Work

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

Year: 2025

Type: article

Abstract: 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.

Source: iScience

DOI: 10.1016/j.isci.2025.113885

Authors: Epistimi-Anna Makedona, Mu-En Kuo, Michael Harvey, Gregor Rainer

Institution: University of Fribourg

Language: English

Topic: Memory and Neural Mechanisms

Subfield: Cognitive Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,240