Exploring the Contribution of Distinct mPFC Cell-Types to the Encoding of Decision-Making Outcome

University Of California Los Angeles, Los Angeles CA

Investigators

Abstract

Project Summary / Abstract Cognitive rigidity is the inability to adapt behavior in a context-dependent manner. A hallmark of neurodevelopmental disorders such as autism spectrum disorders and schizophrenia, cognitive rigidity is a debilitating symptom with limited therapeutic tools available for promoting proper cognitive flexibility1,2. Currently, the field’s understanding of the neural mechanisms underlying cognitive flexibility are limited to several implicated brain regions with little insight into the how the microcircuitry of these areas contributes to context-dependent rule switching. Multiple studies point to the medial prefrontal cortex (mPFC) as a critical hub for cognitive flexibility, specifically for its encoding of response and outcome information1,2,3. The proposed work aims to parse apart how information is encoded in different neuron types, how disrupting the activity of these neuronal types impacts context-dependent decision making, and how distinct neurotransmitter signaling onto these cells impacts behavioral flexibility. The overarching goal is to understand the contributions of multiple cell-types in mPFC to the updating of response and outcome task variables in response to changing reward contingencies. Given the advent of genetic tools to target and manipulate genetically-defined neuronal types in mPFC in mice, the goal of this project is to leverage tools such as calcium imaging through cortical microprisms, optogenetic silencing of functionally-distinct neuronal types, and cell-type-specific knockout of key receptors using CRISPR-Cas9 to explore this microcircuitry. I have chosen to pursue this project at UCLA given its vast resources and highly collaborative environment. Furthermore, the Golshani lab is an optimal setting for completing the aims in this proposal due to its long history of using various calcium imaging and optogenetic techniques. With existing access to mentors who are capable in these techniques, as well as the tools themselves, I will quickly proceed through my proposed training plan and become a capable systems neuroscientist. With both the support from experienced lab members as well as the broader UCLA community, I believe that I am well equipped to succeed and that the additional training and resources facilitated by this award will help me to fulfill my goal of becoming an independent career scientist with my own lab at an R1 research university.