Student Theses and Dissertations

Author

Adele Bubnys

Date of Award

2019

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

Pfaff Laboratory

Abstract

Generalized arousal (GA) is a fundamental force in the nervous system that alerts an individual to abrupt changes in its environment. A state of high GA is operationally defined by increases in an animal’s a.) locomotor output, b.) responsiveness to sensory stimuli, and c.) emotional reactivity. Previous studies have identified the nucleus gigantocellularis (NGC), a small group of large-bodied neurons in the hindbrain reticular formation, as a potential neuronal substrate for GA. These neurons are responsive to a wide range of sensory modalities and have diverse projections that target both forebrain areas and motor effectors directly within the spinal cord, thereby facilitating rapid responses to sensory stimulation. Here, we used three different approaches to study the role of GA in driving and modulating mammalian motor activity: in silico modeling of GA circuits, in vitro culture of a reticulospinal circuit, and in vivo behavioral assays of circadian transitions in GA. In our in silico study, we constructed a variety of computational models of the generalized arousal circuit and asked how modifying specific aspects of the NGC and its connectivity would influence the responsiveness of motor effectors in the circuit to arousing sensory stimuli. These models reveal that an NGC with a homogeneous microstructure that integrates all inputs equally and bifurcating projections that simultaneously target limbic and spinal areas is most effective at transducing an arousing sensory signal.

Comments

A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy

Available for download on Wednesday, June 03, 2020

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