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Donald W. Pfaff
Nora D. Volkow
Editors-in-Chief

Neuroscience
in the
21st Century
From Basic to Clinical
Second Edition
Neuroscience in the 21st Century
Donald W. Pfaff • Nora D. Volkow
Editors-in-Chief

Neuroscience in the
21st Century
From Basic to Clinical

Second Edition

With 1294 Figures and 107 Tables

Editors-in-Chief
Donald W. Pfaff Nora D. Volkow
Laboratory of Neurobiology and Behavior National Institute on Drug Abuse (NIDA)
The Rockefeller University National Institutes of Health (NIH)
New York, NY, USA Rockville, MD, USA

ISBN 978-1-4939-3473-7 ISBN 978-1-4939-3474-4 (eBook)

ISBN 978-1-4939-3487-4 (print and electronic bundle)
DOI 10.1007/978-1-4939-3474-4
Library of Congress Control Number: 2016949741

1st edition: # Springer Science+Business Media, LLC 2013

# Springer Science+Business Media New York 2016
This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the
material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,
broadcasting, reproduction on microfilms or in any other physical way, and transmission or information
storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology
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The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication
does not imply, even in the absence of a specific statement, that such names are exempt from the relevant
protective laws and regulations and therefore free for general use.
The publisher, the authors and the editors are safe to assume that the advice and information in this book
are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the
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or omissions that may have been made.

Printed on acid-free paper

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The registered company is Springer Science+Business Media LLC
The registered company address is 233 Spring Street, New York, NY 10013, U.S.A.
Preface to the Second Edition

The primary purpose of this project has been to produce a comprehensive, electronic
introduction to current-day neuroscience in a didactic form useful for upper-level
premedical students, entering medical students, and graduate students in a wide
variety of countries, with an emphasis on economically developing countries. The
Supervisory Editors and the authors, in their international distribution, reflect our
intention to recognize the growing interest in neuroscience and expertise across the
world.

Neuroscience Addresses Medical and Public Health Problems,

Worldwide

Neuroscience research provides basic discoveries about how the brain works and
how it controls behavior and how its disruption can result in neurological and
psychiatric disorders. These discoveries are of relevance for improving multiple
outcomes that span from health (i.e., how to maximize cognitive performance and
optimize well being) to education (i.e., how to use knowledge from neuroscience on
how the brain learns to improve the delivery of education). Neuroscience broadly
defined also offers pivotal components of both medical education and the delivery of
medical services. For example, depression and schizophrenia – once viewed as
purely “behavioral” problems – are now candidates for neurochemical/neurophar-
macological treatments. Similarly addiction, which was once viewed as a condition
of moral weakness, is now recognized as a disease of the brain with impairment
in specific brain circuits. Degenerative conditions such as neurosyphilis,
HIV-associated dementia, traumatic brain injury, and Alzheimer can now be delayed
by science-based treatments. Coma and persistent vegetative state are approached by
manipulating brain mechanisms responsible for arousal. Indeed, as neuroscience
explores the etiology of disease – the complex interplay between biological, psy-
chological, and sociocultural factors – it is increasingly valuable in understanding an
array of diseases. A recent report by the Surgeon General, in the USA, cites several
such diseases: schizophrenia, bipolar disorder, early onset depression, autism, atten-
tion deficit/hyperactivity disorder, anorexia nervosa, substance use disorders, and
panic disorder, among many others.

v
vi Preface to the Second Edition

The Surgeon General states that in the USA, the 1-year prevalence rate for mental
illness is about 21 %. The figure was derived by synthesizing two major studies
indicating that within a 1-year period this percentage of the adult population has a
diagnosable mental disorder based on “reliable, established criteria.” Based on 2010
census figures, this means that over 45 million individuals are affected. Moreover,
the Surgeon General indicates that almost half these individuals – 9 % of US adults –
experience some significant functional impairment. A subpopulation of 5.4 % of
adults has a “serious” mental illness that interferes with some area of social
functioning.
Most distressingly, none of these huge figures included even the approximately
20 % of children and adolescents estimated to have mental disorders with at least
mild functional impairment, or the 5–9 % who suffer “serious emotional distur-
bance.” Adults 55 and older are another subpopulation. Though not as extensively
documented, the Surgeon General cites figures indicating that almost 20 % have
some diagnosable mental disorder during a 1-year period, and that almost 4 % have a
serious mental illness.
Various reports from the World Health Organization (WHO) demonstrate that
mental health problems in the USA are mirrored in other countries, often in an
extreme form because there is less help available. Here are some of the findings:

• Mental, neurological, and behavioral disorders are common to all countries and
cause immense suffering. People with these disorders are often subjected to social
isolation, poor quality of life, and increased mortality. These disorders are the
cause of staggering economic and social costs. That is, because mental disorders
often strike early, their total economic cost to society is almost as large as all other
illnesses combined.
• Hundreds of millions of people worldwide are affected by mental, behavioral,
neurological, and substance use disorders. For example, estimates made by WHO
in 2002 showed that 154 million people globally suffer from depression and
25 million people from schizophrenia; 91 million people are affected by alcohol
use disorders and 15 million by drug use disorders. A recently published WHO
report shows that 50 million people suffer from epilepsy and 24 million from
Alzheimer and other dementias.
• In addition to the above figures, many other disorders affect the nervous system or
produce neurological sequelae. Projections based on a WHO study show that
worldwide in 2005, 326 million people suffered from migraine; 61 million from
cerebrovascular diseases; 18 million from nervous system infections or neuro-
logical sequelae of infections. The number of people with neurological sequelae
of nutritional disorders and neuropathies (352 million) and neurological sequelae
secondary to injuries (170 million) also add substantially to the above burden.
Uncounted are the large number of people who suffer from chronic pain. In the
USA alone it is estimated that at least 100 million Americans suffer from a
chronic pain condition.
• About 877,000 people die by suicide every year. In at least two thirds of these
cases, a treatable mental illness is deemed to be causal.
Preface to the Second Edition vii

