Session: 6

PS6-11 | D5 dopamine receptor expression in striatal cholinergic interneurons after nigrostriatal degeneration and L-dopa treatment

Agostina Mónica Stahl


Striatal cholinergic interneurons (SCIN) have been implicated in the motor deficits of Parkinson’s disease (PD) and also in L-dopa-induced dyskinesias.
In previous work, we reported a reduction in a potassium membrane current containing Kv1.3 subunits that mediates SCIN hyperexcitability in a mouse model of PD. L-dopa treatment not only did not revert this effect, but instead turned SCIN even more excitable and further reduced Kv1.3 current. This was not due to a decrease in cell surface localization of Kv1.3.
SCIN express D5 dopamine receptors (D5R) that modulate Kv1.3 SCIN currents and may mediate the hyperexcitability produced by L-dopa treatment. As these effects persist after L-dopa has worn off and D5R stimulation ceases, we propose that increased ligand-independent activity (L-IA) of D5R contributes to negative regulation of Kv1.3 in dyskinetic mice.
As increased L-IA can derive from increased expression of D5R, here we address whether D5R are differentially expressed in SCIN from control, parkinsonian and dyskinetic mice. For this, we performed immunohistochemistry labeling of D5R in brain sections from mice that express a red fluorescent protein in all cholinergic neurons and acquired images from the dorsolateral striatum. Preliminary results from the quantification of D5R label in SCIN somata show higher D5R levels in dyskinetic than parkinsonian mice. These results suggest that targeting D5R in SCIN could provide new anti-dyskinetic therapies.