Author ORCID Identifier

https://orcid.org/0000-0003-2299-589X

Date of Award

8-8-2023

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience Institute

First Advisor

Dr. Daniel N. Cox

Second Advisor

Dr. Vladimir Bondarenko

Third Advisor

Dr. Charles Derby

Fourth Advisor

Dr. Yaroslav Molkov

Fifth Advisor

Dr. Astrid Prinz

Abstract

We studied cold nociceptive signaling using Drosophila melanogaster that is a powerful model organism providing diverse approaches including genetics, calcium imaging, electrophysiology, animal behavior, and computational modeling. Applying modeling, we investigated mechanisms underlying spiking responses of Drosophila larval Class III (CIII) somatosensory neurons to innocuous and noxious cold temperatures and to rate of temperature decrease. CIII neurons are activated by cold stimuli which mediates a stereotypic cold-evoked behavior, a full-body contraction (CT). This behavioral response is dependent on the speed of temperature change and is potentiated by fast temperature decrease. We identified two basic cold-evoked patterns of CIII neurons: bursting and spiking. In response to a fast temperature drop to noxious cold, CIII neurons distinctly mark different phases of the stimulus. Bursts frequently occurred along with the fast temperature drop, forming a peak of spiking rate and likely coding the high rate of the temperature change. We developed a biophysical model of CIII neurons including key ionic currents that had been implicated in temperature coding. We explain the distinction in occurrence of the two CIII cold-evoked patterns bursting and spiking by dynamics of a thermoTRP current and properties of a voltage gated calcium channel. Transient bursting activity supported by fast TRP current activated by cold temperature and intracellular calcium concentration and inactivated (desensitized) by high levels of the calcium concentration. Transient bursting response is described by type III bursting dynamics, where bursting activity is generated in response to fast change of a stimulus by a system which has silent steady stationary state.

DOI

https://doi.org/10.57709/7XRK-E178

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