University of Texas at El Paso ScholarWorks@UTEP Open Access Theses & Dissertations 2019-01-01 Shining Light On An Amygdala -- Brainstem Connection Important For Attention Processing Jose Carlos Cano University of Texas at El Paso Follow this and additional works at: https://digitalcommons.utep.edu/open_etd Part of the Biology Commons, and the Neuroscience and Neurobiology Commons Recommended Citation Cano, Jose Carlos, "Shining Light On An Amygdala -- Brainstem Connection Important For Attention Processing" (2019). Open Access Theses & Dissertations. 2835. https://digitalcommons.utep.edu/open_etd/2835 This is brought to you for free and open access by ScholarWorks@UTEP. It has been accepted for inclusion in Open Access Theses & Dissertations by an authorized administrator of ScholarWorks@UTEP. For more information, please contact [email protected]. SHINING LIGHT ON AN AMYGDALA – BRAINSTEM CONNECTION IMPORTANT FOR ATTENTION PROCESSING JOSE CARLOS CANO Doctoral Program in Biosciences APPROVED: Michael Kenney, Ph.D., Chair Karine Fenelon, Ph.D., Co-chair Arshad M. Khan, Ph.D. Anita Quintana, Ph.D. Edward Castaneda, Ph.D. Stephen Crites, Ph.D. Dean of the Graduate School Copyright © by Jose Carlos Cano 2019 Dedication To the immaculate quintessence of maternal sacrifice, unwavering strength, devout perseverance, and infinite love (B. R.). To the bright muse ravaging with daily beautiful light the uncertainty of the future (O. S.). Dedicatoria A la inmaculada quintaesencia del sacrificio materno, la fuerza inquebrantable, la perseverancia devota y el amor infinito (B. R.). A la brillante musa que asola con hermosa luz diaria la incertidumbre del futuro (O. S.). SHINING LIGHT ON AN AMYGDALA – BRAINSTEM CONNECTION IMPORTANT FOR ATTENTION PROCESSING by JOSE CARLOS CANO, B.S. DISSERTATION Presented to the Faculty of the Graduate School of The University of Texas at El Paso in Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY Department of Biological Sciences THE UNIVERSITY OF TEXAS AT EL PASO December 2019 Acknowledgements There are three key people that guided me through the divine comedy of my Ph.D. odyssey. First, I cannot express the immense gratitude, respect and admiration I have for Dr. Joanne T. Ellzey, who gave me the opportunity and privilege to work in her Analytical Cytology Core Facility and to be in charge of her precious Zeiss EM-10. In there, I was constantly amazed by the unmatched magnificence and delicacy of electron microscopy. I greatly treasure Dr. Ellzey and Dr. Lawrence Ellzey, and their continuous support and motivation to pursue a Ph.D. degree. Dr. Arshad Khan, the embodiment of all mad scientists in cartoons and video games (except for the evil intentions). The motivation, ambition, joy and ideas that Dr. Khan emits in every conversation is mind-blowing, to the point that I picture myself picking pieces of my brain from the wall and floor after every conversation. I want to thank Dr. Khan for introducing me to Neuroscience, for the constant support, for the scientific input, and for being an unparalleled role model at UTEP. Then, to complete the Triforce was the young, driven, innovative and enthusiastic Dr. Karine Fenelon. I want to thank Dr. Fenelon for the opportunity to work under her mentorship, for always setting an example, for inviting me to Amherst to continue working on my research project, for helping my professional and scientific development, and for providing me with a unique opportunity to continue my career. I especially want to thank Dr. Michael Kenney for taking over the time-consuming mentor responsibilities, for his experienced insight and for co-sponsoring the NIH grant! I want to thank my committee: Dr. Edward Castaneda, Dr. Anita Quintana and Dr. Kristin Gosselink (former advocate and author of extremely helpful committee meeting notes!) for their incredible support and scientific contribution. I greatly appreciate the of support v from Dr. Giulio Francia, Dr. Manuel Llano, Dr. Gosselink; and the support and input of Dr. Joseph A. Gogos and Dr. Amy MacDermott from Columbia University. I want to thank my comrades in research for sharing the joy and pain at UTEP: fellow “guinea pig” Andy (a.k.a. Sebastian), the always driven and intense L. Patricia, the fer-1 enthusiast V. Ines, the pokemon-master Eddie, the holiday enforcer Mireya, and Carla Loyola; the present labmates at UMass Amherst: Dr. Wan Yun Huang (and her never-ending questions that have made me a better mentor), Ernie, Erika, Bryan, Ethan and Brittany; Dr. Ellen Walker for the confocal microscopy mentoring, Ken Negishi for the mapping and Illustrator tutoring. I also want to commend the patch-clamp recording ‘deities’ for allowing me, after an initial frustrating semester, to ‘break the seal’ and