# Advancement and Application of a Novel Basal Ganglia Thalamocortical Circuitry Model in Dystonia Rats

> **NIH VA I01** · VA VETERANS ADMINISTRATION HOSPITAL · 2020 · —

## Abstract

Dystonia is a devastating condition characterized by ineffective, twisting movements and contorted
postures. While surgical treatments are effective for those with many genetic or undetermined
causes, treatments for secondary forms due to such as trauma, strokes and cerebral palsy are poorly
responsive to current medical and surgical therapies. Because of the high incidence of dystonia from
head trauma, our soldiers are particularly susceptible to developing secondary dystonia. Despite its
impact on human health, the underlying abnormalities in the brain had not prior to our recent studies
been well investigated in animal models.
 Our investigations in rodent models of dystonia are revealing remarkable insight into how
abnormal signals originating in the basal ganglia, located in a deep region of the brain, are causing
another deep brain region, the thalamus, to send abnormal signals onto the motor cortex at the
surface of the brain. The abnormal brains signals thus generated in the motor cortex ultimately lead
to erroneous signals being sent to the muscles, causing the devastating motor features of this
condition. We discovered that the neuronal (brain cell) activity in a specific part of the basal ganglia,
the globus pallidus externa (GPe) was grossly silent in rodents with experiment dystonia from being
jaundiced in their brain. This led us to pursue destructive chemical lesions in GPe in other rodents to
further test if silencing the GPe would indeed produce dystonia. After affirming this, we developed a
second much improved focused rodent model which will be invaluable for our ongoing studies.
 In the new studies, we will utilize a modern technique, which takes advantage of the properties
of opsins, which are light-sensitive proteins contained in microorganisms, including bacteria. Opsins,
like the light receptors in the human eye, are important for producing actions in these
microorganisms, such as movement, in response to light. By incorporating viral-opsin constructs
directly into select brain cells and then passing a light probe through the brain near these cells,
different colored light frequencies can be used to stimulate or inhibit the ‘infected’ brain cells with very
high precision. These opsins will be used here to program the abnormal brain cell activity in
previously defined pathological brain regions, including in different nuclei (regions) of the basal
ganglia and the thalamus. Our intent is to program the brain cells in these regions to approach more
natural patterned activity, with the hope of reversing the dystonia in the rodents. Additional methods
will involve introducing a pharmacological agent into the thalamus to turn off electrical burst
properties of these brain cells to determine the role of bursting of these brain cells in programming of
normal and pathological movement. Brain cells in the thalamus exist in two states: a tonic firing mode
and a burst firing mode and the importance of each has been debated. Our studie...

## Key facts

- **NIH application ID:** 9827482
- **Project number:** 5I01BX001147-06
- **Recipient organization:** VA VETERANS ADMINISTRATION HOSPITAL
- **Principal Investigator:** Mark S Baron
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2011-04-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9827482

## Citation

> US National Institutes of Health, RePORTER application 9827482, Advancement and Application of a Novel Basal Ganglia Thalamocortical Circuitry Model in Dystonia Rats (5I01BX001147-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9827482. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*