• One in four patients visiting a health service has at least one mental, neurological,
or behavioral disorder, but most of these disorders are neither diagnosed nor
treated.
• Mental illnesses affect and are affected by chronic conditions such as cancer,
heart and cardiovascular diseases, diabetes, and HIV/AIDS. Untreated, they bring
about unhealthy behavior, noncompliance with prescribed medical regimens,
diminished immune functioning, and poor prognosis. Some common disorders,
such as lung cancer, are the consequence of mental disorders (in this case,
nicotine addiction).
• Cost-effective treatments exist for most disorders and, if correctly applied, could
enable most of those affected to become functioning members of society.
• Barriers to effective treatment of mental illness and substance use disorders
include lack of recognition of the seriousness of mental illness and lack of
understanding about the benefits of services. Policy makers, insurance compa-
nies, health and labor policies, and the public at large – all discriminate between
physical and mental problems.
• Most middle- and low-income countries devote less than 1 % of their health
expenditure to mental health. There are as many as 200 times more psychiatric
workers in high-income as opposed to low-income countries. Consequently
mental and behavioral health policies, legislation, community care facilities,
and treatments for people with mental illness are not given the priority they
deserve.
• War and other disasters have a major influence on mental health and psychosocial
well-being. Rates of mental health disorder tend to double after emergencies.

Early support for the ideas underlying this project came through letters
expressing clear understanding and encouragement from the Society for Neuro-
science (the President and the Chair of the Education Committee), the Federation
of European Neuroscience Societies (FENS), the Japanese Neuroscience Society,
the Indian Academy of Neuroscience, from UNESCO, from the International
Brain Research Organization (IBRO, whose regional offices will assist with
dissemination of the text), from the Director of the Earth Institute, Jeffrey
D. Sachs (Professor of Sustainable Development, Columbia University), from
the American expert on education Professor Howard Gardner (Harvard Univer-
sity), and from the Chinese Academy of Sciences (three members are among our
editors).
Insofar as professors in developing countries want to use this text as part of their
efforts to launch neuroscience programs, they might want to see the Appendix by
Richard Brown (Dalhousie University, Canada), a paper that gives tips about
developing such programs. In addition, a few authors have supplied videos to let
students in developing countries know how these authors became interested in
neuroscience and to give an idea of what their laboratories look like.
Finally, we consider this large volume to comprise a “feeder text” for other, more
detailed treatments such as those edited by Eric Kandel et al. (Principles of Neural
Science, 5th edition, McGraw-Hill), Larry Squire et al. (Fundamental Neuroscience,
viii Preface to the Second Edition

3rd edition, Elsevier), and Dale Purves et al. (Neuroscience, 4th edition, Sinauer). At
spots in the current text, we have referred to specific chapters in one or more of these
texts in order to make up for any potential deficit.
We gratefully acknowledge financial support for the first edition from three
foundations: the Nour, Moos, and New York NeuroScience Foundations and from
Pfizer, Inc. All authors and editors agreed to do their work without compensation.
This entire project benefitted from the wise counsel and foresight of the Neurosci-
ence editor at Springer, Ann Avouris. With a high level of skill, Ann has encouraged
and guided this project from its inception to its completion. Special thanks to the
International Brain Research Organization (Pierre Magistretti and Sten Grillner,
Secretary-Generals) for assisting the free international distribution of this text, in
electronic form, to universities in developing countries.

New York, NY, USA Donald W. Pfaff

Rockville, MD, USA Nora D. Volkow
Preface to the First Edition

The primary purpose of this project has been to produce a comprehensive, electronic
introduction to current-day neuroscience in a didactic form useful for upper level
premedical students, entering medical students, and graduate students in a wide
variety of countries. The Supervisory Editors and the authors, in their international
distribution, reflect our intention to recognize the growing interest in neuroscience
and expertise in neuroscientific research across the world.

Neuroscience Addresses Medical and Public Health Problems

Worldwide

Neuroscience research provides basic discoveries about how the brain works and
about how the brain controls behavior. These discoveries are then applied for the
good of humankind. Neuroscience, broadly defined, also offers pivotal components of
both medical education and the delivery of medical services. For example, depression
and schizophrenia – once viewed as purely “behavioral” problems – are now candi-
dates for neurochemical/neuropharmacological treatments. Degenerative conditions
such as neurosyphilis, HIV-associated dementia, and Alzheimer’s can now be delayed
by science-based treatments. Coma and persistent vegetative state are approached by
manipulating brain mechanisms responsible for arousal. Indeed, as neuroscience
explores the etiology of disease – the complex interplay between biological, psycho-
logical, and sociocultural factors – it is increasingly valuable in understanding an array
of diseases. A recent report by the Surgeon General, in the United States, cites several
such diseases: schizophrenia, bipolar disorder, early onset depression, autism, atten-
tion deficit/hyperactivity disorder, anorexia nervosa, substance abuse disorders, and
panic disorder, among many others.
The Surgeon General states that in the USA, the 1-year prevalence rate for mental
illness is about 21 %. The figure was derived by synthesizing two major studies
indicating that within a 1-year period this percentage of the adult population has a
diagnosable mental disorder based on “reliable, established criteria.” Based on
2010 census figures, this means that over 45 million individuals are affected.
Moreover, the Surgeon General indicates that almost half these individuals – 9 %
of US adults – experience some significant functional impairment. A subpopulation

ix
x Preface to the First Edition

of 5.4 % of adults have a “serious” mental illness that interferes with some area of
social functioning.
Most distressingly, none of these huge figures even included the approximately
20 % of children and adolescents estimated to have mental disorders with at least
mild functional impairment, or the 5–9 % who suffer “serious emotional distur-
bance.” Adults aged 55 years and older are another subpopulation. Though not as
extensively documented, the Surgeon General cites figures indicating that almost
20 % have some diagnosable mental disorder during a 1-year period and that almost
4 % have a serious mental illness.
Various reports from the World Health Organization (WHO) demonstrate that
mental health problems in the USA are mirrored in other countries, often in an
extreme form because there is less help available. Here are some of the findings:

