Dorsomedial striatal neuroinflammation causes excessive goal-directed action control by disrupting homeostatic astrocyte function

Abstract

Compulsive actions have been confusingly described as reflecting both excessive habitual and excessive goal-directed action control. Here we sought to resolve this contradiction by inducing the neuropathology commonly observed in individuals with compulsive disorders, specifically by causing neuroinflammation in the dorsomedial striatum of rats. We found that this caused rats to be excessively goal-directed, acquiring and maintaining goal-directed actions under conditions that would otherwise produce habits. Immunohistochemical findings suggested that these behaviours were a result of astrocytic proliferation and its effects on neuronal activation. We therefore investigated the role of striatal astrocytes specifically, demonstrating that chemogenetically activating the Gi-pathway in astrocytes altered the firing properties of nearby medium spiny neurons and modulated goal-directed action control. Together, results suggest that striatal neuroinflammation is sufficient to cause excessive goal-directed action control through the dysregulation of astrocyte function suggesting that individuals with striatal neuroinflammation are excessively goal-directed rather than habitual, information that could be used to direct future interventions and/or treatments.