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Catalog
ASAP is committed to accelerating the pace of discovery and informing a path to a cure for Parkinson’s disease through collaboration, research-enabling resources, and data sharing. We’ve created this catalog to showcase the research outputs and tools developed by ASAP-funded programs.
Article
Impaired dopamine release in Parkinson’s disease
Evidence indicates that impaired dopamine release can result from disruption to a diverse range of Parkinson’s disease-associated genetic and molecular disturbances, and can be considered as a potential pathophysiological hallmark of Parkinson’s disease.
Teams
Article
Early deficits in an in vitro striatal microcircuit model carrying the Parkinson’s GBA-N370S mutation
Published: The results highlight the unique utility of modeling striatal neurons in a modular and highly physiological circuit, which is essential to reveal mechanistic insights of the loss of electrical functional integrity in the striata of GBA1 PD patients. View original preprint.
Teams
Article
Single-cell spatial transcriptomic and translatomic profiling of dopaminergic neurons in health, aging, and disease
Published: The authors used two approaches to ask which genes are expressed during aging in dopaminergic neurons; the cell type affected in Parkinson’s disease. View original preprint.
Teams
Article
Unconventional secretion of α-synuclein mediated by palmitoylated DNAJC5 oligomers
The secretion of endogenous α-syn mediated by DNAJC5 is also found in a human neuroblastoma cell line, SH-SY5Y, differentiated into neurons in the presence of retinoic acid, and in human-induced pluripotent stem cell-derived midbrain dopamine neurons. We propose that DNAJC5 forms a palmitoylated oligomer to accommodate and export α-syn.
Teams
Article
Sst+ GPi output neurons provide direct feedback to key nodes of the basal ganglia and drive behavioral flexibility
Preprint: The GPi-LHb pathway is the main output of the basal ganglia suggested to shape motivated behaviors. Here, the authors propose that GPi Sst+ neurons drive behavioral flexibility through a direct feedback signal to balance the activity of key nodes in the basal ganglia.
Teams
Article
Inhibition of striatal dopamine release by the L-type calcium channel inhibitor isradipine co-varies with risk factors for Parkinson’s
Published: This data show that LTCC function in DA axons, and isradipine effect, are locally governed and suggest they vary in a manner that in turn might impact on, or reflect, the cellular stress that leads to parkinsonian degeneration. View original preprint.
Teams
Article
A fluid-walled microfluidic platform for human neuron microcircuits and directed axotomy
Published: Cortical axons in conduits are severed by a media jet; then, brain-derived neurotrophic factor and striatal neurons in distal chambers promote axon regeneration. As additional conduits and chambers are easily added, this opens up the possibility of mimicking complex neuronal networks and screening drugs for their effects on connectivity. View original preprint.
Teams
Article
An axonal brake on striatal dopamine output by 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.
Teams
Article
Rapid modulation of striatal cholinergic interneurons and dopamine release by satellite astrocytes
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.
Teams
Article
Targeted micro-fiber arrays for measuring and manipulating localized multi-scale neural dynamics over large, deep brain volumes during behavior
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.
Teams
Article
Spatially organized striatum-wide acetylcholine dynamics for the learning and extinction of Pavlovian cues and actions
The used array fiber photometry in mice to investigate how ACh release across the striatum evolves during learning and extinction of Pavlovian associations.
Teams