A Perceptual-Mnemonic Role for the Perirhinal Cortex in Age-Associated Cogntive Decline
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A perceptual-mnemonic role for the perirhinal cortex in age-associated cogntive decline Item Type text; Electronic Dissertation Authors Burke, Sara Nicole Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 05/10/2021 10:52:58 Link to Item http://hdl.handle.net/10150/195350 1 A PERCEPTUAL-MNEMONIC ROLE FOR THE PERIRHINAL CORTEX IN AGE-ASSOCIATED COGNITIVE DECLINE by Sara Nicole Burke _____________________ A Dissertation Submitted to the Faculty of the GRADUATE INTERDISCIPLINARY PROGRAM IN NEUROSCIENCE In Partial Fulfillment of the Requirements For the Degree of DOCTOR OF PHILOSOPHY In the Graduate College THE UNIVERSITY OF ARIZONA 2 0 0 9 2 THE UNIVERSITY OF ARIZONA GRADUATE COLLEGE As members of the Dissertation Committee, we certify that we have read the dissertation prepared by Sara Nicole Burke entitled A perceptual-mnemonic role for the perirhinal cortex in age-associated cognitive decline and recommend that it be accepted as fulfilling the dissertation requirement for the Degree of Doctor of Philosophy _______________________________________________________________________ Date: 4/17/09 Carol A. Barnes _______________________________________________________________________ Date: 4/17/09 Lynn Nadel _______________________________________________________________________ Date: 4/17/09 Lee Ryan _______________________________________________________________________ Date: 4/17/09 Rebecca D. Burwell Final approval and acceptance of this dissertation is contingent upon the candidate’s submission of the final copies of the dissertation to the Graduate College. I hereby certify that I have read this dissertation prepared under my direction and recommend that it be accepted as fulfilling the dissertation requirement. ________________________________________________ Date: 4/17/09 Dissertation Director: Carol A. Barnes 3 STATEMENT BY AUTHOR This dissertation has been submitted in partial fulfillment of requirements for an advanced degree at the University of Arizona and is deposited in the University Library to be made available to borrowers under rules of the Library. Brief quotations from this dissertation are allowable without special permission, provided that accurate acknowledgment of source is made. Requests for permission for extended quotation from or reproduction of this manuscript in whole or in part may be granted by the head of the major department or the Dean of the Graduate College when in his or her judgment the proposed use of the material is in the interests of scholarship. In all other instances, however, permission must be obtained from the author. SIGNED: Sara Nicole Burke 4 ACKNOWLEDGEMENTS “To get through the hardest journey we need to take only one step at a time, but we must keep on stepping” (Chinese proverb). I would like to thank all of you that encouraged and helped me to keep stepping, without you this process would have been much less enjoyable and perhaps impossible. To my graduate student cohort: Marsha Penner, Lisa Marriott-Roko, Stephen Cowen, Alex Thome, Zaneta Navratilova, and Lan Hoang, you helped to stimulate my creativity through provoking discussions, informal journal clubs, and company during happy hour. Many of you were also my shoulders to cry on and my partners in crime when I needed either one. To the other students and post docs at NSMA both past and present: Monica Chawla, David Eusten, Nathan Insel, Peter Lipa, James Lister, Kaori Nishiuchi, Ephron Rosenzweig, and Vicki Sutherland, I have learned something from, or been inspired by, each of you. This dissertation work would not have been completed without the help of the amazing undergraduate and high school students I had the pleasure of mentoring: Ajay Uprety, Saman Nematollahi, Jenelle Wallace, and Ellen Wann. You dedicated countless hours to helping me spin tetrodes, collect data and cut clusters when I was travelling, training monkeys, or getting married. You also shared with me an enthusiasm for science that helped to keep me energized. I look forward with a great keenness to what the future holds for each of you. Administrative and technical support is at times thankless, but more often it is priceless. Thank you to Kim Bohne for the hyperdrive construction, Joseph Bohanick for data collection and always being good in an emergency, Jie Wang for cutting a heroic amount of clusters, Michael Montgomery for saving the day each time I had a computer or data meltdown, and to Michelle Carroll, Luann Snyder, and Erin Wolfe for your superb organizational skills and always tolerating my fear of paperwork. I have reflected many times on how fortunate I was to conduct my dissertation research with Carol A. Barnes. Your contributions to the field of the neurobiology of aging are immeasurable. You have taught me by example to think big, push myself, and the power of diplomacy. You also always knew when to rein me in and make me focus. I look forward to more years of science under your wisdom. Last, but certainly not least, I owe a great thanks to my phenomenal husband Andrew P. Maurer. To me, you have been a teacher, a sounding board, a database of the literature, a collaborator, an inspiration, and most importantly my best friend. You pushed me to challenge myself but also reminded me to slow down every once in a while. Thank you for going home to feed the dogs when I could not, and always knowing where my keys and cell phone are located. The best part of graduate school was finding you and I look forward to watching ourselves grow old together. Hopefully, you will still be able to tell me where my keys are when we are 70! 5 DEDICATION This dissertation is dedicated to my family. You have always supported me and believed that I could do anything even when I did not believe it myself. To my mom and dad, Diane and Michael Burke, without your love and support I would not have made it this far. Thank you both for reminding me to take it easy every once in a while and coming to Tucson all those times I could not get away to see you. To my brother, Adam, thank you for always making me laugh when I needed it most. To my dear friend Sarah Marble, thank you for “talking me off the ledge” during prelims and every time science or life threw a curve ball at me. Finally, I want to dedicate this work to my perfect dogs Scout and Riley, although you missed out on many trips to the dog park and evening runs, you still loved me unconditionally and rested at my feet while I wrote most this. 6 TABLE OF CONTENTS LIST OF FIGURES............................................................................................. 11 LIST OF TABLES .............................................................................................. 15 ABSTRACT........................................................................................................ 16 CHAPTER 1: INTRODUCTION.......................................................................... 17 CHAPTER 2: AGE-ASSOCIATED CHANGES IN HIPPOCAMPAL PLASTICITY....................................................................................................... 29 2.1 Introduction ..................................................................................... 29 2.2 Morphology of the aging brain ...................................................... 30 2.3 Biophysical properties of aged hippocampal neurons ............... 35 2.4 Changes in hippocampal cell–cell interactions ........................... 37 CHAPTER 3: AGING ENSEMBLES: CIRCUIT CONTRIBUTIONS TO MEMORY DEFICITS ........................................................................................................... 51 3.1 Introduction..................................................................................... 51 3.2 Fundamental Properties of Place Cells in Young and old Rats............................................................................................ 53 3.3 Spike timing in the aged hippocampus ........................................ 58 3.4 Dynamic properties of hippocampal place cells in young and old rats .................................................................................................. 63 3.5 From the map to the memory in aging ensembles ...................... 75 CHAPTER 4: THE FUNCTION AND PHYSIOLOGY OF THE PERIRHINAL CORTEX ........................................................................................................... 87 4.1 Introduction..................................................................................... 87 4.2 Perirhinal cortical-dependent behavior in rats and monkeys .......................................................................................... 91 7 TABLE OF CONTENTS- continued 4.3 Biophysical and plasticity properties of perirhinal cortical neurons......................................................................................... 103 4.4 Single-unit activity of perirhinal cortical neurons in behaving animals ......................................................................................... 109 4.5 Discussion..................................................................................... 118 CHAPTER 5: THE HUMAN PERIRHINAL CORTEX AND PROCESS THEORIES OF RECOGNITION MEMORY...................................................... 120 5.1 Introduction..................................................................................