Neurotransmitter Interactions and

Cognitive Function

COVER: Cluster of cholinergic neurons in the basal nuclear complex of a rat demonstrated by choline acetyltransferase immunohistochemistry. The overlap­ping dendrites and logic symbols suggest the rich interactions and complex computational operations that could occur in this region of the brain in relation to cognitive function. Photomicrograph from the laboratory of Larry L. Butcher.

Neurotransmitter Interactions and

Cognitive Function

Edward D. Levin Michael W. Decker

Larry L. Butcher Editors

James L. McGaugh Foreword

73 Illustrations with some color

Birkhiiuser Boston • Basel • Berlin

Edward D. Levin Department of Psychiatry Duke University Medical Center Durham, NC 27710 USA

Larry L. Butcher Laboratory of Chemical Neuroanatomy Department of P,ychology University of California Los Angeles, CA 90024-1563 USA

Michael W. Decker Abbott Laboratories Abbott Park, IL 60064 USA

Library of Congress Cataloging-in-Publication Data

Neurotransmitter interactions and cognitive function / Edward D. Levin, Michael Decker, Larry L. Butcher, editors.

p. cm. Includes bibliographical references and index.

I. Neurotransmitters. 2. Cognition. 3. Cognitive neuroscience. /. Levin, Edward D. ll. Decker, Michael, 1951- III. Butcher, Larry L.

lDNLM: I. Cognition-physiology--congresses. 2. Neuroregulators­-physiology--congresses. QV 126 N49385] QP364.7.N468 1992 612.8'2-Dc20 DNLMIDLC for Library of Congress

Printed on acid-free paper.

© 1992 Birkhauser Boston

Softcover reprint of the hardcover 1 st edition 1992

92-17848 CIP

Copyright is not claimed for works of U.S. Government employees. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without prior permission of the copyright owner. The use of general descriptive names, trademarks, etc. in this publication even if the former are not especially identified, is not to be taken as a sign that such names, as understood by the Trade Marks and Merchandise Marks Act, may accordingly be used freely by anyone. Permission to photocopy for internal or personal use, or the internal or personal use of specific clients, is granted by Birkhauser Boston for libraries and other users registered with the Copyright Clearance Center (CCC), provided that the base fee of $5.00 per copy, plus $0.20 per page is paid directly to CCC, 21 Congress Street, Salem, MA 01970, U.S.A. Special requests should be addressed directly to Birkhiiuser Boston, 675 Massachusetts Avenue, Cambridge, MA 02139, U.S.A.

ISBN-13: 978-1-4615-9845-9

DOl: 10.1007/978-1-4615-9843-5

e-ISBN-13: 978-1-4615-9843-5

Typeset by Allis Graphics and Design, Mechanicsburg, PA

9 8 7 6 5 432 I

Contents

Foreword James L. McGaugh IX

Preface ...... . . X

List of Contributors . . . . . . . . . . . . . . . . . . . . . . . xi

Interactions among Neurotransmitters: Their Importance to the "Integrated Organism" Roger W. Russell . . . . . . . . . . . . . . . . . . . . . . . .

2 The Cholinergic Basal Forebrain and its Telencephalic Targets: Interrelations and Implications for Cognitive Function Larry L. Butcher. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 15

3 Synaptic Organization of Basal Forebrain Cholinergic Projection Neurons Laszlo Zaborszky. . . . . . . . . . . . . . . . . . . . .. ...... 27

4 Functional Pharmacology of Basal Forebrain Dopamine T. Celeste Napier . . . . . . . . . . . . . . . . . . .. ...... 66

5 Cholinergic/Noradrenergic Interactions and Memory Michael W. Decker . . . . . . . . . . . . . . . . . . . . . . . 78

6 The Role of the Noradrenergic System in Higher Cerebral Functions-Experimental Studies About the Effects of Noradrenergic Modulation on Electrophysiology and Behavior Paavo J. Riekkinen, Jouni Sirvio, Paavo Riekkinen Jr., Antti Va ljakka , Pekka Jiikiilii, Esa Koivisto, and Risto Lammintausta . . . . . . . . . . . . . . . . . . . . . . . . . . . 91

7 Septal Noradrenergic and Glutamatergic Influences on Hippocampal Cholinergic Activity in Relation to Spatial Learning and Memory in Mice Robert Jaffard, Aline Marighetto, and Jacques Micheau ...... 103

VI Contents

8 Neurotransmitter Interactions and Responsivity to Cholinomimetic Agents V. Haroutunian, A.C. Santucci, and K.L. Davis .

