Biophysical Characterization of Somatosensory Responses in Drosophila Class IV Dendritic Arborization Neurons
Date of Award
Doctor of Philosophy (PhD)
Molecular Biophysics and Biochemistry
Drosophila Class IV neurons are polymodal nociceptors that detect noxious mechanical, thermal, optical, and chemical stimuli. Escape behaviors in response to attacks by parasitoid wasps are dependent on Class IV cells, whose highly branched dendritic arbors form a fine meshwork that is thought to enable detection of the wasp’s needle-like ovipositor barb. To study how mechanical stimuli trigger cellular responses, we developed a novel, tunable, focused 405-nm laser to create highly localized lesions to probe the conditions needed to evoke responses in Class IV neurons. Chapter 2 describes the development of the assay, physical properties of the stimulus, and its likeness to natural stimuli larvae encounter in nature. Next, by imaging calcium signals in dendrites, axons, and soma in response to stimuli of varying positions, intensities, and spatial profiles, we discovered that there are two distinct nociceptive pathways (Chapter 3). Direct stimulation to dendrites (“contact” pathway) produces calcium responses in axons, dendrites, and the cell body, whereas stimulation adjacent to the dendrite produces calcium responses in the axons only (“non-contact” pathway). The “non-contact” axonal pathway displays fast response times, high sensitivity, and is activated with or without direct stimulation of the dendritic arbor. In contrast, the slow, variable, and less sensitive “contact” dendritic pathway is activated only by direct stimulation of dendritic processes. A mathematical model was developed to investigate the origin and magnitude of these cellular calcium responses. Because the axon signals to the central nervous system to trigger escape behaviors, we propose that the density of the dendritic meshwork in Class IV neurons is high not only to enable direct contact with the ovipositor, but also to enable neuronal activation by diffusing signals from damaged surrounding cells via the “non-contact” pathway. On the other hand, studies on dendritic morphology and dendrite tip dynamics suggest that evoked dendritic calcium signals via the “contact” response may facilitate morphological changes to the dendritic arbor following dendritic damage (Chapter 4). Taken together, these in vivo studies provide detailed specifications of somatosensory properties in Class IV dendritic arbors and highlight the ability of compartments in individual Class IV neurons to respond to external stimuli via two distinct activation mechanisms. This ultimately contributes to the body of work on how individual nociceptive neurons integrate inputs and compute outputs.
Basak, Rajshekhar, "Biophysical Characterization of Somatosensory Responses in Drosophila Class IV Dendritic Arborization Neurons" (2021). Yale Graduate School of Arts and Sciences Dissertations. 208.