achieve whole-cell recordings. This journey would have been overwhelming without the support and love of my incredible family. I want to thank: Bertha Rodriguez, my mother and co-owner of this degree, for her unconditional love, sacrifice and prayers; my sister Susana for always being there to help me and discipline me to be better; my sister Vero for her mice drawings and graphic design skills, companionship, and along with my brother Omar and my nephew Jose Pablo, for the relaxing, yet thrilling and much-needed, video game Sundays; to all the “zarigüeyas” (Sofia, Mariana, Isabella, Valeria and Angel) for the joy you create with a single glance or a funny face. I want to thank Olga B. Soto for being my shelter in the many times of desperation, for always asking the questions I never thought of, and for the unwavering love and support through time and distance. vi Abstract We are continuously being exposed to an exorbitant amount of sensory information, which should result overwhelming. However, the nervous system operates several intrinsic sensory filtering mechanisms that allow us to cope with such sensory cluttering and shape appropriate behavior. Sensorimotor gating is a pre-attentive neuronal filtering mechanism that gates superfluous sensory information, and orients attentional resources towards salient information processing. Its relevance becomes in individuals suffering from schizophrenia and several otherwise unrelated neuropsychiatric disorders where sensorimotor gating is impaired. To understand the neural impaired mechanisms, extensive research studies have focused on first identifying the neural substrates underlying sensorimotor gating. This doctoral research project focuses on a connection, centrally located in the sensorimotor gating circuit, for its potential role in pre-attentive processing. In mice, we first characterized the neuroanatomy and neurochemistry of a connection from the central nucleus of the amygdala (CeA) to the caudal pontine reticular nucleus (PnC), at the core of the sensorimotor gating circuit. Secondly, we analyzed the synaptic properties of an excitatory subset of CeA-PnC synapses, and whether it modulates PnC activity in vitro. We then assessed the role of this connection in sensorimotor gating in vivo. Lastly, to provide a mechanistic basis for the role of this excitatory connection in an inhibitory mechanism, we investigated the identity of the PnC components receiving CeA excitatory inputs. Results from this dissertation research project contribute to the knowledge of the neural substrates underlying sensorimotor gating. Ultimately, a better insight on this matter might reveal potential therapeutic targets to be tested in models of diseases associated with sensorimotor gating deficits. vii Table of Contents Acknowledgements ......................................................................................................... v Abstract .......................................................................................................................... vii Table of Contents .......................................................................................................... viii List of Tables .................................................................................................................. xii List of Figures ................................................................................................................ xiii Abbreviations ................................................................................................................. xv Prologue ......................................................................................................................... xx Chapter 1: Introduction .................................................................................................... 1 1.1 Sensorimotor gating ...................................................................... .................. 1 1.1.2 The relevance of sensorimotor gating .................................. .................. 2 1.2 The startle reflex ............................................................................ .................. 4 1.2.1 Neural basis of the acoustic startle reflex ............................. .................. 6 1.2.2 Plasticity of the startle reflex: a tool to evaluate sensory information processing .................................................................................... ................ 10 1.2.2.1 Habituation and sensitization ............................................ ................ 10 1.3 Prepulse inhibition: the gold standard of sensorimotor gating ........ ................ 13 1.3.1 The prepulse inhibition of the acoustic startle reflex paradigm .............. 14 1.3.2 A clinical and