9 The Importance of DI and D2 Interactions with Nicotinic and Muscarinic Systems for Working Memory Function

· .118

Edward D. Levin and Jed E. Rose .................. 144

10 Neurotransmitter Systems in Hippocampus and Prelimbic Cortex, Dopamine-Acetylcholine Interactions in Hippocampus, and Memory in the Rat Gilberto N.O. Brito. . . . . . . . . . . . . . . . . . . . . . . 159

11 Nicotinic-Muscarinic Interactions in Cognitive Function Edward D. Levin and Roger W. Russell . . . . . . . .. . .... 183

12 The Influence of Neurotensin upon Cholinergic Function Gary L. Wenk . . . . . . . . . . . . . . . . . . . . . . .. . .... 196

13 Serotonin Influences on Cholinergic Function: Possible Interactions in Learning and Memory Howard J. Normile and Harvey J. Altman . ............. 207

14 The Contribution of the Serotonergic Innervation of the Hippocampus to the Effects of Combined Cholinergic/ Serotonergic Deficits Gal Richter-Levin and Menahem Segal . ........ . · .228

15 Overlapping Neural Substrates Underlying Defense Reactions, Aversive Memory, and Convulsive Behavior Carlos Tomaz, Marcus L. Brandiio, and Norberto Garcia-Cairasco .......... .

16 Potentiation of the Effects of Antimuscarinic Drugs on Behavior by Serotonin Depletion: Specificity and Relation to Learning and Memory

.240

C.H. Vanderwolf and D. Penava . . . . . . . . . . . . .. . .. 257

17 Interactions of Neurotransmitters and Neuroanatomy: It's Not What You Do, It's the Place that You Do It David S. Olton and Kevin Pang . ............. .

18 Intraseptal GABAergic Infusions Disrupt Memory in the Rat: Method and Mechanisms

· .277

James J. Chrobak and T. Celeste Napier . .............. 287

Contents vii

19 Working Memory and Cholinergic Autoregulation in the Medial Septal Area Bennet Givens and David Olton .................... 301

20 Modulation of Memory by Benzodiazepine-Acetylcholine Interactions Thomas J. Walsh and Robert W. Stackman ............. 312

21 Cognition Enhancement Based on GABA-Cholinergic Interactions Martin Sarter, Paul Dudchenko, Holly Moore, Lee Ann Holley, and John P. Bruno ................. 329

22 Transmitter Interactions and Cognitive Function: Appreciation of the Concert Edward D. Levin, Michael Decker, and Larry L. Butcher. . . . . 355

Foreword JAMES L. MCGAUGH

Understanding of the nature and functions of neurotransmitter systems in the brain has increased enormously in recent decades. Lack of knowledge required us, not too long ago, to use the adjective "putative" when discussing transmitters. Such caution is no longer essential (at least for a number of transmitters). Impressive progress has been achieved in understanding the pharmacology, biochemistry and anatomy of transmitter systems. There has, however, been relatively less progress in understanding the functioning of brain transmitters in regulating and mediating behavior. A simple and certainly correct explanation for this is, of course, that understanding of neurotransmitter functions requires prior detailed knowledge of basic pharmacology, biochemistry and anatomy. Beyond that, it now seems likely that progress in understanding the functions of brain neurotransmitters will proceed only as we examine the interactions of neurotransmitter systems in regulating behavioral functions. This premise is, of course, suggested by the findings of studies of the chemical neuroanatomy of the brain: Neurotransmitter systems are influenced by other neurotransmitter systems and, in tum, influence the same as well as other systems. No system works alone. The chapters in this book explicitly examine the interactions of neurotransmitter systems involved in the regulation of cognitive processes. The facts and interpretations offered provide compelling support for the premise that cognitive processes are orchestrated by interactions among neurotransmitter systems. And, they offer promise that understanding of such interactions will be of critical importance in the develop­ment of treatments for brain diseases affecting cognitive functioning.

James L. McGaugh Center for the Neurobiology of Learning and Memory and Department of Psychobiology University of California, Irvine

May 1992

Preface

Cholinergic systems have been extensively studied over a period of decades as neural substrates for cognitive function. However, acetylcholine is not monolithic in its importance for learning and memory. A variety of other transmitter systems, including dopamine, norepinephrine, serotonin, and GABA, have also been found to be critical for cognitive processing. Recently, the study of transmitter system involvement in cognitive function has evolved to the point where interactions between transmitter systems has become a focus of investigation. This involves a transition in thinking from a reductionistic approach to determine the critical involvement of specific anatomic and physiological processes in cognitive function to an integrative approach to determine how neural systems interact to form the complex nature of cognition.

The purpose of this volume is to convey the importance of the study of neural integration as well as to elucidate the specific details of the anatomical and physiological interations of transmitter systems with regard to cognitive function. This project began with a Satellite Symposium to the Society for Neuroscience meeting in New Orleans on November 10, 1991. Participants of that symposium, as well as additional experts in the field, have contributed chapters for this book. We hope that this volume is not only useful in the transmission of new information about the importance of neural integration for cognitive function, but that it also serves to encourage the interaction of scientists studying a variety of systems to further advance our understanding of neurobehavioral relationships.

We would like to thank the following companies for their support of this endeavor: Abbott Laboratories; Roerig, a division of Pfizer Pharmaceuticals; Hoechst-Roussel Pharmaceuticals; and Schering-Plough Research.

