Jochen Roeper - Pacemaker mechanism and plasticity of DA SN neurons

ViDA 2021 - Thur June 24th 2021
Jochen Roeper
Neurophysiology Goethe University Frankfurt
Pacemaker mechanism and plasticity of DA SN neurons
The mechanisms of pacemaking in dopamine neurons in the substantia nigra (DA SN) are still not clear and particular the role of L-type channels are both controversial and potentially relevant in the context of neuroprotection in Parkinson Disease. Using a mouse model where only Cav1.3 channels are sensitive to the dihydropyridine isradipine we defined the functional role of this low-threshold L-type channel to autonomous pacing in vitro. Dynamic clamp in vitro experiments revealed how Cav1.3 channels also boost high-frequency discharge in the in vivo burst frequnency range of lateral SN DA neurons. Clinically relevant concentrations of isradipine in the low nanomolar range are tested in this setting and compared to systemic effects of isradipine on in vivo firing properties of identified DA SN neurons. Our results demonstated how lateral SN DA neurons can be targeted selectively in vivo. Finally, we identified the acceleration of pacemaker function in DA SN neurons surviving in a partial 6-OHDA lesion model via downregulation of Kv4.3 channels. We demonstrate that DA SN pacing can be targeted in vivo by dihydropyridines and also adapts in surviving neurons after a lesion.