Author ORCID Identifier
Year of Publication
Doctor of Philosophy (PhD)
Arts and Sciences
Dr. Robin Lewis Cooper
Understanding the role of various chemical messengers in altering behaviors and physiological processes is a common goal for scientists across multiple disciplines. The main focus of this dissertation is on characterizing the action of an important neurotransmitter, acetylcholine (ACh), modulating larval Drosophila melanogaster neural circuits and heart. In this dissertation, I provide important insights into the mechanisms by which ACh influences the formation and performance of select neural circuits, while also revealing significant details regarding its role in additional physiological functions, including cardiac pace making. In Chapter 1, I provide a general overview of ACh action in mammals and flies with a particular focus on the physiological and behavioral effects of cholinergic signaling in the context of modulation of neural circuits and developmental impacts.
Chapters 2 and 3 are dedicated to the role of ACh in modulating larval Drosophila heart rate (HR). Previous analysis has been performed identifying neuromodulator influence on larval heart rate, and I add to the current understanding of chemical modulation of cardiac function utilizing a pharmacological approach to assess ACh regulation of HR. I provide evidence that ACh modulates larval HR primarily through muscarinic receptors. I follow this by employing an optogenetic approach to assess ACh and additional neuroendocrine modulation of HR in an intact system in Chapter 3, further illuminating ACh regulation of larval HR.
Chapter 4 is dedicated to describing the role of ACh in modulation of neural circuits underlying larval locomotion, feeding behavior, and sensorimotor circuit activity. I discuss the pharmacological approach taken to address this topic. Here, behavioral as well as electrophysiological approaches reveal a contribution from both ACh receptor subtypes in regulation of these behaviors. I leverage this information and describe the influence of a specific receptor subtype, the muscarinic acetylcholine receptor (mAChR) on the function of these circuits by using combined pharmacological and genetic approaches to strengthen the pharmacological assessment, discussed in Chapter 8.
An additional goal of this work is to refine the optogenetic technique in the larval Drosophila model. Chapter 5 discusses useful experimental paradigms that allow for investigation of repetitively activating light-sensitive opsins on neuronal physiology in the larval model. Chapter 6 discusses an intriguing, previously undefined identification of Glutamic acid decarboxylase1 expression in larval body wall muscle, which was identified using optogenetic approaches in concert with electrophysiology. Furthermore, I combine these approaches to discuss the development of an experimental paradigm to address the developmental impacts of altering sensory (cholinergic) input on the formation and maintenance of a specific mechanosensory circuit (Chapter 8). Chapter 7 discusses the implication of deep tissue injury on proprioceptive sensory function in two model proprioceptive organs in crab and crayfish.
Digital Object Identifier (DOI)
Malloy, Cole A., "PROFILING THE ACTION OF ACETYLCHOLINE IN THE DROSOPHILA MELANOGASTER LARVAL MODEL: HEART, BEHAVIOR, AND THE DEVELOPMENT AND MAINTENANCE OF SENSORIMOTOR CIRCUITS" (2017). Theses and Dissertations--Biology. 47.