Related Experiment Video
Updated: Nov 29, 2025

Studying Pre-formed Fibril Induced α-Synuclein Accumulation in Primary Embryonic Mouse Midbrain Dopamine Neurons
Published on: August 16, 2020
α-Synuclein Aggregates Increase the Conductance of Substantia Nigra Dopamine Neurons, an Effect Partly Reversed by
E Hill1, R Gowers2,3, M J E Richardson2
1School of Life Sciences, University of Warwick, Coventry CV4 7AL, United Kingdoms.
Abstract:
Dopaminergic neurons (DNs) in the substantia nigra pars compacta (SNpc) form an important part of the basal ganglia circuitry, playing key roles in movement initiation and coordination. A hallmark of Parkinson's disease (PD) is the degeneration of these SNpc DNs leading to akinesia, bradykinesia and tremor. There is gathering evidence that oligomeric α-synuclein (α-syn) is one of the major pathologic species in PD, with its deposition in Lewy bodies (LBs) closely correlated with disease progression. However, the precise mechanisms underlying the effects of oligomeric α-syn on DN function have yet to be fully defined. Here, we have combined electrophysiological recording and detailed analysis to characterize the time-dependent effects of α-syn aggregates (consisting of oligomers and possibly small fibrils) on the properties of SNpc DNs. The introduction of α-syn aggregates into single DNs via the patch electrode significantly reduced both the input resistance and the firing rate without changing the membrane potential. These effects occurred after 8-16 min of dialysis but did not occur with the monomeric form of α-syn. The effects of α-syn aggregates could be significantly reduced by preincubation with the ATP-sensitive K+ channel (KATP) inhibitor glibenclamide. These data suggest that accumulation of α-syn aggregates in DNs may chronically activate KATP channels leading to a significant loss of excitability and dopamine release.
Related Concept Videos
Parkinson's Disease: Treatment
Parkinson's Disease is primarily a result of the loss of dopaminergic neurons in the substantia nigra pars compacta. The cornerstone of...
Drugs Affecting Neurotransmitter Synthesis
Drugs Affecting Neurotransmitter Release or Uptake
Neural Regulation
Parkinson's Disease: Overview
Ligand-Gated Ion Channel Receptor: Gating Mechanism

