In contrast to previous post-mortem or fixed tissue histochemical reports, live calcium and mitochondrial imaging data suggest that the enteric nervous system is not generally affected in Parkinson's disease patients.
The spiking activity of the subthalamic nucleus, rather than the activity of striatal projection neurons, orchestrates basal ganglia downstream activity and output commands in health and Parkinson’s disease.
A crucial step during the mitophagy cascade involves the disassembly of connections between mitochondria and the endoplasmic reticulum via the retrotranslocation of Mfn2 tethering complexes by the Parkinson's disease genes PARKIN and PINK1, as well as the ATPase VCP/p97.
The alpha-synuclein fibril structure reported here buries residues 50-57 at the interface between its two protofilaments, suggesting that familial Parkinson's disease associated mutations in these residues lead to a structure not compatible with the one presented here.
When coupling between STN spikes and cortical gamma oscillations was strong, subsequent movement was initiated earlier, independent of changes in mean firing rates, demonstrating the importance of relative spike timing.
LRRK2 G2019S knock-in mice are a genetically faithful model that recapitulates the slow disease progression of familial PD, with initial alterations to behaviour and neurotransmission providing early pathophysiological targets for neuroprotective interventions.