Estrogens and Brain Function

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 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-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-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.