Dorsomedial striatal neuroinflammation causes excessive goal-directed action control by disrupting astrocyte function
Compulsive actions are typically thought to reflect the dominance of habits over goal-directed action. To investigate this, we mimicked the striatal neuroinflammation that is frequently exhibited in individuals with compulsive disorders in rats, by injecting the endotoxin lipopolysaccharide into the posterior dorsomedial striatum, and assessed the consequences for behavioural control. Surprisingly, this manipulation caused rats to acquire and maintain goal-directed actions under conditions that would otherwise produce habits. Immunohistochemical analyses indicated that these behaviours were a result of astrocytic proliferation. To probe this further, we chemogenetically activated the Gi-pathway in striatal astrocytes, which altered the firing properties of nearby medium spiny neurons and modulated goal-directed action control. Together, results show that striatal neuroinflammation is sufficient to bias action selection toward excessive goal-directed control via dysregulated astrocyte function. If translatable, our findings suggest that, contrary to conventional views, individuals with striatal neuroinflammation might be more prone to maladaptive goal-directed actions than habits, and future interventions should aim to restore appropriate action control.
Authors
- Amolika Dhungana
- Michael D. Kendig
- Karly M. Turner (ORCID: https://orcid.org/0000-0003-3714-5118)
- Laura A Bradfield (ORCID: https://orcid.org/0000-0003-3921-0745)
- Jacqueline A. Iredale (ORCID: https://orcid.org/0000-0002-2733-3177)
- Serena Becchi (ORCID: https://orcid.org/0000-0003-1603-8639)
- Christopher Nolan (ORCID: https://orcid.org/0000-0002-0621-2907)
- Elizabeth E. Manning (ORCID: https://orcid.org/0000-0002-1897-8950)
- Kelly J. Clemens (ORCID: https://orcid.org/0000-0003-2709-218X)
- Hannah R. Drury (ORCID: https://orcid.org/0000-0003-2208-8288)
- Kiruthika Ganesan (ORCID: https://orcid.org/0009-0002-9312-0820)
- Louise Cole (ORCID: https://orcid.org/0000-0001-9206-9272)
- Alessandro Castorina (ORCID: https://orcid.org/0000-0001-7037-759X)
- Arvie Abiero (ORCID: https://orcid.org/0000-0003-1596-6097)
- Joanne M. Gladding (ORCID: https://orcid.org/0000-0002-9616-4258)
- Christopher V. Dayas (ORCID: https://orcid.org/0000-0002-9175-3854)
- Bernard W. Balleine (ORCID: https://orcid.org/0000-0001-8618-7950)
Institutions
- University of Technology Sydney (AU)
- The University of Sydney (AU)
- UNSW Sydney (AU)
- Hunter Medical Research Institute (AU)
- St Vincent's Health (AU)
- Teva Pharmaceuticals (Australia) (AU)
- University of Newcastle Australia (AU)
Publication Details
- Journal
- Neuropsychopharmacology
- Published
- 2025-09-27
- DOI
- https://doi.org/10.1038/s41386-025-02247-4
- Primary Topic
- Neuroendocrine regulation and behavior
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- University of Technology Sydney
- Medical Research Council
- National Health and Medical Research Council