Work

Mutant huntingtin expression in somatostatin-positive interneurons contributes to neurophysiological and behavioral phenotypes in BACHD mice

Year: 2026

Type: article

Abstract: Huntington's disease (HD) is caused by expansion of the polyglutamine stretch in the widely expressed huntingtin (HTT) protein. Patients with HD have motor, psychiatric and cognitive changes due to changes in a variety of neural circuits. Somatostatin-expressing interneurons (SST-INs) can regulate neural circuits largely by inhibiting their target cells. Behaviorally, brain-wide inhibition of SST-INs increased anxiety in mice. Silencing striatal SST-INs caused a decrease in movement in the open field. Mutant HTT (mHTT)-expressing mice exhibited abnormal motor, cognitive and psychiatric-like changes, as well as electrophysiological changes in a variety of neurons, including striatal SST-INs. However, it is unknown whether cell-autonomous expression of mHTT in SST-INs contributes to HD-associated behavioral phenotypes or causes abnormal electrophysiological changes in striatal SST-INs. To address these questions, we reduced mHTT expression in SST-INs throughout the brain of BACHD mice. Our findings show that brain-wide reduction of mHTT in SST-INs rescues anxiety-like behavior in male BACHD mice in the light-dark box, without improving performance in the open field or on the rotarod. Additionally, expression of mHTT in striatal SST-INs cell autonomously drives their increased excitability.

Source: Disease Models & Mechanisms

DOI: 10.1242/dmm.052513

Authors: Jahmel A. Fowler, Mariangela Scarduzio, Cayla Pool, Casey D. Mahan, Michelle Gray

Institutions: University of Alabama at Birmingham, UAB Medicine, Xavier University of Louisiana

Language: English

Topic: Genetic Neurodegenerative Diseases

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,750