Ventral pallidum efferent pathways via mediodorsal thalamus and lateral habenula mediate distinct aspects of 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 inhibition of the VP projection to lateral
habenula (LHb) confers a learning advantage early during task acquisition.
Conversely, silencing VP projections to mediodorsal thalamus (MD) improves
performance during the late stage of the same task. Downregulation of the
cholinergic VP population improved performance during 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.