Alexandra Nelson
University of California-San Francisco, CA·Neuroscience
Dopamine-related drugs can be essential treatments, but they can also cause troubling movement and behavior problems. Parkinson's disease (PD) is treated with dopamine replacement drugs, such as levodopa or dopamine agonists that mimic dopamine.
- Fields
Neuroscience
Medicine & Clinical Research
Pharmacology
- Topics
Parkinson's disease
levodopa-induced dyskinesia
impulse control disorder
- Grants
- 3 known grants, through Mar 2031
What they work on
- Test whether local inhibitory synapses within the striatum, and inhibitory inputs from the globus pallidus, are altered in and contribute to levodopa-induced dyskinesia, using in vivo and ex vivo electrophysiology, optogenetics, and chemogenetics in parkinsonian mice.
- Explore striatal mechanisms of impulse control disorder using a mouse model that pairs a delay-discounting task with the dopamine agonist pramipexole.
- Determine whether D2 or D3 dopamine receptors in specific cell types are required for haloperidol-induced tardive dyskinesia, using targeted genetic deletion in mice.
- Link individual dyskinetic mouth movements to striatal dopamine release and neuron activity, using the dLight sensor, photometry, electrophysiology, optogenetics, and a head-mounted camera with automated behavior detection.
- Determine how dynorphin, a neuropeptide made by direct-pathway striatal neurons, and prefrontal cortex inputs to the dorsomedial striatum shape behavioral flexibility and impulse control in mouse models of Parkinson's disease.
- Identify neuronal ensemble activity patterns of disrupted executive function in parkinsonian mice using in vivo 2-photon imaging and single-unit electrophysiology.
More about the research
These drugs can trigger involuntary movements and impulse control disorder (ICD). ICD shows up as compulsive gambling, shopping, or eating. Antipsychotic drugs that block dopamine can cause tardive dyskinesia, which brings lasting involuntary mouth movements. The lab studies the striatum, a deep brain region that dopamine controls. It asks how the striatum's cells and connections produce these side effects and the thinking problems of PD. Across three projects it uses mouse models with recordings, imaging, and genetic tools that turn cells on or off.
Why it matters
People with Parkinson's disease often face involuntary movements, compulsive behaviors, and thinking problems that current dopamine drugs do not fix, or even cause. People taking antipsychotics for schizophrenia or bipolar disorder can develop tardive dyskinesia, which is often permanent. Learning which brain cells and synapses drive these problems could point to treatments that keep dopamine's benefits without these complications.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Jun Wang
Texas A&M University-College Station, TX·Neuroscience
Define how cocaine-strengthened inhibition from dMSNs onto cholinergic interneurons reduces thalamic excitation of these interneurons and acetylcholine release, using dual-channel optogenetics, electrophysiology and genetically encoded ACh sensors.
Mark D Bevan
Northwestern University, IL·Neuroscience
Determine how basal ganglia indirect-pathway activity and movement stay normal in presymptomatic MitoPark mice despite ongoing loss of dopamine neurons, using electrophysiology, imaging and behavior.
Eduardo Gallo
Fordham University, NY·Neuroscience
Test whether dopamine D2 receptors on cholinergic interneurons of the nucleus accumbens control impulsive choice, by using cell type-specific genetic tools in mice to both increase and decrease receptor levels and measuring performance on a delay discounting task.
The school
University of California-San Francisco: 89 labs on PI Pages, $2.1B a year on research, 164 research doctorates a year.
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