Characterizing the role of two subcortical nuclei in prefrontal regulation of attention

Key Words: Attention, Prefrontal Cortex, Thalamus, Claustrum, Inhibitory Neurons, Circuits, Fiber Photometry, Optogenetics

Attention refers to our ability to filter out irrelevant sensory inputs, like sights, sounds, touch and smell, to effectively process information needed for our current goals. Attention is critical for almost every aspect of our daily life and throughout our development, from the classroom, to the job force, to interpersonal relationships. Despite its importance, we still know very little about the cells and circuits that support its function within the brain. Recent advances in genetic approaches allow us discern the role of specific circuits in behavior enabling researchers to create new circuit maps of the important brain structures involved in attention. We can begin building these maps in the mouse, where our lab has recently developed approaches for assessing attention and other types of cognition while recording from or manipulating activity in circuits of interest.

The prefrontal cortex (PFC) is a brain region that has been identified as a critical hub in attention across species, and is linked to cognitive impairments in several neurodevelopmental disorders. Two major sources of inputs to the PFC have also been linked to attention, the mediodorsal thalamus (MD) and the claustrum. Projections from these regions synapse onto separate neurons and different cortical layers suggesting they play distinct roles in shaping PFC activity during attention. In the proposed studies, we will measure and manipulate activity in these separate projections to PFC in mice while they perform attention assays to determine their roles in attention. Our research will lay the groundwork for future exploration of how activity in these pathways change in mice with genetic mutations found in children with neurodevelopmental disorders with comorbid attention dysfunction. The results from our studies will help us work towards identifying novel circuit biomarkers for attention dysfunction.