The Deep Focus: Subcortical Networks Mediating Sustained Attention

Objective

To effectively interact with our environment, the brain must filter out vast amounts of irrelevant information. This process is known as selective attention. Although the circuits that mediate selective attention have been extensively studied, little is known about how the brain sustains attention over time. In my previous work, I used volumetric functional ultrasound imaging (vfUSI) to examine the mouse brain while it performed tasks that probe sustained attention. Unexpectedly, one of the areas that showed the strongest modulation was the midbrain reticular nucleus (MRN), which is part of the ascending reticular activating system (ARAS). Evidence from fMRI and lesion studies in humans implicates the ARAS in maintaining wakefulness, arousal, attention, and consciousness. However, limitations in spatial resolution and inter-individual variability have hindered the precise anatomical and functional characterization of this system, which spans several midbrain and brainstem regions. Building on these findings, in this project I will study Attention With an Active Reticular Engagement (AWARE), focusing on the MRN, a central but yet poorly understood component of the ARAS. First, I will map the input and output connectivity of the MRN in mice to establish its anatomical framework. Second, I will use cell-type-specific manipulations to investigate the MRN's functional contributions, particularly to the intermediodorsal thalamus and reuniens, during a visually guided spatial attention task. Finally, I will use two-photon calcium imaging with GRIN lenses to investigate whether and how distinct MRN subpopulations modulate attentional states. These experiments will provide fundamental insights into how the brain sustains attentional focus, an essential cognitive function disrupted in many psychiatric and neurodegenerative disorders.