Table Of ContentNeurotransmitter
Interactions and
Cognitive Function
COVER: Cluster of cholinergic neurons in the basal nuclear complex of a rat
demonstrated by choline acetyltransferase immunohistochemistry. The overlap
ping 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 Michael W. Decker
Department of Psychiatry Abbott Laboratories
Duke University Medical Center Abbott Park, IL 60064
Durham, NC 27710 USA
USA
Larry L. Butcher
Laboratory of Chemical Neuroanatomy
Department of P,ychology
University of California
Los Angeles, CA 90024-1563
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 92-17848
CIP
Printed on acid-free paper.
© 1992 Birkhauser Boston
Softcover reprint of the hardcover 1s t edition 1992
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ISBN-13: 978-1-4615-9845-9 e-ISBN-13: 978-1-4615-9843-5
DOl: 10.1007/978-1-4615-9843-5
Typeset by Allis Graphics and Design, Mechanicsburg, PA
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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
Contents
VI
8 Neurotransmitter Interactions and Responsivity to
Cholinomimetic Agents
V. Haroutunian, A.C. Santucci, and K.L. Davis . · .118
9 The Importance of DI and D2 Interactions with Nicotinic and
Muscarinic Systems for Working Memory Function
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 .......... . .240
16 Potentiation of the Effects of Antimuscarinic Drugs on Behavior
by Serotonin Depletion: Specificity and Relation to Learning
and Memory
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 . ............. . · .277
18 Intraseptal GABAergic Infusions Disrupt Memory in the Rat:
Method and Mechanisms
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 develop
ment 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
