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Authors & Affiliations
Epistimi-Anna Makedona, Mu-En Kuo, Pilar Vaca Sánchez, Michael Harvey, Gregor Rainer
Abstract
The Default Mode Network (DMN) is a task-negative network composed of mainly cortical areas with elevated activity during ‘autopilot’ states and decreased activity during goal-directed behavior. Work from our laboratory implicates a basal forebrain node, the ventral pallidum (VP), in the regulation of DMN, suggesting that it dramatically impacts transitions between internally and externally guided behaviors. While VP activation has been shown to positively correlate with DMN upregulation and vice versa, it remains unclear which efferent VP neural pathways mediate these effects. We examine this by optogenetically targeting mediodorsal thalamus (MD), an area which receives robust projections from VP and has been associated with the DMN. We first over trained rats to produce continuous lever presses on a VI-30 schedule, resulting in automatized lever-pressing behavior and serving as a proxy for a DMN-dominated state. We then moved the animals to an auditory discrimination task, requiring them to transition from DMN to externally directed attention. We show that silencing the axonal terminals of VP in MD facilitates the acquisition of the discrimination task in line with previous findings. These results are supported by electrophysiological recordings in the rat. Specifically, we injected AAV-retro-hSyn construct into MD in order to transfect only VP cell bodies with projections to the MD. We then recorded MD activity whilst stimulating the retrogradely transfected VP cell bodies using a neuropixel probe, where robust responses to VP stimulation were recorded. Our results provide insight into the role of the VP-driven activity of MD in task switching DMN-related behaviors.