Vikram Shakkottai
University of Texas Southwestern Medical Center, TX·Neuroscience
Smooth, coordinated movement depends on the cerebellum, a brain region that fine-tunes motion. The cerebellum relies on input from the inferior olive, a small cluster of neurons in the brainstem.
- Fields
Neuroscience
Physiology
Medicine & Clinical Research
- Topics
inferior olive
inferior olivary nucleus
hypertrophic olivary degeneration
- Grants
- 1 known grant, through May 2029
What they work on
- Define how membrane excitability, meaning how easily a neuron fires, relates to inferior olive degeneration in SCA1 knockin mice. Test whether restoring normal excitability prevents the degeneration.
- Separate intrinsic (within the neuron) from extrinsic (incoming synaptic) contributions to olive dysfunction in SCA1 mouse models, building on in vivo electrophysiological recordings.
- Determine why enlarged olive neurons in SCA1 become more excitable, focusing on loss of function in potassium (K+) channels, which normally dampen neuron firing.
More about the research
When inferior olive neurons degenerate, people can develop tremor and ataxia, a loss of movement coordination. These neurons can die for two kinds of reasons. Some die from internal molecular damage, as in spinocerebellar ataxias, a family of inherited movement disorders. Others die after losing the calming, inhibitory input they normally receive from the cerebellum, a condition called hypertrophic olivary degeneration (HOD). The two causes are usually thought to kill cells in different ways. This project tests whether they actually share a common mechanism.
Why it matters
Degeneration of the inferior olive underlies tremor and ataxia, including in spinocerebellar ataxias. The project is expected to show whether too much electrical excitability is a shared cause of olive neuron death. If it is, lowering neuron excitability could become a treatment approach to protect these neurons and preserve movement control. This approach might also apply to other neuron loss caused by excessive excitatory input.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Sharan Srinivasan
University of Michigan, MI·Neuroscience·Early-career
Test whether exercise improves motor behavior in spinocerebellar ataxia mouse models by correcting abnormal Purkinje neuron firing or through other pathways, using electrophysiology and motor testing.
Indira M Raman
Northwestern University, IL·Neuroscience
Determine how the synchrony of inhibitory input from many Purkinje neurons shapes the firing of cerebellar nuclei neurons, using in vitro synaptic studies in mice and larval zebrafish.
Adam Avery
Oakland University, MI·Neuroscience
Define the neuronal interactomes, the full sets of binding partners, of normal and SCA5-mutant L253P β-III-spectrin in Drosophila neurons, using immunoprecipitation coupled to mass spectrometry.
The school
University of Texas Southwestern Medical Center: 40 labs on PI Pages, $869M a year on research, 86 research doctorates a year.
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