Dr Laura Bradfield (UTS)

Abstract

Neuroinflammation has been observed in the striatum and hippocampus of individuals with psychiatric disorders and neurodegenerative diseases to different extents, but whether this causes the behavioural disturbances experienced by such individuals or is simply another symptom of their disease is unknown. In our lab we have begun to piece together causal evidence from studies in rats and mice that neuroinflammation in the dorsal striatum, ventral striatum, and dorsal hippocampus alters goal-directed action and choice behaviours in a region-specific manner. Specifically, we injected the endotoxin lipopolysaccharide in each region to induce neuroinflammation in separate cohorts of animals and then tested them on a range of behavioural assays. Rats with dorsomedial striatal neuroinflammation demonstrated aberrant intact goal-directed control in a range of conditions under which control animals did not, such as when fed a high-fat high-protein home chow, or after training that otherwise induced habits. By contrast, ventral striatal neuroinflammation abolished goal-directed action control. In dorsal hippocampus, neuroinflammation produced an acceleration of goal-directed action control in females and a facilitation of Pavlovian approach behaviour in male mice. Immunohistochemical analyses linked the expression of astrocytes but not microglia in the striatum to changes in behaviour, whereas both microglia and astrocyte expression in dorsal hippocampus were associated with behavioural changes. Consistent with these findings, chemogenetically altering the activity of astrocytes in both striatal regions abolished goal-directed action control, whereas this was only partially true for the dorsal hippocampus. Evidence from cell culture experiments confirmed that the activation of both microglia and astrocytes caused neuronal excitation in hippocampal neurons. Together, these results reveal that region-specific differences in neural-glial interactions that result from neuroinflammation lead to different profiles of choice behaviour in a manner that could give insight into the mechanisms underlying psychiatric diseases and neurodegenerative disorders.