs or iSPNs using both excitatory and inhibitory DREADDs, combined with the administration of L-DOPA or specific DA receptor agonists/antagonists. The effects of these interventions are examined using several behavioural and molecular endpoints. The behavioural endpoints include ratings of rodent dyskinesia and dystonia with scales that we have developed and validated. They are studying the causal effects of D1/D2 receptor stimulation, and changes in dSPN/iSPN activity, on specific motor features of Parkinson disease and L-DOPA-induced dyskinesia.
