Output 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.
-
Output Type
-
Program
-
CRN Team Name
-
Theme
LRRK2 mediates haloperidol-induced changes in indirect pathway striatal projection neurons
PD LRRK2 influences the effects of haloperidol, a common antipsychotic, on striatal indirect pathway neurons. Inhibiting LRRK2 kinase activity reduces haloperidol’s motor side effects, suggesting a way to ease antipsychotic side effects.
Leucine-rich repeat kinase 2 impairs the release sites of Parkinson’s disease vulnerable dopamine axons
Synaptic dysfunctions manifest early in Parkinson's disease. Research on LRRK2 mutations, using advanced genetic models, reveals their effects on neuronal synapses, primarily impacted by the disease, offering insights into potential early therapies.
Dopaminergic axons track somatic signaling in behaving mice
Here, authors used genetic strategies to isolate key dopaminergic neuron subtypes and monitor their axonal and somatic signaling patterns in behaving mice.
Molecular heterogeneity in the substantia nigra: A roadmap for understanding PD motor pathophysiology
This article discusses the existing knowledge of DA neuron subtypes and attempts to provide a roadmap for how their distinctive properties can provide novel insights into the motor symptoms of Parkinson's disease (PD).
Unique functional responses differentially map onto genetic subtypes of dopamine neurons
Genetic strategies to isolate dopaminergic subtypes established a novel subtype of dopamine neurons within the mouse substantia nigra. The results show that the subtypes each display different neural activity patterns related to locomotion and reward
A role for the subthalamic nucleus in aversive learning
The subthalamic nucleus (STN) is critical for behavioral control; its dysregulation consequently correlates with neurological disorders, including PD. To investigate STN and aversion, affective behavior is addressed using optogenetics in mice.
Proportion and distribution of neurotransmitter-defined cell types in the ventral tegmental area and substantia nigra pars compacta
This is the most complete anatomical description of transmitter-defined cell types across SNc and VTA to date. Emphasizing the heterogeneity within these dopamine-rich regions, 57% of SNc neurons express glutamate or GABA markers, as do 78% in VTA.
R1441C and G2019S LRRK2 knockin mice have distinct striatal molecular, physiological, and behavioral alterations
LRRK2 mutations are closely associated with Parkinson’s disease (PD). Convergent evidence suggests that LRRK2 regulates striatal function. Here, by using knock-in mouse lines expressing the two most common LRRK2 pathogenic mutations—G2019S and…
Concerning neuromodulation as treatment of neurological and neuropsychiatric disorder: Insights gained from selective targeting of the subthalamic nucleus, para-subthalamic nucleus and zona incerta in rodents
Neuromodulation, such as deep brain stimulation, is advancing as a clinical intervention in neurological and neuropsychiatric disorders, including Parkinson´s disease. Here, the authors review current literature in the pre-clinical research fields.
Tonic dendritic GABA release by substantia nigra dopaminergic neurons
To characterize the actions of dopamine on substantia nigra pars reticulata (SNr) GABAergic neurons, optogenetic and electrophysiological tools were used in ex vivo mouse brain slices to monitor synaptic transmission arising from neurons.
Molecular and spatial transcriptomic classification of midbrain dopamine neurons and their alterations in a LRRK2G2019S model of Parkinson’s disease
The authors developed an optimized pipeline for single-nucleus RNA sequencing (snRNA-seq) and generated a high-resolution hierarchically organized map revealing 20 molecularly distinct DA neuron subtypes.
Excessive firing of dyskinesia-associated striatal direct pathway neurons is gated by dopamine and excitatory synaptic input
-FosTRAP captures striatal neurons activated in levodopa-induced dyskinesia -Levodopa evokes high firing rates in TRAPed direct pathway striatal neurons (dMSNs) -TRAPed dMSNs show enhanced dopamine sensitivity and excitatory synaptic input
Movement-related increases in subthalamic activity optimize locomotion
We found most neurons in the STN exhibit increased activity during locomotion. Furthermore, optogenetic inhibition of this activity rapidly dysregulated gait. Thus, the STN facilitates movement and may drive locomotor activity in at-risk DA neurons.
Viral overexpression of human alpha-synuclein in mouse substantia nigra dopamine neurons results in hyperdopaminergia but no neurodegeneration
Novel viral vector for α-syn overexpression, AAV-DIO-hASYNWT, can be expressed selectively in neuronal populations based on Cre. Overexpression in DANs did not cause degeneration. AAV-DIO-hASYNWT increased DA levels and locomotor hyperactivity.
