OLFACTORY CORTICAL CONTROL DEFINES STRIATAL SENSORY REPRESENTATIONS By KATE A. WHITE A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 2018 1 © 2018 Kate A. White 2 ACKNOWLEDGMENTS First and foremost, I would like to thank my family and friends for their unyielding support. To my mother and father: your sacrifices have enabled me to follow my dreams, and it is my sincerest hope that I can one day repay you for all that you’ve done for me. Thank you for all the big and little things you do. To my brother, Dan: thanks for giving me the courage to follow my dreams and push me out of my comfort zone. To my grandfathers: thank you so much for your support and belief in me. To all my wonderful friends who have supported me despite my random absences from their lives, in particular, Sam, Ashli, Rachel, Jessi, Steph, and Sam: thank you so much for your long- distance support that kept me grounded throughout this process. To my undergraduate mentors: Dr. G Andrew Mickley, who inspired my passion for science with his kind patience and true interest in my ideas and dreams. You gave me the tools and confidence to succeed where I thought I could not. To Dr. Christopher Turner, who sat with me on weekends, early in the morning, and late in the evening to help me with my undergraduate thesis – you are no longer here, but you left a deep impact on me, even if we only knew one another for a short time. Thank you for teaching me persistence and to expand my scientific horizons. To my lab mates, past and present: there are too many to name, but special thanks to the following: Sean Copley and Jamie LocPort from the Willis lab, you both made my transition into graduate school a wonderfully warm and welcome one, and I am deeply lucky to call you friends. To Dr. Marie Gadziola, who had the heavy task to teach me just about everything in the Wesson lab: thank you so much for your patience, thoughtfulness, and kindness. To Dr. Luke Stetzik, for being the best lab-roommate 3 during my time at the University of Florida: you seem to always know what to say, and I sincerely appreciate the guidance you gave me. To Kaitlin Carlson: short acknowledgement words are totally insufficient to thank you, but: I am deeply grateful to have been able to go through graduate school with such a fun, kind, passionate, and hilarious labmate. From struggling together, laughing together, traveling to conferences together, and being moth-lights together: thank you, so much, for being the best labmate, roommate, and friend I could have ever asked for. To my committees, past and present: Dr. Roy Ritzmann, Dr. Hillel Chiel, Dr. Brian McDermott, and Dr. Mark Willis from Case Western Reserve University, who gave me indispensable guidance in my early stages. To my current committee: Dr. Daniel Wesson, Dr. Jeff Martens, Dr. Steve Munger, Dr. Gonzalo Torres, and Dr. Barry Setlow, for being willing to pick up where the other committee left off and giving me fresh and crucial insights into my project. Thank you all so much for shaping my mind as a young scientist. To my collaborators: Dr. Minghong Ma and Dr. Fuqiang Xu, thank you and your labs so much for your support, assistance, and hard work. Lastly, and importantly, to my husband, Tony White: you’re the only reason I have been able to work so hard for as long as I have, and this PhD is yours just as much as it is mine. You supported me when I felt like I could not achieve my goals, and stepped up when I was swamped with grading and writing and experiments. You somehow managed to accept the fact that I needed to move away for the last year of my graduate training. You drove with me from Cleveland to Gainesville and tried to make this difficult situation somehow fun. Thank you for being by my side through this 4 process – your support has meant more than you will ever know, and I am so excited to show you that this hard work has been worthwhile. 5 TABLE OF CONTENTS page ACKNOWLEDGMENTS .................................................................................................. 3 LIST OF TABLES ............................................................................................................ 8 LIST OF FIGURES .......................................................................................................... 9 LIST OF ABBREVIATIONS ........................................................................................... 10 ABSTRACT ................................................................................................................... 11 CHAPTER 1 INTRODUCTION .................................................................................................... 13 Importance of Sensory Information Processing ...................................................... 13 Odor Processing Within Early Olfactory Structures ................................................ 15 Olfactory Bulb Dynamics During Odor Information Processing ............................... 16 The PCX and its Association Fiber System ............................................................ 19 The Role of the OT as an Olfactory and Striatal Structure ...................................... 28 Focus of Dissertation Research .............................................................................. 31 2 A CORTICAL PATHWAY MODULATES SENSORY INPUT INTO THE OLFACTORY STRIATUM1 ..................................................................................... 35 Preface ................................................................................................................... 35 Materials and Methods............................................................................................ 37 Animals............................................................................................................. 37 Stereotaxic Surgery and Viral Injections ........................................................... 38 Behavior and Stimulus Presentation ................................................................ 39 Optical Probe Fabrication ................................................................................. 40 In Vivo Electrophysiology and Optical Stimulation ............................................ 41 In Vitro Electrophysiology and Optical Stimulation ........................................... 41 Histology ........................................................................................................... 43 Data Analysis ................................................................................................... 45 Results .................................................................................................................... 45 Viral Strategy for the Optogenetic Control of PCX Principal Neurons .............. 45 Activation of PCX Neurons Enhances OT Activity ............................................ 47 Activation of PCX Association Fibers Within the OT Modulates OT Activity ..... 49 Activation of PCX Association Fibers Bidirectionally Modulates the Representation of Odors in the OT ............................................................... 50 PCX Principal Neurons Synapse with, and Evoke Monosynaptic Responses Within, OT D1- and D2-Type MSNs2 ............................................................. 53 Topographical Organization of PCX Neurons Innervating OT D1- and D2- Type MSNs3 .................................................................................................. 54 6 Discussion .............................................................................................................. 56 Contributions ........................................................................................................... 62 3 SUMMARY AND CONCLUSIONS .......................................................................... 78 Future Directions for Dissecting Secondary Olfactory System Connectivity ........... 79 Cellular Origins and Terminations of Secondary Structure Connections .......... 80 Neural Consequences of PCX Association Fiber Perturbation ......................... 82 Behavioral and Perceptual Roles for the PCX-OT Connection......................... 87 Caveats and Considerations ............................................................................ 92 PCX and OT as Components of a Cortico-Striatal Loop ......................................... 95 Role of Recurrent Circuitry in PCX and OT Odor Representations ......................... 99 LIST OF REFERENCES ............................................................................................. 104 BIOGRAPHICAL SKETCH .......................................................................................... 122 7 LIST OF TABLES Table page 2-1 Number of mice used for in vivo experiments......................................................62 8 LIST OF FIGURES Figure page 1-1 Simplified map of sensory information processing in the brain............................33 1-2 Schematic of higher-order olfactory structures in the rodent brain......................34 2-1 Olfactory fixed-interval task..................................................................................63 2-2 Histological confirmation of electrode/fiber optic implantation sites for in vivo recordings.................................................................................................64 2-3 Viral strategy for the optogenetic control of PCX principal neurons.....................65