Dorsomedial striatal neuroinflammation causes excessive goal-directed action control by disrupting astrocyte function
Arvie Rodriguez Abiero, Joanne M. Gladding, Jacqueline A. Iredale, Hannah R. Drury, Elizabeth E. Manning, Christopher V. Dayas, Amolika Dhungana, Kiruthika Ganesan, Karly Turner, Serena Becchi, Michael D. Kendig, Christopher Nolan, Bernard Balleine, Alessandro Castorina, Louise Cole, Kelly J. Clemens & Laura A. Bradfield
Neuropsychopharmacology
September 2025
Abstract
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.