Date of Award

5-2-2022

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience Institute

First Advisor

Daniel N. Cox

Second Advisor

Michael J. Galko

Third Advisor

Angela M. Mabb

Fourth Advisor

Javier Stern

Abstract

Metazoans detect and differentiate between innocuous (non-painful) and/or noxious (harmful) environmental cues using primary sensory neurons, which serve as the first node in a neural network that computes stimulus specific behaviors to either navigate away from injury-causing conditions or to perform protective behaviors that mitigate extensive injury. The ability of an animal to detect and respond to various sensory stimuli depends upon molecular diversity in the primary sensors and the underlying neural circuitry responsible for the relevant behavioral action selection. Elucidating molecular and circuit bases of sensory discrimination and integration in animals with simple body plans and relatively small nervous systems (e.g. Drosophila) have the potential to reveal generalizable principles of how underlying neural connectivity allows for selective information processing at different scales from molecular to neural network levels for coordinating behavioral response(s). Recent studies in Drosophila larvae reveal somatosensory class III multidendritic (CIII md) neurons function as multimodal sensors regulating distinct behavioral responses to innocuous mechanical and nociceptive thermal stimuli. Molecular bases underlying CIII md neuron mediated modality-specific behavioral responses and circuit bases of cold nociceptive behaviors remain incompletely understood. 1. Functional analyses indicate that multimodal behavioral output is dependent upon CIII md neuron activation levels with stimulus-evoked Ca2+ displaying relatively low vs. high intracellular levels in response to gentle touch vs. noxious cold, respectively. Our analyses support novel, modality-specific roles for metabotropic GABAergic signaling and Ca2+ induced Ca2+ release (CICR) mechanisms in regulating intracellular Ca2+ levels and cold evoked behavioral output from multimodal CIII neurons. 2. Recent advances in circuit bases of behavior have identified and functionally validated Drosophila larval somatosensory circuitry involved in innocuous (mechanical) and noxious (heat and mechanical) cues. However, central processing of cold nociceptive cues remained unexplored. We implicate multisensory integrators, premotor and projection neurons functioning downstream of CIII md neurons that are required for cold evoked behavioral responses. Collectively, we demonstrate how Drosophila larvae process distinct stimuli using multimodal neurons and highlight functional diversity of somatosensory circuitry for generating stimulus specific behaviors.

DOI

https://doi.org/10.57709/28894314

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