The goal of the proposed research is to understand how perceptual decision-making circuits in the prefrontal cortex (PFC) compare distinct streams of sensory information to select actions. A large body of work identifies the PFC as an important node in perceptual decision-making circuits, with a critical role in sensory representation and action selection. However, how the PFC uses sensory signals to generation choice signals is unclear. Previous work from our laboratory has shown that the anterior cingulate cortex (ACC), a sub-region of PFC, plays an important role in visually guided decision-making behavior. Furthermore, work from our lab and others find that the visual cortex (VC) projects directly to the ACC, and that the hemispheres of the ACC are heavily interconnected. Our recent work shows that these inputs convey information to each hemisphere of the ACC about its contralateral and ipsilateral visual hemifield. Thus, these pathways provide an opportunity to examine how distinct streams of sensory information are used to generate perceptual choice signals in the prefrontal cortex. I have designed a two-alternative forced choice task that requires the comparison of convergent information across visual hemifields. Head-fixed mice are trained on a two-alternative forced choice task that requires them to compare visual cues in either hemifield and report the location of a target cue by rotating a ball. I hypothesize that the ACC integrates VC and ACC inputs to guide action selection in this behavior. I also propose that this comparison process is reflected in the activity of the ACC?s sensory representation, evidence, and choice cells. To evaluate these hypotheses, I will combine this sophisticated head-fixed behavior with areal and projection-specific optogenetics and in vivo multiphoton imaging.
In Aim 1, I will determine the contributions of VC and ACC to this behavior using areal optogenetics. I will also test the hypothesis that axons from VC and ACC convey distinct information about either visual hemifield by using projection-specific optogenetics.
In Aim 2, I will use two-photon imaging and population decoding to identify sensory representation, evidence, and choice cells in the ACC of behaving mice. Then, I will combine axonal inactivation with two-photon imaging during behavior to determine how the information these two pathways convey interacts with sensory representation, evidence, and choice cells. Together, these experiments will determine the role of distinct inputs to visual decision-making in the ACC and identify a local visual perceptual decision-making circuit. The prevalence of executive dysfunctions in numerous brain disorders and scarcity of targeted therapeutics to treat them urges basic research on the brain mechanisms underlying higher cognitive functions like decision-making. By identifying the contributions of long-range and local PFC circuits to decision- making, these studies may highlight critical targets for the development of novel treatments.
Every day, we make countless decisions; when this ability is impaired, as it is in numerous brain disorders, the impact on daily life can be severe. The proposed research aims to broaden our understanding of how local circuits in the prefrontal cortex coordinate distinct streams of information to guide decision-making in mice, where tools for causal interrogation are available. Successful completion of the experiments described in this proposal will broaden our knowledge of the neural mechanisms underlying cognitive functions and may identify specific circuit targets for treatments of depression, attention deficit disorder, and schizophrenia.
