Striatal cholinergic interneurons and astrocytes lose cilia and show dysregulation of Hedgehog signaling in mice with a Parkinson's disease-associated, G2019S LRRK2 mutation or upon loss of PPM1H phosphatase specific for LRRK2-phosphorylated Rab GTPases.
Acetylcholine, released from cholinergic fibers originating from the medial septum, shapes social memory, and controls the CA2 hippocampal circuit via nicotinic receptors localized on GABAergic interneurons.
Cocaine elicits opposing activity changes in D1R vs D2R spiny projection neurons of the nucleus accumbens with much variability, subsequent recruitment of a subset of D1R neurons drives behavioral sensitization.
RNAseq and ATACseq are utilized to identify transcription factors participating in striatal compartmentation into striosome and matrix, and roles for Stat1, Olig2, and Foxf2 are validated in vitro and in vivo.
In vivo dopamine neuron imaging-based neuroprotective small molecule screen in larval zebrafish and mechanistic investigation using conditional CRISPR knockout and cell-type-specific RNA-seq analysis, coupled with cross-species analyses including human clinical data interrogation, uncover potential disease-modifying therapeutics for Parkinson's disease (PD).
Promoting a Warburg-like shift in astrocytic metabolism through reduced mitochondrial electron transport accommodates the energetic burden caused by brain trauma without overwhelming cellular respiration and redox to salvage dopaminergic neurons.