Collaborative Research Network Archive

Preprint: The striatum is required for normal action selection, movement, and sensorimotor learning. Here, the authors assess how striatal ensembles are formed and how their dynamics may evolve throughout motor learning.

Preprint: Mutations in genes that regulate mitophagy, a key mitochondrial quality control pathway, are causative for neurological disorders including Parkinson’s. Here, the authors identify a novel stress response pathway activated by mitochondrial damage that regulates mitophagy in neurons.

Published: The authors designed a new micro-fiber array approach capable of chronically measuring and optogenetically manipulating local dynamics across over 100 targeted locations simultaneously in head-fixed and freely moving mice, enabling the investigation of cell-type and neurotransmitter-specific signals over arbitrary 3D volumes at a spatial resolution and coverage previously inaccessible.

Preprint: Astrocytes are increasingly thought to have underestimated important roles in modulating neuronal circuits. Astrocytes in the striatum can regulate dopamine transmission by governing the extracellular tone of axonal neuromodulators. The authors reveal that striatal astrocytes occupy a cell type-specific anatomical and functional relationship with cholinergic interneurons.

Preprint: Depolarization of distal axons is necessary for neurons to translate somatic action potentials into neurotransmitter release. Studies have shown that striatal cholinergic interneurons can drive ectopic action potentials in dopamine (DA) axons and trigger DA release. The authors show that this action occurs within a broader context of axonal signal integration.

The integrated stress response (ISR) is a conserved biochemical pathway that regulates protein synthesis. As such, the ISR is implicated in a wide range of diseases, including brain disorders. In this review, the authors consider the ISR's contribution to brain disorders through the lens of its potential effects on synaptic plasticity.

Preprint: The intricate process of α-synuclein aggregation and fibrillization hold pivotal roles in Parkinson’s disease (PD). While mouse α-synuclein can fibrillate in vitro, whether these fibrils can reproduce structures in the human brain remains unknown. Here the authors report the first atomic structure of mouse α-synuclein fibrils.

Preprint: Recent advances have expanded the role of lipid droplets (LDs) beyond passive lipid storage, implicating their involvement in metabolic processes. Neuronal LDs have been identified in several neural structures, raising questions about their contribution to neurodegenerative disorders. This study outlines an improved methodology to stimulate and isolate mature LDs.

Preprint: The data presented here demonstrates that neurons and their nerve terminals can make use of LDs during electrical activity to provide metabolic support when glucose is in short supply.

Preprint: Based on genetic studies, lysosome dysfunction is thought to play a pathogenetic role in Parkinson’s disease (PD). Here, the authors show that VPS13C, a bridge-like lipid transport protein and a PD gene, is a sensor of lysosome stress/damage.

Preprint: Decreased excitability of pyramidal tract neurons in layer 5B (PT5B) of primary motor cortex (M1) has recently been shown in a dopamine-depleted mouse model of parkinsonism. The authors hypothesized that decreased PT5B neuron excitability would disrupt firing patterns of neurons in layer 5 of primary motor cortex.

Preprint: Neurodegenerative disorders have overlapping symptoms and high comorbidity rates, but this is not reflected in overlaps of risk genes. The authors investigated whether ligand-receptor interactions (LRIs) are a mechanism by which distinct genes associated with disease risk can impact overlapping outcomes.