Ventral pallidum efferent pathways via mediodorsal thalamus and lateral habenula mediate default mode network regulation

Transitions between internal and external focus are fundamental to cognition. These shifts depend on the modulation of the default mode network (DMN), of which the ventral pallidum (VP) is a key subcortical node. Here, we examine which VP efferent pathways mediate these transitions, using projection and cell type specific optogenetic silencing. We found that the inhibition of the VP projection to the lateral habenula (LHb) confers a learning advantage early during task acquisition. Conversely, silencing VP projections to the mediodorsal thalamus (MD) improves performance during the late stage of the same task. The downregulation of the cholinergic VP population improved performance at both early and late stages. Thus, silencing these VP outputs promotes escape from a DMN brain state, facilitating attention to external stimuli. Our results confirm a role for VP in DMN regulation and indicate that MD and LHb VP efferent pathways, in concert with cholinergic neuromodulation, mediate different aspects of DMN regulation.