Elucidating an anterior cingulate circuit for self-initiated actions and rescue of Parkinsonian akinesia

Abstract

Dopamine (DA) depletion is known to result in Parkinsonian symptoms such as the inability to initiate movements (akinesia). While Parkinsonian akinesia is traditionally associated with reduced DA signaling in the striatum, the contribution of cortical regions that also receive DA projections and project to the striatum remains unclear. Here, we identify a previously unexplored cortical circuit involving D1-like dopamine receptor-expressing neurons in the anterior cingulate cortex (ACC) that is critical for initiating goal-directed movements. We find that a selective activation of ACC-D1+ neurons can flexibly drive targeted movement and locomotion even in akinetic mice after dopamine depletion or receptor antagonism. These findings uncover a cortical mechanism for movement initiation and offer promising new therapeutic targets for treating Parkinsonian akinesia.