• Mental, neurological, and behavioral disorders are common to all countries and
cause immense suffering. People with these disorders are often subjected to social
isolation, poor quality of life, and increased mortality. These disorders are the
cause of staggering economic and social costs. That is, because mental disorders
often strike early, their total economic cost to society is almost as large as all other
illnesses combined.
• Hundreds of millions of people worldwide are affected by mental, behavioral,
neurological, and substance abuse disorders. For example, estimates made by
WHO in 2002 showed that 154 million people globally suffer from depression
and 25 million people from schizophrenia; 91 million people are affected by
alcohol abuse disorders and 15 million by drug abuse disorders. A recently
published WHO report shows that 50 million people suffer from epilepsy and
24 million from Alzheimer and other dementias.
• In addition to the above figures, many other disorders affect the nervous system or
produce neurological sequelae. Projections based on a WHO study show that
worldwide in 2005, 326 million people suffered from migraine, 61 million from
cerebrovascular diseases, and 18 million from nervous system infections or
neurological sequelae of infections. The number of people with neurological
sequelae of nutritional disorders and neuropathies (352 million) and neurological
sequelae secondary to injuries (170 million) also add substantially to the above
burden. Uncounted are the large number of people who suffer from chronic pain.
• About 877,000 people die every year by committing suicide. In at least two thirds
of these cases, a treatable mental illness is deemed to be causal.
• One in four patients visiting a health service has at least one mental, neurological,
or behavioral disorder, but most of these disorders are neither diagnosed nor
treated.
• Mental illnesses affect and are affected by chronic conditions such as cancer,
heart, and cardiovascular diseases; diabetes, and HIV/AIDS. Untreated, they
bring about unhealthy behavior, noncompliance with prescribed medical regi-
mens, diminished immune functioning, and poor prognosis. Some common
disorders, such as lung cancer, are the consequences of mental disorders (in this
case, nicotine addiction).
Preface to the First Edition xi

• Cost-effective treatments exist for most disorders and, if correctly applied, could
enable most of those affected to become functioning members of society.
• Barriers to effective treatment of mental illness and substance abuse disorders
include lack of recognition of the seriousness of mental illness and lack of
understanding about the benefits of services. Policy makers, insurance compa-
nies, health and labor policies, and the public at large – all discriminate between
physical and mental problems.
• Most middle- and low-income countries devote less than 1 % of their health
expenditure to mental health. There are as many as 200 times more psychiatric
workers in high- as opposed to low-income countries. Consequently, mental and
behavioral health policies, legislation, community care facilities, and treatments
for people with mental illness are not given the priority they deserve.
• War and other disasters have a major influence on mental health and psychosocial
well-being. Rates of mental health disorder tend to double after emergencies.

Further Reading

In addition to our text, we recommend the following.

For material on the molecular events that occasion the development of primitive
cells into neurons, we recommend the writings by Ali Hemmati-Brivanlou; for
information regarding the genetic guidance of neuronal developmental processes,
we recommend to consult papers by Marc Tessier-Lavigne and by Sarah Guthrie.
Also, see Part VIII in the Kandel text referenced below, chapters by Thomas Jessell
and Joshua Sanes, and the several chapters on CNS development in the Squire text,
mentioned below.
For comprehensive coverage of the visceral motor system, students can consult
the Purves text, referenced above, Chap. 21.
For more coverage of mechanisms of reward, please consult the Squire et al. text,
Chap. 43.
For systematic coverage of attention, please see the Squire text, referenced above,
Chap. 48. For a treatment of the mechanisms underlying language, please consult the
Kandel text, Chap. 60, and the Purves text, Chap. 27.
Treatments of addictive disorders in other texts include Chap. 49 in the Kandel
text, referenced above, and Chap. 42 in the Squire et al. text.
Early support for the ideas underlying this project came through letters expressing
clear understanding and encouragement from the Society for Neuroscience (the
President, and the Chair of the Education Committee), the Federation of European
Neuroscience Societies (FENS), the Japanese Neuroscience Society, the Indian
Academy of Neuroscience, from UNESCO, from the International Brain Research
Organization (IBRO, whose regional offices will assist with dissemination of the
text), from the Director of the Earth Institute, Jeffrey D. Sachs (Professor of
Sustainable Development, Columbia University), from the American expert on
education Professor Howard Gardner (Harvard University), and from the Chinese
Academy of Sciences (three Members are among our Editors).
xii Preface to the First Edition

Insofar as professors in developing countries want to use this text as part of their
efforts to launch neuroscience programs, they might want to see the Appendix by
Richard Brown (Dalhousie University, Canada), a paper that gives tips about
developing such programs. In addition, a few authors have supplied videos to let
students in developing countries know how these authors became interested in
neuroscience and to give an idea of what their laboratories look like.
Finally, I consider this large volume to comprise a “feeder text” for other, more
detailed treatments such as those edited by Eric Kandel et al. (“Principles of Neural
Science”, 5th edition, McGraw-Hill), Larry Squire et al. (“Fundamental Neurosci-
ence”, 3rd edition, Elsevier), and Dale Purves et al. (“Neuroscience”, 4th edition,
Sinauer). At spots in the current text where I feel bereft, I have referred to specific
chapters in one or more of these texts in order to make up for the deficit.
I gratefully acknowledge financial support from the Nour, Moos, and New York
NeuroScience Foundations and from Pfizer, Inc. All authors and editors agreed to do
their work without compensation. This entire project benefitted from the wise
counsel and foresight of the Neuroscience editor at Springer, Ann Avouris. With a
high level of skill, Ann has encouraged and guided this project from its inception to
its completion. Special thanks to the International Brain Research Organization
(Pierre Magistretti, Secretary-General) for assisting the free international distribution
of this text, in electronic form, to universities in developing countries.

New York, NY Donald W. Pfaff

About this Book

Section 1: Basic Neuroscience

Biophysics

The capacity of the neurosciences to absorb and use information from the physical
sciences is increasing every year, with the techniques of the physical sciences adding
to the rigor and depth of current neuroscientific work. In some of the chapters below,
we have had to pick examples from complex fields, as the numbers of topics (e.g.,
potassium channels) are too large to cover individually. Our authors are experts. For
example, Roger Papke has described unique properties of certain nicotinic acetyl-
choline receptors; and Ramon Latorre, based in Chile, has demonstrated how
specific protein domains sense stimuli and open pores, and is also a member of the
US National Academy of Sciences.

