Table Of ContentDonald W. Pfaff
Estrogens and
Brain Function
Neural Analysis of a Hormone-Controlled
Mammalian Reproductive Behavior
With 109 Figures
Springer-Verlag
New York Heidelberg Berlin
DONALD W. PFAFF
Professor of Neurobiology and Behavior
The Rockefeller University
New York, New York 10021
USA
Library of Congress Cataloging in Publication Data
Pfaff, Donald W
Estrogens and brain function.
Includes index.
1. Reproduction. 2. Estrogen-Physiological effect.
3. Sexual behavior in animals. 4. Mammals-Behavior.
I. Title. [DNLM: 1. Estrogens-Physiology. 2. Brain
Physiology. 3. Sex behavior, Animal. 4. Posture.
5. Mammals. 6. Reproduction. QL761 P523e]
QP251.P47 599.01'6 80-11900
All rights reserved.
No part of this book may be translated or reproduced in any form
without written permission from Springer-Verlag.
The use of general descriptive names, trade 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.
© 1980 by Springer-Verlag New York Inc.
Softcover reprint of the hardcover 1s t edition 1980
9 8 7 6 5 4 3 2 1
ISBN-l3: 978-1-4613-8086-3 e-ISBN-13: 978-1-4613-8084-9
DOl: 10.1007/978-1-4613-8084-9
Preface
This book brings together some of the results and ideas produced by a
large number of people-colleagues and students with whom I am
privileged to work in the laboratory at Rockefeller University. In terms
of my personal history I see it as a confluence of creative forces
persons from whom I have learned. I was instructed in neuroanatomy by
Walle J. H. Nauta at M.I.T., and later in a course at Harvard Medical
School under the direction of Richard Sidman. At Harvard Medical
School, where M.I.T. graduate students were allowed to cross register,
the superb neurophysiology course was under the guiding spirit of
Stephen Kuffler. Later, I benefited greatly from participating in his
summer course in electrophysiological techniques at Woods Hole. Eric
Kandel and his colleagues have provided us with the most exciting
contemporary approach to the conceptualization and study of cellular
mechanisms for behavior. Here at Rockefeller, Carl Pfaffmann and Neal
Miller have been leaders in every sense of the word. Not only did they
provide me with opportunities to grow to scientific maturity; they also
set an example of clear thinking about mechanisms for mammalian
behavior patterns.
I wrote this book to show how the systematic use of increasingly
detailed electrophysiological, neuroanatomical, and neuroendocrine tech
niques can explain the mechanism for a mammalian behavioral response.
The behavior in question happens to be sensitive to steroid hormones
and plays a central role in reproduction. The writing is intended to be
clear enough to enable any person who enjoys Scientific American or
Nature to understand the main lines of data presentation and thought.
The presentation is also precise enough that trained researchers and
students who can detect gaps or shortcomings may be encouraged to fill
them by doing new experiments.
Rockefeller University DONALD W. PFAFF
New York
January 1980
Contents
Chapter 1
Introduction
A. Approaching the Neural Mechanisms of Behavior 1
B. Old Questions, New Tools 2
C. Why Lordosis Behavior? 4
1. Hormones and Reproductive Behavior 4
2. Lordosis Behavior 4
D. Behavioral Description of Lordosis 6
Part 1
Triggering the Behavior: Sensory and
Ascending Pathways
Chapter 2
Stimulus
A. Stimuli Applied by the Male 19
B. Stimuli Necessary for Lordosis 20
1. Noncutaneous Stimuli Are Not Necessary 20
2. Cutaneous Stimuli 21
C. Stimuli Sufficient for Lordosis 24
D. Summary 30
vi Contents
Chapter 3
Primary Sensory Neurons
A. Distribution of Peripheral Sensory Nerves 31
B. Sensory Neuron Types 35
C. Quantitative Features of Responses 37
1. Thresholds 37
2. Receptive Fields 38
3. Time Course 38
D. Effect of Estrogen 39
E. Which Cells Trigger Lordosis? 40
1. Cutaneous Receptors Involved: A Process of Elimination 40
