TY  - INPR
A1  - Kovacheva, Lora
A1  - Shin, Josef
A1  - Farassat, Navid
A1  - Roeper, Jochen
T1  - Kv4.3 channel downregulation mediates chronic post-lesional pacemaker acceleration in surviving dopamine substantia nigra neurons
T2  - bioRxiv
N2  - Substantia nigra dopamine (SN DA) neurons are progressively lost in Parkinson disease (PD). While the molecular and cellular mechanisms of their differential vulnerability and degeneration have been extensively studied, we still know very little about potential functional adaptations of those SN DA neurons that – at least for some time – manage to survive during earlier stages of PD. We utilized a partial lesion 6-OHDA mouse model to characterize initial electrophysiological impairments and chronic adaptations of surviving identified SN DA neurons, both in vivo and in vitro. Early after lesion (3 weeks), we detected a selective loss of in vivo burst firing in surviving SN DA neurons, which was accompanied by in vitro pacemaker instability. In contrast, late after lesion (>2 months), in vivo firing properties of surviving SN DA neurons had recovered in the presence of 2-fold accelerated pacemaking in vitro. Finally, we show that this chronic cell-autonomous adaptation in surviving SN DA neurons was mediated by Kv4.3 channel downregulation. Our study demonstrates substantial homeostatic plasticity of surviving SN DA neurons after a single-hit non-progressive lesion, which might contribute to the phenotype of initially surviving SN DA neurons in PD.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/72918
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-729183
IS  - 2021.08.09.455657
ER  -