ORCID

0000-0003-1464-0001

Date of Award

4-22-2024

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Neurosciences)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Frontal cortex supports sophisticated behaviors by controlling phylogenetically older subcortical brain regions. Within the deep layers of cortex, subcortically projecting pyramidal neurons integrate local and long-range inputs along the entire depth of the cortical column. How subcortically projecting neurons might be fractionated into cell types and how their unique features constrain top-down communication is unknown. In this dissertation, I first established the output circuit architecture of subcortically projecting neurons in rat orbitofrontal cortex at a cellular resolution. I found that subcortically projecting neurons preferentially innervated a single target, demonstrating a one-neuron-one-target projection logic. Such target-defined projection neurons were molecularly distinct and spatially segregated into previously unappreciated, intermediate sublayers of L5b. These anatomical results suggest that subcortically projecting neurons represent connectivity defined cell types which are positioned to act as specialized information channels. To test the functional roles of OFC subcortical projections, I next developed two task variants that enable testing for (1) static and dynamic learning rate representations by manipulating the outcome distribution and (2) subjective value representations that could drive dopaminergic signaling and in turn, momentary choice preferences. Taken together, this work reveals the higher-order organizational principles of rat orbitofrontal cortex, namely a “one neuron one target” projection logic and a “deeper farther” spatial logic. Such a highly structured circuit architecture bolters the hypothesis that subcortically projecting neurons might serve as the final arbiters, routing critical information that can drive both healthy and maladaptive behaviors.

Language

English (en)

Chair and Committee

Adam Kepecs

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