Development

Molecular and genetic approaches are most easily applied to development of the
nervous system. We expect this area of neuroscience to continue to grow explo-
sively. We are missing material on the molecular events that occasion the develop-
ment of primitive cells into neurons, for which you should try to find writings by Ali
Hemmati-Brivanlou; and we are underpowered regarding the genetic guidance of
neuronal developmental processes, for which you should consult papers by Marc
Tessier-Lavigne and by Sarah Guthrie. Also, see Part VIII in the Kandel text
referenced above, chapters by Thomas Jessell and Joshua Sane; and the several
chapters on CNS development in the Squire text, mentioned above.

Cell Biology of Neurons and Glia

Two of the most unique features of the central nervous system are the arrangement of
neuronal processes in space (neuroanatomy) and the presence of electrically excitable
cells (biophysics). Rather than trying to subsume an entire text of neuroanatomy, we

xiii
xiv About this Book

have emphasized those aspects of neuroanatomy, which essentially comprise subjects

in the field of cell biology. Among our authors, Anthony Brown is an axonal transport
expert, Roberto Araya has demonstrated that dendritic spines can act as electrical
compartments, and Helmut Kettenmann has taken leadership positions in European
Neuroscience. Rae Silver and her team discovered mast cells in the brain, while Robert
Dantzer is a leading scholar in psychoneuroimmunology.

Sensory Systems (Neuroanatomy and Physiology)

Two modalities of sensory signaling are given extra attention here: vision, because of
its plentiful and strong history of work; and pain, because of its prevalence in clinical
settings. Pain is treated here as a “basic neuroscience” subject, but clearly is also
important for the clinical topics below. Ji-Sheng Han, Chinese Academy of Sciences,
is a world-renowned expert in the regulation of pain. Christine Petit is Professor,
College de France and Institut Pasteur, French Academy of Sciences, and is a world
leader in sensory disorders and hearing molecular physiology and pathophysiology,
having won the 2006 Louis-Jeantet Prize for Medicine.
Katherine Cullen is William Dawson Chair in Neurophysiology, McGill Univer-
sity, and an Associate Editor for the Journal of Neurophysiology. And a world leader
in taste physiology, Linda Bartoshuk, is a member of the US National Academy of
Sciences and past-president of the Association for Chemoreception Sciences and of
the Association for Psychological Science.

Motor Control

Starting with the work of the great, Nobel Prize winning physiologist Sir Charles
Sherrington, the nervous system’s control over muscle contraction has provided the
most fundamental analyses of CNS function. The cerebellum and basal ganglia are
so important that they are treated at two different levels. Among our authors, Robert
Burke and Elzbieta Jankowska have world-wide reputations for their superb contri-
butions to the neurophysiology of motor control.

Neurophysiology of Other, Specific CNS Regions and Networks

Among the topics that fall outside straightforward sensory and motor functions, we
have included the following. Among our authors, Larry Swanson is widely recog-
nized as a foremost neuroanatomist, Ruud Buijs has done the most to put forebrain
nerve cell biology in the context of whole-body physiological requirements, while
Morten Kringelbach is a widely admired forebrain neuroanatomist. Greg Funk has
contributed to our understanding of glutamatergic signaling for central respiratory
control and is the Triennial Gold Medal Recipient, Physiological Society of
New Zealand, for outstanding contributions to physiological research.
About this Book xv

Network Analyses in Mammalian Brains

Behavioral neuroscience has progressed from the consideration of “centers” to the

realization that particular nerve cell groups are “nodes” in extensive networks
devoted to individual functions.

Neurochemistry, Neuropharmacology

There is an amazing variety of chemical reactions specific to the nervous system that
are crucial for regulating CNS performance. The aim in the following chapters is to:
(a) state some general principles; and (b) give specific examples (e.g., the hypotha-
lamic nonapeptides and opioid peptides). Lakshmi Devi and Lloyd Fricker cover the
basic topics in a systematic and didactic fashion, appropriate for medical students
and graduate students. The expert in brain energy supplies, Pierre Magistretti, has
become Secretary-General of the International Brain Research Organization (IBRO).

Brain Energetics

A necessary condition for the maintenance of a normal membrane potential and the
firing of action potentials is the metabolic support of nerve cells. Both the supply of
metabolites and the disposal of “waste” are considered.

Neuroendocrinology

Several chapters will cover the brain’s control over pituitary hormones and, in turn,
hormone effects on brain and behavior. Marc Freeman’s long and strong career on
hypothalamic control of the pituitary is widely admired. Cheryl Sisk has made
multiple discoveries in the timing of hormone effects on the brain during develop-
ment, while Joel Elmquist is a world leader in the analysis of the brain’s regulation of
feeding. We lack a comprehensive chapter about the visceral motor system, for
which students can consult the Purves text, referenced above, Chap. 21.

Regulation of Natural Behaviors

Far from covering all the natural behaviors that might be considered, we have
included only a few, large domains of behavioral states that have received intense
study with respect to their mechanisms. Gert Holstege (Groningen) has made
breakthrough discoveries about brain activity during emotional excitement, while
Ron de Kloet (Leiden) and Marian Joels (Utrecht) are world leaders in neurochem-
ical mechanisms related to stress. Ralph Adolphs has combined sophisticated neu-
roanatomy with discriminating experimental design in the analysis of how the
xvi About this Book

amygdala regulates social behaviors in humans. For more coverage of mechanisms

of reward, please consult the Squire et al. text, Chap. 43.

Cognitive Neuroscience

Studies of cognitive functions and learned behaviors involve the types of mecha-
nisms covered above and, in addition, involve regulated changes in CNS perfor-
mance according to the environment and schedules of reinforcement. Richard Morris
is perhaps the best known contributor to methodologies for studying learning,
notably the “Morris Water Maze,” while Paul Luiten and his team have shown
progressive deterioration of brain microvessels during aging. We lack systematic
coverage of attention; please see the Squire text, referenced above, Chap. 48. And for
a treatment of mechanisms underlying language, please consult the Kandel text,
Chap. 60, and the Purves text, Chap. 27.

Emerging Experimental Techniques in Neuroscience: Genetics

The genetic revolution has changed every single area of biology, and in the case of
neuroscience it has provided new tools to understand how the brain develops and is
organized as well as how genes contribute to brain diseases. In parallel, our under-
standing of the regulatory mechanisms that coordinate gene expression (epigenetics
and epigenomics) have provided a means for investigating neuronal differentiation
and to assess the influence of environmental factor on brain function. Additionally,
genetics has led to the development of methodological tools that allow researchers to
manipulate specific cell types and circuits (chemogenetics and optogenetics).

