University of Massachusetts Amherst ScholarWorks@UMass Amherst Open Access Dissertations 2-2010 Vasopressin Anatomy of the Mouse Brain Benjamin D. Rood University of Massachusetts Amherst Follow this and additional works at: https://scholarworks.umass.edu/open_access_dissertations Part of the Behavior and Behavior Mechanisms Commons, and the Neurology Commons Recommended Citation Rood, Benjamin D., "Vasopressin Anatomy of the Mouse Brain" (2010). Open Access Dissertations. 200. https://scholarworks.umass.edu/open_access_dissertations/200 This Open Access Dissertation is brought to you for free and open access by ScholarWorks@UMass Amherst. It has been accepted for inclusion in Open Access Dissertations by an authorized administrator of ScholarWorks@UMass Amherst. For more information, please contact [email protected]. VASOPRESSIN ANATOMY OF THE MOUSE BRAIN A Dissertation Presented by BENJAMIN D. ROOD Submitted to the Graduate School of the University of Massachusetts Amherst in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY February 2010 Neuroscience and Behavior © Copyright by Benjamin D. Rood 2010 All Rights Reserved VASOPRESSIN ANATOMY OF THE MOUSE BRAIN A Dissertation Presented by BENJAMIN D. ROOD Approved as to style and content by: _________________________________________________ Geert J. de Vries, Chair _________________________________________________ John R. Nambu, Member _________________________________________________ Jeffrey D. Blaustein, Member _________________________________________________ Nancy G. Forger, Member _____________________________________________ Jerrold S. Meyer, Director Neuroscience and Behavior DEDICATION To my loving wife and two beautiful children. ACKNOWLEDGEMENTS I would like to thank my advisor Geert J. de Vries for the many years of guidance and support that he has given me. I am also especially grateful for his having believed in me even when I no longer believed in myself. Thank you to my dissertation committee, Nancy Forger, Jeff Blaustein, and John Nambu, whose feedback has always made me a better writer and scientist. To the many students and technicians that have assisted me over the last decade, thank you. Thank you to my friends Marianne Seney and, especially, Elaine Murray, who have always been there to encourage me and help me get to the next day. Finally, to my wife and children, I love you. Without your support and understanding the writing of this dissertation would not have been possible. You inspire me. v ABSTRACT VASOPRESSIN ANATOMY OF THE MOUSE BRAIN FEBRUARY 2010 BENJAMIN D. ROOD, B.S., BATES COLLEGE M.S., UNIVERSITY OF MASSACHUSETTS AMHERST Ph.D., UNIVERSITY OF MASSACHUSETTS AMHERST Directed by: Geert J. de Vries The nine amino acid peptide vasopressin acts as a neurohormone in the periphery and a neurotransmitter / neuromodulator in the central nervous system. Historically, research on vasopressin neurons and their projections to the pituitary has helped lay the groundwork for our understanding of peptidergic neurotransmission. Currently, our research on central vasopressin projections is driving a revolution in our understanding of social behavior. Vasopressin affects a number of social behaviors from social memory to aggression to affiliative behavior, such as pair-bonding. Further, with the addition of more and more transgenic mouse models of disease states, anxiety and depression related disorders, and social behavior dysfunction, it is important now more than ever to have a clear knowledge of the mouse vasopressin system, which derives from a number of distinct nuclei within the brain. Here, I map out vasopressin immunoreactivity in the mouse brain, and delineate the subset of brain regions with gonadal steroid hormone- dependent vasopressin immunoreactivity. Such projections are thought to derive from the bed nuclei of the stria terminalis and medial amygdala in the telencephalon. Finally, based on data from mice with lesions of the suprachiasmatic nucleus, I outline the subset of regions that likely receive vasopressin from this source. Our research on the anatomy of the vasopressin system of mice and our attempts to delineate the site of origin of the many vasopressin fibers found throughout the brain suggest that a significant amount of the vasopressin innervation deriving from cells in the bed nuclei of the stria terminalis and medial amygdala project to areas in the midbrain involved in serotonin and dopamine transmission, such as the dorsal raphe and ventral tegmental area. These transmitter systems play a crucial role in the control of anxiety and depression levels as well as motivated behavior and emotional regulation. Our results strongly suggest that a direct link exists between these systems, and future plans include an examination of this possibility. It is our hope that this work will further our understanding of the role of vasopressin and other transmitter systems in the regulation of social behaviors. vi TABLE OF CONTENTS Page ACKNOWLEDGMENTS .............................................................................................v ABSTRACT................................................................................................................. vi LIST OF TABLES...................................................................................................... xii LIST OF FIGURES ................................................................................................... xiii CHAPTER 1. THE VASOPRESSIN SYSTEM ..............................................................................1 1.1 Introduction.................................................................................................1 1.2 Vasopressin is a peptide..............................................................................1 1.3 Vasopressin acts as a neurotransmitter .......................................................2 1.4 Location of vasopressin production............................................................4 1.5 Regulation of vasopressin gene expression ................................................5 1.6 Location of vasopressin-containing fibers..................................................7 1.7 Site of origin of vasopressin-containing fibers .........................................10 1.8 Vasopressin receptors ...............................................................................12 1.9 Functions carried out by vasopressin........................................................13 1.10 Summary.................................................................................................15 2. VASOPRESSIN ANATOMY IN INTACT MALES.............................................16 2.1 Introduction...............................................................................................16 2.2 Methods.....................................................................................................19 2.2.1 Animals......................................................................................19 2.2.2 Tissue collection and processing ...............................................20 2.2.3 Nissl staining..............................................................................20 2.2.4 Immunohistochemistry..............................................................21 2.2.5 Analyses and image acquisition.................................................22 2.3 Results.......................................................................................................22 2.3.1 Cell bodies in the diencephalon .................................................24 2.3.1.1 Paraventricular nucleus...............................................24 2.3.1.2 Supraoptic nucleus......................................................24 2.3.1.3 Suprachiasmatic nucleus.............................................25 2.3.1.4 Accessory nuclei.........................................................25 vii 2.3.1.5 Other hypothalamic nuclei..........................................26 2.3.2 Cell bodies in the telencephalon ................................................26 2.3.2.1 Bed nuclei of the stria terminalis ................................26 2.3.2.2 Medial Amygdala........................................................27 2.3.3 Small versus medium fibers.......................................................27 2.3.4 Fibers in the telencephalon ........................................................28 2.3.4.1 Cortex..........................................................................28 2.3.4.2 Hippocampus ..............................................................28 2.3.4.3 Basal ganglia...............................................................29 2.3.4.4 Septal Complex...........................................................30 2.3.4.5 Ventral forebrain.........................................................31 2.3.4.6 Bed nuclei of the stria terminalis ................................31 2.3.4.7 Amygdala....................................................................32 2.3.5 Fibers in the diencephalon .........................................................34 2.3.5.1 Hypothalamus .............................................................34 2.3.5.1.1 Preoptic Area...............................................34 2.3.5.1.2 Anterior hypothalamus.................................35 2.3.5.1.3 Dorsomedial hypothalamus .........................36 2.3.5.1.4 Lateral hypothalamus...................................37 2.3.5.1.5 Mammillary bodies......................................37