Cognitive effects of thalamostriatal degeneration are ameliorated by normalizing striatal cholinergic activity

The loss of neurons in parafascicular thalamus (Pf) and their inputs to dorsomedial striatum (DMS) in Lewy body disease (LBD) and Parkinson's disease dementia (PDD) have been linked to the effects of neuroinflammation. We found that, in rats, these inputs were necessary for both the function of striatal cholinergic interneurons (CINs) and the flexible encoding of the action-outcome (AO) associations necessary for goal-directed action, producing a burst-pause pattern of CIN firing but only during the remapping elicited by a shift in AO contingency. Neuroinflammation in the Pf abolished these changes in CIN activity and goal-directed control after the shift in contingency. However, both effects were rescued by either the peripheral or the intra-DMS administration of selegiline, a monoamine oxidase B inhibitor that we found also enhances adenosine triphosphatase activity in CINs. These findings suggest a potential treatment for the cognitive deficits associated with neuroinflammation affecting the function of the Pf and related structures.

Automated summary

The loss of neurons in the parafascicular thalamus and their inputs to dorsomedial striatum in Lewy body disease and Parkinson's disease dementia have been associated with neuroinflammation. The effects of this neuroinflammation on the function of striatal cholinergic interneurons and the encoding of action-outcome associations necessary for goal-directed action were investigated in rats. The study found that the neuroinflammation inhibited the activity of cholinergic interneurons and disrupted goal-directed control, but these effects could be rescued by administration of selegiline, which enhances the activity of adenosine triphosphatase in cholinergic interneurons.