Emerging Experimental Techniques in Neuroscience: Imaging

Technologies for imaging the living brain have advanced and diversified enor-
mously. In this section, we restrict discussion to optical imaging in that they are
one of the most powerful tools for investigating neuronal and neurocircuitry activity
in rodents with potential applications in other animal models. In humans, two
modalities PET and MRI have transformed our ability to study the human brain
and have accelerated our understanding of brain diseases.

Emerging Experimental Techniques in Neuroscience: Computational

Neuroscience

Neuroscientists are able to take advantage, increasingly, of new techniques based on

physical, chemical, and computational sciences. We provide just a sample of
them here.
About this Book xvii

Section 2: Clinical Neuroscience

Developmental Disorders

While not aiming to be a complete neurology text, it is important to provide some

ideas about the applications of modern neurobiology to clinical syndromes of great
importance. Three criteria influenced our choices of topics: (i) that the disorder has
some estimable degree of prevalence; (ii) that it relates to an interesting area of
neuroscience; and (iii) that we can cover it better than in other texts. As mentioned
above, genetic modifications that cause brain pathologies are most sensitively
detected in the cases of developmental disorders. Among our authors, Merlin
Butler’s work led to the discovery of genomic imprinting as the cause of Prader-
Willi syndrome. Catherine Barthélémy has an international reputation for her work
as a clinician dealing with children having autism spectrum disorders.

Systems Disorders

Damage or dysfunction of networks in the brain can have severe consequences on

behavior. We include some prevalent forms of system disorders. Among our authors,
Michal Schwartz has made discoveries concerning the role of immune cells in
ameliorating effects of spinal cord damage; while Steven Laureys and his team
have made startling observations about brain activity in vegetative state patients.

Pain

Four topics on pain are included in the basic neuroscience section, above. Three
essentially important clinical subjects are treated here. John Brust has, literally,
“written the book” on headache, while Richard Bodnar has made career-long
contributions on the neurophysiology and neurochemistry of pain suppression.

Neuroimmune Disorders

Some neural/immune interactions have disastrous consequences. Socrates Tzartos

has determined the pathogenic role of autoantibodies against the main immunogenic
region of the acetylcholine receptor in myasthenia gravis. Beyond frank
neuroimmune diseases, we are missing chapters on chronic fatigue syndromes and
on neurotoxicology, but we do cover well the fact that neural tissue dysfunction can
sometimes be attributed to microbial causes (Kristensson chapter).

Addictive Disorders

Addictions pose tremendous threats to public health and can impact entire commu-
nities. Addiction to heroin is discussed above, in the chapter on opioid peptides.
xviii About this Book

Treatments of addictive disorders in other texts include Chap. 49 in the Kandel text,
referenced above, and Chap. 42 in the Squire et al. text.

Degenerative Diseases

Progressive deterioration of the nervous system can impair many systems concur-
rently. These diseases are distinct from developmental disorders and infectious
diseases. Kay Double has contributed novel insights into the vulnerability of the
degenerating neurons in Parkinson’s disease, while John Finberg is a co-inventor of
the Parkinson medication rasagiline. Aldrin Molero and Mark Mehler’s demonstra-
tion of Huntington’s-related alterations in the development of striatal cells suggest
novel mechanistic links between development and aging in the brain.

Gender Identity

Sexual differentiation of the human brain is treated here in both its basic neuroen-
docrine (above) and its clinical aspects. Dick Swaab’s team in Amsterdam has led
world neuroendocrinology in analyzing hormone-dependent and gender-dependent
neuroanatomical and histochemical features of the human brain.

Other Psychiatric Disorders

The World Health Organization charts the large number of people disabled by
various psychiatric disorders. These disorders are, in some cases, closely linked to
the basic science chapters involving regulation of natural behavior. Missing is a
chapter on anxiety; please consult Chap. 48 in Kandel et al. Helen Mayberg and her
team have made a startling rate of progress in linking human anterior cortex neuronal
activity to depression. Andreas Meyer-Lindenberg, working both at NIH in Betheda,
Maryland, and in Germany, has made breakthroughs in identifying brain mecha-
nisms of risk factors for schizophrenia.
Editors

Editors-in-Chief

Donald W. Pfaff Laboratory of Neurobiology and Behavior, The Rockefeller

University, New York, NY, USA
Nora D. Volkow National Institute on Drug Abuse (NIDA), National Institutes of
Health (NIH), Rockville, MD, USA

Managing Editor

Diany Paola Calderon Pfaff Laboratory, The Rockefeller University, New York,
NY, USA

xix
Supervisory Editors

Andrea Ballabio Naples, Italy

Professor of Medical Genetics; Director, Telethon Institute of Genetics and Medi-
cine; Past President of the European Society of Human Genetics
Expertise: genetic diseases of CNS

Francisco Bezanilla Chile and Chicago, USA

Professor, University of Chicago; Member, National Academy of Sciences; Presi-
dent of the Biophysical Society
Expertise: ions, channels voltage sensors

Pierre Chambon Illkirch, Strasbourg, France

Founder and Director of the Institute for Genetics and Cellular and Molecular Biology
in Strasbourg. He has received the Louisa Gross Horwitz Prize from Columbia
University in 1999 and the Albert Lasker Award for Basic Medical Research in 2004.
Expertise: molecular biology

B. N. Dhawan Lucknow, India

Professor, University of Lucknow; Former Director, Central Drug Research Insti-
tute; Former President, Indian Academy of Neurosciences. Experience with
UNESCO, WHO, UNIDO, and Commonwealth Science Council
Expertise: autonomic nervous systems

Richard Faull Auckland, New Zealand

Professor of Anatomy, University of Auckland School of Medicine; awarded the
Rutherford Medal in 2007 by the Royal Society of New Zealand for outstanding
contributions to science.
Expertise: neurodegenerative diseases