2. Requirements for Summation 42
F. Summary 43
Chapter 4
Spinal Interneurons
A. Distribution of Sensory Input 44
B. Unit Types Defined by Sensory Input 46
1. Types Found 46
2. Locations in Cord 51
3. Comparison to Primary Sensory Units 51
C. Quantitative Features of Neuronal Responses 52
1. Thresholds 52
2. Receptive Fields 52
D. Implications 53
1. Which Interneurons Control Lordosis? 53
2. Convergence: Feature of Neuronal Responses and
Mechanism of Summation 54
3. Unanswered Questions 55
E. Summary 56
Chapter 5
Ascending Neural Pathways
A. No Lordosis in Spinal Rats 57
B. Locations of Critical Pathways 57
C. Projections of Ascending Pathways 61
D. Responses of Cells in the Brainstem 64
1. Medulla 64
2. Midbrain 69
E. Hypothalamic Cells Not on the Sensory Side of the
Reflex Loop 71
F. Summary and Implications 71
Contents vii
Part 2
Facilitating the Behavior: Sex Hormones
in the Brain
Chapter 6
Steroid Sex Hormone Binding by Cells in the
Vertebrate Brain
A. Why Study Estrogen Binding? 77
B. Estrogen Accumulation by Cells in Rat Central
Nervous System 79
1. Autoradiographic Studies 79
2. Biochemical Studies 85
C. Steroid Sex Hormone Binding by Cells in the Vertebrate
Brain: From Fish to Philosopher 86
D. Combinations of Steroid Hormone Autoradiography
with Other Histochemical Identification Techniques 94
E. Effects of Estrogen in the Hypothalamus 96
1. Morphological Effects %
2. Electrophysiological Effects 97
F. Implications of the Estrogen-Binding Processes 100
1. Correlations of Estrogen-Binding with Effects on
Reproductive Behavior 100
2. Temporal Properties of Hypothalamic Participation 103
3. Aspects of Estrogen-Sensitive Neurons: Preliminary Ideas 103
G. Summary 103
Chapter 7
Hypothalamic Mechanisms
A. Participation by Hypothalamic Cells in the Control
of Lordosis 106
1. Lesion Studies 107
2. Electrical Stimulation 112
3. Summary 114
B. Relationship to Control of Ovulation: Luteinizing Hormone-
Releasing Hormone (LHRH) 116
C. Relationship of Female Behavior to Male Behavior and
Autonomic Control Mechanisms: A Theory 118
1. Female Reproductive Function 118
2. Male Mating Behavior 120
3. Autonomic Function 121
4. Theory 123
viii Contents
D. Source and Sign of Net Hypothalamic Influence on
Lordosis Behavior 123
E. Summary 127
Chapter 8
Hypothalamic Outflow
A. Introduction 128
B. Preoptic Area 129
C. Medial Anterior Hypothalamus 133
D. Ventromedial Nucleus of the Hypothalamus 136
E. Arcuate Nucleus 138
F. Some Limbic Efferents 139
G. Orderliness of Descending Axons: "Laminar Flow" 140
1. Medial-Lateral and Dorsal-Ventral Organization 140
2. Anterior-Posterior Organization: Laminar Flow 142
3. Conclusions 143
H. Summary 144
Chapter 9
Midbrain Module
A. From Hypothalamus to Midbrain 147
B. Proof of Modules in Brainstem 147
C. Midbrain Central Gray Stimulation Enhances Lordosis;
Lesions Disrupt It 152
D. Electrophysiology of Midbrain Cells Projecting to the
Medulla: Hormonal and Hypothalamic Effects on them 159
1. Electrophysiology of Midbrain Cells Projecting to
the Medulla: Hormonal and Hypothalamic Effects on Them 159
2. Responses to Somatosensory Input 162
3. Synthesis 163
E. Output Descending from the Midbrain 163
F. Summary 165
Part 3
Executive Control over the Behavior:
Descending and Motor Pathways
Chapter 10
Brainstem to Spinal Cord
A. Descending Tracts to Be Considered 171
B. Involvement of Descending Tracts in Lordosis 171
Contents IX
1. Tracts Not Involved 171
2. Tracts Involved 174
C. Electrophysiology of Lateral Vestibulospinal and Lateral
Reticulospinal Tracts 179
1. Lateral Vestibulospinal Tract: Background 179
2. Lateral (Medullary) Reticulospinal Tract: Background 182
3. Electrophysiological Experiments Related to Lordosis 185
D. Implications 189
1. Specificity of Descending Control 189
2. Preparatory Nature of Descending Control 190
3. Courtship Behaviors Prepare for Lordosis Reflex 191
E. Summary 193
Chapter 11
Motoneurons and Response Execution
A. Response Execution 195
B. Muscles 196
C. Motoneurons: Location 200
D. Motoneurons: Physiology 204
E. Summary 206
Part 4
Building on this Paradigm
Chapter 12
Logical and Heuristic Developments
A. Introduction 211
B. Economy in the Use of Ascending Sensory
Information: The "Need to Know" Principle 211
1. Limited and Selective Distribution of Sensory
Information 211
2. Permitting Neural Plasticity 212
C. Additions and Interactions of Behavioral Causes by
Nerve Cells: Analogy to "Switching Circuits" and
"Threshold Logic"
213
1. Additions: The Role of Convergence 213
2. Interactions 214
3. Formal Descriptions of Behavioral Mechanisms:
The Nervous System Can Be Logical 215
D. Motivation: A Neural Mechanism for Sex Drive 217
x Contents
E. Ethological Concepts: Their Physiological Realization 219
F. Progesterone Enhancement of Estrogen Action: Likely
Mechanisms and Pathways Involved 220
G. Economy in the Use of Descending Motor Executive
Commands: The Issue of Behavioral Specificity 223
1. Economical Use of Descending Axons for Controlling
Motor Systems 224
2. Chains of Response Can Produce a Cascade Effect 224
3. Chains of Courtship Responses Preparatory for
Lordosis: Reflections on Neural State 228
4. Summary: Behavioral States Fostering Behavioral Acts 229
H. Achieving Unity in an Organism's Action 231
1. Hypothalamic Nerve Cells Adapt Endocrine,
Behavioral, and Autonomic Responses to
Environmental Constraints 233
2. Peptide-Releasing Hormones Synchronize Behavioral
with Endocrine Events 233
3. Steroid Hormones Synchronize Behavioral Acts,
Ovulation, and Uterine Preparation 234
4. Can We Generalize? 234
Chapter 13
Summary 235
Chapter 14
Epilogue
A. Computability: Can This Be Done? 240
1. What Matters is What Counts -Or Is the
Nervous System Logical? 241
B. Morality: Should This Be Done? 242
C. Extrapolation to Human Affairs 245
D. Some Outstanding Questions 246
References 249
Index 275
Chapter 1
Introduction
A. Approaching the Neural Mechanisms of
Behavior
Those who study the nervous sytem ultimately aim to explain behavior.
They intend to demonstrate how behavioral responses are produced as
a function of nerve cell activity. However, even for small bits of neural
tissue and restricted forms of behavior, the numbers of nerve cells to be
considered are so large and their connections so complex that all sorts
of explanatory hypotheses can be imagined. As a result, in the history
of neural and behavioral studies, many thinkers have felt free to "neu
rologize." They could speculate broadly about the overall "organization
of the brain" and the control of behavior because, virtually always, the
number of facts available to rule out their hypotheses was small. No
comprehensive model or hypothesis could be shown to be better than
others.
It has therefore been necessary to choose a behavioral problem for
which it would be fruitful to gather a great number of behavioral,
neuroanatomical, and neurophysiological facts that may be used to
narrow down the allowable hypotheses to a small number. With enough
of these relevant facts brought to bear, the logical scientific procedure of
strong inference (Platt, 1964) can be used to arrive at satisfactory models
and hypotheses. In turn, principles can be stated clearly and tested.
This approach discourages the practice of concentrating on a single
region of neural tissue, doing a great deal of experimental work on that
region, and asking the question, "What does this tissue do?" One does
not take a single experimental technique and apply it to all neural tissue
and functional problems available. Rather, the objective is to try to see
how the nervous system accomplishes a particular "job": that is, we
choose a particular pattern of adaptive behavior and investigate how the
nervous system produces and controls that behavior. From this infor-
