The integration of extrinsic and intrinsic neuromodulators in the olfactory system

Abstract

The integration of extrinsic and intrinsic neuromodulators in the olfactory system Kristyn M Lizbinski Neuromodulation is a ubiquitous feature of neural systems, allowing flexible, context specific control over network dynamics by adjusting the biophysical and synaptic properties of neurons. Neuromodulation was first described in invertebrate motor systems and early work established a basic dichotomy for neuromodulation as having either an intrinsic origin (i.e. neurons that participate in network coding) or an extrinsic origin (i.e. neurons from independent networks). Although this dichotomy has been thoroughly considered in motor systems, it has received far less attention in sensory systems. Furthermore, nervous systems are continually subject to a dynamic cocktail of both intrinsic and extrinsic modulators. However, the mechanisms by which single neurons integrate the influence of multiple modulators to alter network function are relatively unexplored. In this dissertation, I discuss the mechanisms by which intrinsic and extrinsic modulators are integrated by single neurons as well as network wide within the context of olfactory processing in the moth Manduca sexta. I begin by discussing the anatomical basis for the integration of two extrinsic modulators, serotonin and dopamine, on principal olfactory neurons. I then discuss the cell-class specific physiological effects of serotonin and dopamine and their distinct effects on olfactory processing. Finally, I discuss the organizing principles and heterogeneity of a diverse group of intrinsic modulatory local interneurons and their potential role in modulating olfactory network dynamics. The heterogeneous nature of neuromodulation is a recurring theme throughout this dissertation as the effects of both intrinsic and extrinsic modulation are generally non-uniform. iii DEDICATION To Mom: You never missed a single soccer game, concert, or academic achievement. Thank you for teaching me the importance of a good sing-along, the healing power of ice cream, and most importantly, your unconditional support and love. To Dad: My original adventure buddy. I love our daily after-work phone calls. Thank you for always believing me even when I didn't believe in myself. I cherish our mountainside chats, and pondering life over a nice glass of wine. To Josh: You're the smartest and most creative person I know. Thanks for being the best brother I could ask for. To Tyler: You're my person, my love, and my best friend. You make me better. Thank you for being my kind of weird, and for your continual love and support. First, I would like to thank my advisor, Andrew Dacks. I am honored to be your first PhD student. You're an amazing scientist and an even better person. You taught me to see the forest through the trees. I have grown so much during my time in your lab thanks to your creative thinking, motivation, and encouragement. Thank you for everything. I could not ask for a better mentor. To my family, I am incredibly lucky to have such a supportive and loving group of people che...