Eberhard Fuchs Göttingen, Germany

Professor of Neurobiology, Medical School, University of Goettingen; Coordinator
of the EU Consortium on effects of early stress, 2002 Science Award from the
Stifterverband der Deutschen Wissenschaft; Founder and CEO of ENCEPHARM
Expertise: behavioral neurobiology

xxi
xxii Supervisory Editors

Detlev Ganten Berlin, Germany

Founding Director, Max Delbrück Center for Molecular Medicine, Berlin-Buch,
1992–2004; Advisor to German government Minister for Science; Chief Executive
Officer, Charité-University Medicine Berlin, 2004–2008; now: Charité Foundation,
Chairman of the Foundation Board; Max Planck Award (Germany), Okamoto Award
(Japan), Ciba Award (USA); Member, LEOPOLDINA, National Academy of Sciences
Expertise: neuropharmacology

Jisheng Han Beijing, China

Director of the Neuroscience Institute, Beijing Medical University; Member, Chi-
nese Academy of Sciences
Expertise: pain

Tomas Hokfelt Stockholm, Sweden

Professor, the Karolinska Institute; Codiscoverer of the major monoaminergic sys-
tems of the mammalian brain
Expertise: neuroanatomy

Nancy Ip Kowloon, Hong Kong, China

Chair of Biochemistry, Hong Kong University; Member, Chinese Academy of Sciences
Expertise: trophic factors

Tadashi Isa Myodaiji, Okazaki, Japan

Professor at the National Institute for Physiological Sciences, Myodaiji, Okazaki;
Chair of Japan Neuroscience 2009; 2006 Tsukahara Nakaakira Memorial Award
from the Brain Science Foundation
Expertise: motor control and recovery of neural function

Reinhard Jahn Göttingen, Germany

Professor and Director, Department of Neurobiology, Max Planck Institute for
Biophysical Chemistry, Goettingen
Expertise: molecular regulation of synaptic functions

E. Barry Keverne Cambridge, UK

Professor, University of Cambridge; Director, Sub-Department of Animal Behavior;
Fellow of the Royal Society; Fellow of the Academy of Medical Sciences and
Foreign Honorary Member of the American Academy of Arts and Science
Expertise: ethology, and genetic imprinting

Stephen Laureys Liège, Belgium

Professor of Neurology, University of Liege Medical School; Director, Coma Sci-
ence Group; 2004 ASSC William James Prize; 2006 Van Geen Award for Belgian
Nuclear Research; 2006 Mind Science Foundation Award
Expertise: neurology
Supervisory Editors xxiii

Andrew Lumsden London, UK

Professor of Developmental Neurobiology and Director, MRC Centre for Develop-
mental Neurobiology, King’s College, London; Fellow of the Royal Society
Expertise: developmental and molecular neuroscience

Michael Le Moal Bordeaux, France

Chief, INSERM Unit on Pathophysiology of Behavior, University of Bordeaux;
Member, Academie Francais
Expertise: neurochemistry

Andreas Meyer-Lindenberg Mannheim, Germany

Director of Germany’s Central Institute of Mental Health, Mannheim; Professor of
Psychiatry and Psychotherapy at the University of Heidelberg; ACNP Elkes Award,
Bennett Award of the Society for Biological Psychiatry, the Nature Medicine Prize
for Translational Neuroscience and the Kurt Schneider Prize, NARSAD Distin-
guished Investigator; Member, LEOPOLDINA – German National Academy of
Science
Expertise: genetic influences on behavior

Till Roenneberg Munich, Germany

Head of the Department of Medical Psychology, Ludwig-Maximilians-University,
Munich, and Director of the Neuroscience Course; Coordinator of European
research networks on chronobiology
Expertise: chronobiology, circadian rhythms

Yasuo Sakuma Tokyo, Japan

Professor and Chair of Physiology, Nippon Medical School, Tokyo; Editor-in-Chief,
Journal of Physiological Sciences
Expertise: neurophysiology

Mriganka Sur Cambridge, Massachusetts, USA

Head, Department of Brain and Cognitive Sciences, and Newton Professor of
Neuroscience, MIT; Fellow, American Academy of Arts and Sciences; Fellow of
the Royal Society
Expertise: developmental neuroscience

Dick F. Swaab Amsterdam, Netherlands

Professor of Neurobiology, University of Amsterdam; Former Director, Netherlands
Brain Research Institute, Founder and Former Director, Netherlands Brain Bank,
Royal Honours, granted 1998; Lifetime Achievement Award for Alzheimer’s Dis-
ease Research, 2002; Royal Netherlands Academy Medal for achievement in Neu-
roscience, 2008
Expertise: neurobiology of neuropsychiatric disorders
xxiv Supervisory Editors

Ryosuke Takahashi Kyoto, Japan

Chair, Department of Neurology, University of Kyoto School of Medicine
Expertise: degenerative diseases

XiongLi Yang Shanghai, China

Former Dean of Life Sciences, Fudan University; Member, Chinese Academy of
Sciences
Expertise: vision
Contents

Volume 1

Section I Basic Neuroscience

Part I Biophysics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

1 Water, Ions, Membranes, Pumps, and Transporters . . . . . . . . . . . 3

Roger L. Papke
2 Voltage-Gated Ion Channels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Lori Isom, Gustavo Patino, Luis Lopez-Santiago, and Yukun Yuan
3 Ionotropic Glutamate Receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Rolf Sprengel
4 Signal Transduction-Dependent Channels . . . . . . . . . . . . . . . . . . . 85
Ramon Latorre, Carlos González, and Patricio Rojas
5 Post-Synaptic Potentials and Action Potentials: Membrane
Potentials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
Stewart Hendry

Part II Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137

6 Basics of Stem Cell Biology as Applied to the Brain ........... 139

Inna Tabansky and Joel N.H. Stern
7 Neural Stem Cells in Cerebral Cortex Development ........... 157
Felipe Mora-Bermúdez, Miguel Turrero García, and
Wieland B. Huttner
8 Adult Neurogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
Gerd Kempermann
9 Axonal Guidance: Making Connections . . . . . . . . . . . . . . . . . . . . . 201
Peter Kozulin and Linda J. Richards

xxv
xxvi Contents

10 Dendritic Elaboration: Morphology and Chemistry ........... 225

Astrid Rollenhagen and Joachim H.R. Lübke
11 Regressive Phenomena: Refining Connections . . . . . . . . . . . . . . . . 265
Will Agnew-Svoboda, Alex L. Kolodkin, and Martin M. Riccomagno