Edward D. Levin Michael W. Decker Larry L. Butcher

March 1992

List of Contributors

Harvey J. Altman, Department of Psychiatry, Wayne State University School of Medicine, Lafayette Clinic, Detroit, Michigan 48207, USA

Marcus L. Brandao, Laboratory of Psychobiology, FFCLRP, University of Sao Paulo, 14.049 Ribeirao Preto, SP, Brazil

Gilberto N. O. Brito, Setor de Neurociencias, Universidade Federal Fluminense, Niteroi, RJ 24001, Brazil

John P. Bruno, Department of Psychology and Neuroscience Program, Ohio State University, Columbus, Ohio 43210, USA

Larry L. Butcher, Laboratory of Chemical Neuroanatomy, Department of Psychology, University of California, Los Angeles, California 90024-1563, USA

James J. Chrobak, Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, New Jersey 07102, USA

Kenneth L. Davis, Department of Psychiatry, The Mount Sinai School of Medicine, New York, New York 10029-6574, USA

Michael W. Decker, Abbott Laboratories, Abbott Park, Illinois 60064, USA

Paul Dudchenko, Department of Psychology and Neuroscience Program, Ohio State University, Columbus, Ohio 43210, USA

Norberto Garcia-Cairasco, Neurophysiology and Neuroethology Laboratory, FMRP, University of Sao Paulo, SP, Brazil

Bennet Givens, Department of Psychology, Ohio State University, Columbus, Ohio 43210, USA

Vahram Haroutunian, Department of Psychiatry, The Mount Sinai School of Medicine, New York, New York 10029-6574, USA

xii List of Contributors

Lee Ann Holley, Department of Psychology and Neuroscience Program, Ohio State University, Columbus, Ohio 43210, USA

Robert JafTard, Laboratoire de Neurosciences Comportementales et Cognitives, URA CNRS, Universite de Bordeaux I, Institut de Biologie Animale, 33405 Talence Cedex, France

Pekka Jakala, Department of Neurology, University of Kuopio, SF-70211 Kuopio, Finland

Esa Koivisto, Department of Neurology, University of Kuopio, SF-70211 Kuopio, Finland

Risto Lammintausta, Orion Corporation FARMOS, R&D Pharmaceuticals, SF-20101 Turku, Finland

Edward D. Levin, Department of Psychiatry, Duke University Medical Center, Behavioral Neuroscience Laboratory, Box 3557, Durham, North Carolina 27710, USA

Aline Marighetto, Laboratoire de Neurosciences Comportementales et Cogni­tives, URA CNRS, Universite de Bordeaux I, lnstitut de Biologie Animale, 33405 Talence Cedex, France

Jacques Micheau, Laboratoire de Neurosciences Comportementales et Cogni­tives, URA CNRS, Universite de Bordeaux I, lnstitut de Biologie Animale, 33405 Talence Cedex, France

Holly Moore, Department of Psychology and Neuroscience Program, Ohio State University, Columbus, Ohio 43210, USA

T. Celeste Napier, Department of Pharmacology , and the Neuroscience Program, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois 60153, USA

Howard J. Normile, Department of Psychiatry, Wayne State University School of Medicine, Lafayette Clinic, Detroit, Michigan 48207, USA

David S. Olton, Department of Psychology, The Johns Hopkins University, Baltimore, Maryland 21218, USA

Kevin Pang, Department of Psychology, The Johns Hopkins University, Balti­more, Maryland 21218, USA

List of Contributors xiii

D. Penava, Department of Psychology, University of Western Ontario, London, Ontario, Canada N6A 5C2

Gal Richter-Levin, The Department of Neurobiology , The Weizmann Institute of Science, Rehovot 76100, Israel

Paavo J. Riekkinen, Department of Neurology , University of Kuopio, SF-70211 Kuopio, Finland

Paavo Riekkinen, Jr., Department of Neurology, University of Kuopio, SF-70211 Kuopio, Finland

Jed E. Rose, Department of Psychiatry, Duke University Medical Center, Nicotine Research Laboratory, V A Medical Center, Durham, North Carolina 27705, USA

Roger W. Russell, Center for the Neurobiology of Learning and Memory and the Department of Psychobiology, University of California, Irvine, California 92717, USA

A. C. Santucci, Department of Psychology, Manhattanville College, Purchase, New York 10577, USA

Martin Sarter, Department of Psychology and Neuroscience Program, Ohio State University, Columbus, Ohio 43210, USA

Menahem Segal, The Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel

Jouni Sirvio, Department of Neurology, University of Kuopio, SF-70211 Kuopio, Finland

Robert W. Stackman, Department of Psychology, Rutgers University, New Brunswick, New Jersey 08903, USA

Carlos Tomaz, Laboratory of Psychobiology , FFCLRP, University of Sao Paulo, SP, Brazil

Antti Valjakka, Department of Neurology, University of Kuopio, SF-70211 Kuopio, Finland

C. H. Vanderwolf, Department of Psychology, University of Western Ontario, London, Ontario, Canada N6A 5C2

xiv List of Contributors

Thomas J. Walsh, Department of Psychology, Rutgers University, New Bruns­wick, New Jersey 08903, USA

Gary L. Wenk, Division of Neural Systems, Memory, and Aging, University of Arizona, Tucson, Arizona 85724, USA

Laszlo Zaborszky, Departments of Neurology, Neurosurgery, and Otolaryngol­ogy, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA