Estrogens and Brain Function : Neural Analysis of a Hormone-Controlled Mammalian Reproductive Behavior

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.

1 Introduction.- A. Approaching the Neural Mechanisms of Behavior.- B. Old Questions, New Tools.- C. Why Lordosis Behavior?.- 1. Hormones and Reproductive Behavior.- 2. Lordosis Behavior.- D. Behavioral Description of Lordosis.- 1 Triggering the Behavior: Sensory and Ascending Pathways.- 2 Stimulus.- A. Stimuli Applied by the Male.- B. Stimuli Necessary for Lordosis.- 1. Noncutaneous Stimuli Are Not Necessary.- 2. Cutaneous Stimuli.- C. Stimuli Sufficient for Lordosis.- D. Summary.- 3 Primary Sensory Neurons.- A. Distribution of Peripheral Sensory Nerves.- B. Sensory Neuron Types.- C. Quantitative Features of Responses.- 1. Thresholds.- 2. Receptive Fields.- 3. Time Course.- D. Effect of Estrogen.- E. Which Cells Trigger Lordosis?.- 1. Cutaneous Receptors Involved: A Process of Elimination.- 2. Requirements for Summation.- 3. F. Summary.- 4 Spinal Interneurons.- A. Distribution of Sensory Input.- B. Unit Types Defined by Sensory Input.- 1. Types Found.- 2. Locations in Cord.- 3. Comparison to Primary Sensory Units.- C. Quantitative Features of Neuronal Responses.- 1. Thresholds.- 2. Receptive Fields.- D. Implications.- 1. Which Interneurons Control Lordosis?.- 2. Convergence: Feature of Neuronal Responses and Mechanism of Summation.- 3. Unanswered Questions.- E. Summary.- 5 Ascending Neural Pathways.- A. No Lordosis in Spinal Rats.- B. Locations of Critical Pathways.- C. Projections of Ascending Pathways.- D. Responses of Cells in the Brainstem.- 1. Medulla.- 2. Midbrain.- E. Hypothalamic Cells Not on the Sensory Side of the Reflex Loop.- F. Summary and Implications.- 2 Facilitating the Behavior: Sex Hormones in the Brain.- 6 Steroid Sex Hormone Binding by Cells in the Vertebrate Brain.- A. Why Study Estrogen Binding?.- B. Estrogen Accumulation by Cells in Rat Central Nervous System.- 1. Autoradiographic Studies.- 2. Biochemical Studies.- C. Steroid Sex Hormone Binding by Cells in the Vertebrate Brain: From Fish to Philosopher.- D. Combinations of Steroid Hormone Autoradiography with Other Histochemical Identification Techniques.- E. Effects of Estrogen in the Hypothalamus.- 1. Morphological Effects.- 2. Electrophysiological Effects.- F. Implications of the Estrogen-Binding Processes.- 1. Correlations of Estrogen-Binding with Effects on Reproductive Behavior.- 2. Temporal Properties of Hypothalamic Participation.- 3. Aspects of Estrogen-Sensitive Neurons: Preliminary Ideas.- G. Summary.- 7 Hypothalamic Mechanisms.- A. Participation by Hypothalamic Cells in the Control of Lordosis.- 1. Lesion Studies.- 2. Electrical Stimulation.- 3. Summary.- B. Relationship to Control of Ovulation: Luteinizing Hormone-Releasing Hormone (LHRH).- C. Relationship of Female Behavior to Male Behavior and Autonomic Control Mechanisms: A Theory.- 1. Female Reproductive Function.- 2. Male Mating Behavior.- 3. Autonomic Function.- 4. Theory.- D. Source and Sign of Net Hypothalamic Influence on Lordosis Behavior.- E. Summary.- 8 Hypothalamic Outflow.- A. Introduction.- B. Preoptic Area.- C. Medial Anterior Hypothalamus.- D. Ventromedial Nucleus of the Hypothalamus.- E. Arcuate Nucleus.- F. Some Limbic Efferents.- G. Orderliness of Descending Axons: “Laminar Flow”.- 1. Medial-Lateral and Dorsal-Ventral Organization.- 2. Anterior-Posterior Organization: Laminar Flow.- 3. Conclusions.- H. Summary.- 9 Midbrain Module.- A. From Hypothalamus to Midbrain.- B. Proof of Modules in Brainstem.- C. Midbrain Central Gray Stimulation Enhances Lordosis; Lesions Disrupt It.- D. Electrophysiology of Midbrain Cells Projecting to the Medulla: Hormonal and Hypothalamic Effects on them.- 1. Electrophysiology of Midbrain Cells Projecting to the Medulla: Hormonal and Hypothalamic Effects on Them.- 2. Responses to Somatosensory Input.- 3. Synthesis.- E. Output Descending from the Midbrain.- F. Summary.- 3 Executive Control over the Behavior: Descending and Motor Pathways.- 10 Brainstem to Spinal Cord.- A. Descending Tracts to Be Considered.- B. Involvement of Descending Tracts in Lordosis.- 1. Tracts Not Involved.- 2. Tracts Involved.- C. Electrophysiology of Lateral Vestibulospinal and Lateral Reticulospinal Tracts.- 1. Lateral Vestibulospinal Tract: Background.- 2. Lateral (Medullary) Reticulospinal Tract: Background.- 3. Electrophysiological Experiments Related to Lordosis.- D. Implications.- 1. Specificity of Descending Control.- 2. Preparatory Nature of Descending Control.- 3. Courtship Behaviors Prepare for Lordosis Reflex.- E. Summary.- 11 Motoneurons and Response Execution.- A. Response Execution.- B. Muscles.- C. Motoneurons: Location.- D. Motoneurons: Physiology.- E. Summary.- 4 Building on this Paradigm.- 12 Logical and Heuristic Developments.- A. Introduction.- B. Economy in the Use of Ascending Sensory Information: The “Need to Know” Principle.- 1. Limited and Selective Distribution of Sensory Information.- 2. Permitting Neural Plasticity.- C. Additions and Interactions of Behavioral Causes by Nerve Cells: Analogy to “Switching Circuits” and “Threshold Logic”.- 1. Additions: The Role of Convergence.- 2. Interactions.- 3. Formal Descriptions of Behavioral Mechanisms: The Nervous System Can Be Logical.- D. Motivation: A Neural Mechanism for Sex Drive.- E. Ethological Concepts: Their Physiological Realization.- F. Progesterone Enhancement of Estrogen Action: Likely Mechanisms and Pathways Involved.- G. Economy in the Use of Descending Motor Executive Commands: The Issue of Behavioral Specificity.- 1. Economical Use of Descending Axons for Controlling Motor Systems.- 2. Chains of Response Can Produce a Cascade Effect.- 3. Chains of Courtship Responses Preparatory for Lordosis: Reflections on Neural State.- 4. Summary: Behavioral States Fostering Behavioral Acts.- H. Achieving Unity in an Organism’s Action.- 1. Hypothalamic Nerve Cells Adapt Endocrine, Behavioral, and Autonomic Responses to Environmental Constraints.- 2. Peptide-Releasing Hormones Synchronize Behavioral with Endocrine Events.- 3. Steroid Hormones Synchronize Behavioral Acts, Ovulation, and Uterine Preparation.- 4. Can We Generalize?.- 13 Summary.- 14 Epilogue.- A. Computability: Can This Be Done?.- 1. What Matters is What Counts—Or Is the Nervous System Logical?.- B. Morality: Should This Be Done?.- C. Extrapolation to Human Affairs.- D. Some Outstanding Questions.- References.