Probing the mechanisms and circuits underlying orbitofrontal signaling - Project Summary Learning the meaning of cues is necessary for survival. Humans and other animals use this information to learn where and how to acquire food, find mates, or avoid predators. Cues signal many aspects of survival behavior. For example, road signs tell us which way to turn to acquire food (direction), which specific food is offered (e.g., ice cream vs frozen yogurt; outcome identity), as well as whether food is offered at all (value). We are also able to discriminate cues which share the same meaning from their sensory properties (cue identity - e.g., a red octagon and flashing red light both mean stop). The integrated representation of these has been called a “cognitive map”. But how is this kind of information acquired, integrated, and used - what neural circuits underly the formation and use of cognitive maps? The orbitofrontal cortex (OFC) is thought to play a role in forming cognitive maps. However, laboratory assessments of OFC and cognitive maps were conducted in situations where cues, responses, and outcomes were confounded, and not during learning. This leaves open the question of how and why various forms of information are represented in OFC during learning of a complex cognitive operation. This proposal will test the hypothesis that formation of integrated representations in OFC depends on activity in chemosensory, motor, and limbic areas, and OFC ensembles evolve to integrate value-based information. Rats will perform an odor-guided choice task I developed that de-confounds cues, outcomes, and movement, and allows me to assess these during learning. Using cell-type specific neural inhibition, I will first test whether olfactory cortex and limbic areas are necessary for integrating sensory and value information in OFC cognitive maps (Aim 1). I will then test whether the evolution of cognitive maps in OFC depends on value-based information (Aim 2). During the independent phase, I will examine the role of taste and motor association circuits in forming cognitive maps in OFC (Aim 3). I will then record neural activity concurrently in sensorimotor and medial orbitofrontal cortical networks, allowing me to test whether the acquisition of sensorimotor correlates varies with information processing in medial OFC (Aim 4). During the mentored phase, I will receive training critical for my short- and long-term success, including large ensemble recording, computational analyses of high-dimension data, and cell-type specific circuit interference. The proposed training program combines hands-on training with expert experimenters, independent study, formal coursework, and professional scientific meetings. This program will equip me to lead a laboratory focused on circuits, cell-types, cortical networks, neural representations, and how they contribute to learning and the generation of complex behaviors.
