Summary
This project investigates a novel cortical cause of dystonia following preterm birth, focusing on the role of sensorimotor cortex parvalbumin-positive interneurons (PVINs) and their interaction with striatal cholinergic interneurons (ChINs).
Cortical dystonia of prematurity
US · IL
NIH
grant
awarded
#nih-1R01NS140701-01A1
What they want
The project aims to address gaps in understanding, predicting, and treating dystonia in cerebral palsy by exploring a cortical origin. It hypothesizes that sensorimotor cortex PVIN inhibition causes dystonia after preterm birth via striatal ChIN excitation. The research will leverage a novel mouse model of preterm birth and quantitative dystonia measures to determine if cortical dysfunction precedes dystonia (Aim 1), if PVIN inhibition excites ChINs (Aim 2), and if PVIN excitation can reduce dystonia (Aim 3). These studies will establish the critical role of sensorimotor PVINs in dystonia prediction, pathophysiology, and treatment, providing a foundation for future translational studies.
Deliverables
- Establish the critical role of sensorimotor PVINs in dystonia prediction
- Establish the critical role of sensorimotor PVINs in dystonia pathophysiology
- Establish the critical role of sensorimotor PVINs in dystonia treatment
- Provide foundation for future translational studies testing cortically-targeted treatments for dystonia following preterm birth
Technical requirements
- Novel mouse model of preterm birth demonstrating dystonia by postnatal day 42
- Quantitative dystonia measures in mice (clinically validated)
- Longitudinal assessment of sensorimotor PVIN number
- Cortical oscillatory activity assessment using electroencephalography (EEG)
- Dystonic behavior assessment
- Fiber photometry
- Chemogenetic inhibition of sensorimotor PVINs
- Chemogenetic inhibition of corticostriatal neurons
- Chemogenetic excitation of sensorimotor PVINs
