Neuroinflammation in the dorsomedial striatum causes excessive goal-directed action control by disrupting homeostatic astrocyte function

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 and examining the behavioural outcomes. We found that neuroinflammation in the dorsomedial striatum of rats caused them to be excessively goal-directed, as they acquired and maintained goal-directed actions under conditions that would otherwise produce habits. Immunohistochemical analyses suggested that these behaviours were a result of astrocytic proliferation. To investigate 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 cause excessive goal-directed control through dysregulated astrocyte function. Our findings suggest that individuals with striatal neuroinflammation are more prone to excessive goal-directed actions than habits, and that future interventions should aim to restore appropriate goal-directed control.