Part III Cell Biology of Neurons and Glia .................... 295

12 Dendritic Morphology and Function ....................... 297

Roberto Araya
13 Axonal Transport . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333
Anthony Brown
14 Cell Biology of the Synapse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381
Rochelle S. Cohen
15 Molecular Regulation of Synaptic Release . . . . . . . . . . . . . . . . . . . 423
Reinhard Jahn and Janina Boyken
16 The Postsynaptic Density ................................ 475
Rochelle S. Cohen
17 Gap Junctions and Electric Synapses . . . . . . . . . . . . . . . . . . . . . . . 511
Rolf Dermietzel and David C. Spray
18 Glial Cells: Neuroglia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 547
Helmut Kettenmann and Alex Verkhratsky
19 Immune System Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 579
Katherine Nautiyal
20 Neuroimmune Signaling: Cytokines and the Central
Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 601
Rachel H. Kennedy and Rae Silver
21 Psychoneuroimmune Phenomena: Neuroimmune Interactions . . . 643
Robert Dantzer and Keith W. Kelley

Volume 2

Part IV Sensory Systems (Neuroanatomy and Physiology) . . . . . . 671

22 Retina: Neuroanatomy and Physiology . . . . . . . . . . . . . . . . . . . . . 673

Andreas Reichenbach and Andreas Bringmann
23 The Superior Colliculus and Visual Thalamus . . . . . . . . . . . . . . . . 747
Barry E. Stein, Terrence R. Stanford, Dwayne W. Godwin, and
John G. McHaffie
Another random document with
no related content on Scribd:
The Project Gutenberg eBook of The Christmas
Bishop
This ebook is for the use of anyone anywhere in the United States
and most other parts of the world at no cost and with almost no
restrictions whatsoever. You may copy it, give it away or re-use it
under the terms of the Project Gutenberg License included with this
ebook or online at www.gutenberg.org. If you are not located in the
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you are located before using this eBook.

Title: The Christmas Bishop

Author: Winifred Margaretta Kirkland

Illustrator: Louise G. Morrison

Release date: July 23, 2022 [eBook #68590]

Language: English

Original publication: United States: Small, Maynard and Company,

1913

Credits: Charlene Taylor and the Online Distributed Proofreading

Team at https://www.pgdp.net (This file was produced from
images generously made available by The Internet
Archive/American Libraries.)

*** START OF THE PROJECT GUTENBERG EBOOK THE

CHRISTMAS BISHOP ***
THE CHRISTMAS BISHOP
Sometimes, against the dark faces of the housefronts, window
shades were rolled up, like eyelids opening, on home-pictures
that reminded the Bishop it was Christmas night
See page 140
 The Christmas Bishop
BY

WINIFRED KIRKLAND
Author of “Introducing Corinna,” “The Home-Comers,” etc.

ILLUSTRATED BY

LOUISE G. MORRISON

BOSTON
SMALL, MAYNARD AND COMPANY
PUBLISHERS
 Copyright, 1913
By SMALL, MAYNARD AND COMPANY
(Incorporated)

THE VAIL-BALLOU CO.,

Binghamton, N. Y.
THE CHRISTMAS BISHOP
 PART I
Christmas morning, blue-black, pricked with stars against the
Bishop’s window panes. Westbury lay asleep beside its curving river,
the great old houses with gardens that ran terraced to the bank, the
churches, the college, even the new teeming tenements at the
bending of the water, all lay asleep in the Christmas dawning. The
Bishop alone was awake, and against the darkness before his eyes
pictures raced. He had been a poet once, so long ago that when
sometimes they sang his hymns in church he had forgotten they
were his, but he still kept the poet’s trick of thinking in pictures during
those strangely alert moments between sleep and full awakening.
The pictures fell into the march of a poem.
It was a storied city built upon two hills cleft by a valley. On the
twin crests towered great palaces and a temple. Where the hills sank
toward the north, there were terraced streets and narrow climbing
byways. There were markets and booths and all the signs of
multitudinous life, but throughout all the place one heard no sound,
saw nothing that moved, yet one knew that the whole city throbbed
with the pulse-beats of innumerable homes. A gray pall hung low, as
if the abrupt Oriental dawn had been arrested; the gray dimmed the
marble of the palaces, and dulled the temple gold. In the silent gloom
one waited.
One did not know whence he had come, the Child who was
suddenly there, in the streets of that city without stars, a sacred city
once; but wherever he knocked upon the portal, quickly all within
woke to life, and became a teeming, bustling household; again,
when he withdrew, all was once more silence and darkness.
He was a tiny child, barefoot and pale, some little lost waif from
the mountains who had come seeking his kinsfolk among the homes.
So fast he pattered over the pavement that his pale hair and his
white tunic streamed upon the wind. His little yearning hands
stretched out showed fair as a baby’s in that wintry twilight. Ever and
again he knocked and entered, and always, entering, his face flamed
with hope, and always, coming forth, he was sobbing, for he found
no welcome.
On and on he went, while each black street along which he hurried
was stabbed ever and again by the opening and shutting of a ruddy
door. In the silence one heard it plain, the heavy sound of a door that
closed because it did not know him. At length he had passed the city
portals and was mounting the hill-slope that is Golgotha, a form all
pale upon the dark, blown hair and robe and pattering feet. There the
Child turned, for it seemed he was the little Prince of that city, and all
the folk his kin. Rising a-tiptoe he stretched out his hands, cross-
wise, to them in love, and suddenly the sun, withheld, leaped kingly
above the hills beyond Jordan, and the silent air was full of wings
and of voices, the chant of the Christmas angels singing home the
Homeless One, and in that flood of light and song all that city knew
the Child they had lost their own, forever.
Slowly, before the Bishop’s eyes, that gold radiance dimmed into
the bleak gray twilight that was stealing over his room. Sharp as life
shall strike at visions came a sound from below that struck the
dreamy smile from his lips, leaving a twitching pain; certain sounds
had that power of intolerable renewal. A homely enough sound,
merely the thud of a lid dropped upon a flour bin, but it seemed now
to be a flour bin in a doll-house pantry in their first Rectory, his and
Annie’s. He would seek her there before going out to his parish calls.
She would be standing with her back to him, hands deep in dough,
and would turn to him her cheek, olive that always went rose
beneath his kiss. He could still hear the catch of her breath as she
whispered good-by, for Annie, deeply joyous, had yet always treated
joy a little apprehensively, as if knowing it would not last so very
long. Looking back over many years, the Bishop thought how young
Annie had been when she died, and Nan had been younger still.
Nan! There it was again! That flash of hot pain through his head,
followed by a numbing dullness, even stranger to bear. He had felt
this several times of late. The Bishop ran a hand over his forehead.
He seemed to be floating far, without thought, yet this was not sleep.
Slowly, slowly, he drew back, but his thoughts were heavy, not clear.
He seemed to lie there waiting, waiting for something. Surely thus he
had always waited on Christmas morning. He listened. It would come
in a moment. There! A scurry along the hall, the clatter of the door-
handle, a rush, a jump, curls, lips, bubbling chuckles, little cold toes
to be warmed in his hand! Hear the shouts and the singing of her,
feel the pummelling of her little hands!
“Christmas! Christmas! Christmas!” shrilling straight up to the
angels! Was she not Christmas joy turned mad, his little girl!
He was full awake now. His lips formed a word. We are very weary
of old pain repeated when we whisper out to God like that.
The Bishop wondered why people say that one grows used to
loss, and that old age grows dull in feeling. Still he had got used to it,
of course. This was Christmas, too; it was quite natural that he
should feel it more on Christmas. He must be a little patient then with
himself about it, perhaps, on Christmas. Yet when had there been a
day when he had not missed them, his own!
The Bishop turned toward the eastward window, and on his gray
and beautiful face fell the gray and beautiful morning, for the Bishop
was one who had made God a habit, so that he turned to Him
instinctively without thinking about it at all. And since also he was a
man of quick visual imagination he thought of God quite simply: he
saw Him standing there, between the bed and the brightening
window, in the form of a young Jewish rabbi. He always stood there,
to greet the Bishop’s day. Together they always went about, step
matching step, so that the Bishop was never a lonely man. To
himself he always thought of the Nazarene as the Friend, because,
so he thought, it was by loneliness that Jesus had learned how to
love. Since the Bishop always thought in words and in pictures, it
seemed to him that the Friend said to him now, “Rise. Let us go forth
into the morning. It is Christmas. It is the day of giving.”
While he dressed, the Bishop still knew God standing there, but
felt rather than seen, being lost sometimes in mist and dizziness.
The spaces in the room were strange; it was a very long journey to
the washstand, and the white window squares seemed to advance
and then recede. The Bishop could see his brush plainly enough on
the bureau scarf, but it was a long time before he could make his
hand reach it. He had to smile quaintly at himself at last, for he was
sitting on the bed mechanically counting the flower baskets in the
worn Brussels carpet, flower baskets that ran diagonally to the chair
holding his coat. Groping a little, the Bishop achieved the coat, then
stood trembling. Undoubtedly he was ill that morning, but Mrs.
Graham should not know it! For he must go out, he must go to
church, there was no service in all the year so dear to him as the
Christmas communion at St. John’s. He would force his blurring
head to go through with it, and Mrs. Graham should not keep him in!
Keep him in! A frown twitched on his forehead, an old man’s
helplessness at the thought of coddling. Why should a woman he
had known but three years be so solicitous over his health, dictating
about his rubbers and his socks—he was not ill, nor was he so very
old! At that his brow cleared in a sunny flash of amusement, for of
course, he was very old, eighty-one, and besides Mrs. Graham was
very good to him. Still to-day she must not keep him at home, for to
stand once more within the rail offering the chalice to his people had
become a deep and blind desire, overmastering all sense of
weakness. Besides, there were other matters and grave ones to be
seen to, to-day. Somehow—he looked toward the eastward window
—the strength would come for the day, as it always came.
Slowly, while he stood looking out into the morning grown rosy
now with the coming sun, his head cleared more and more, as he
thought about his Westbury as it brightened beneath the Christmas
sunrise. Few towns, the Bishop thought, had changed so little in sixty
years. He looked out on the same Westbury he had first seen when
he had come to St. John’s college as a boy. Stately old River Street
with its twin rows of elms still curved to the curve of the river. Each
quiet old house had in the rear a terraced wintry garden sloping to
the wide and sparkling water. The Bishop knew each of these
houses, even as far as Lucy Hollister’s, which was beyond his sight.
Lucy still kept the house of her girlhood where the Bishop had first
known her, known Lucy and her cousin, Annie. Far beyond Lucy’s
house, River Street changed to towering tenements and grimed
factories, the place of the strangers, where the Bishop often walked,
but wistful and puzzled, for it was this part of Westbury alone that
had changed since his boyhood, although even then it had been the
place of work-people, for whom St. John’s Southside Mission had
been founded. The Bishop stood thinking of the mission.
Well in sight, breaking the row of houses set among their wintry
trees, sprang the spire of St. John’s, and beyond its Rectory lay the
brown, cube-like buildings of the college above the sweeping river, a
small college of mighty men. It was there that the Bishop and his
roommate, Barty Judd, had learned to dream dreams. It was the
glory of Westbury, the kindly old city, remote, unworldly, that it had
set so many young men dreaming. The Bishop smiled to think how
proudly Westbury still pointed to its seven bishops, for the spirit of
Westbury had not changed in all the sixty years since the founding of
the mission. Westbury had given the Bishop, he thought, the most
beautiful thing in his life; it was this that brought the light to his face
as he thought of the gift he wished to give Westbury in return, to-day,
if—if he could! At that “if” his eyes deepened with a sharp and subtle
change, then cleared as the passing thought of the day before him
yielded to memories, and he saw the afternoon of the laying of the
mission corner-stone. As they had walked home together, the
Bishop, after long silence, had broken into boyish fire of words,
seeing all his life before him. Lucy had listened and answered, but
Annie had been silent.
Dreamer as the boy had been, he had never dreamed of coming
back one day, long afterwards, and living to be an old, old man in the
bishop’s house in Westbury.
The sun was climbing to a golden blaze now, filling with hope the
day before the Bishop. He was always a good deal of a child in his
Christmas feeling. There was work before him on this Christmas day,
in his own house and out of it. Quite simply he closed his eyes a
moment, with bowed head, thinking of the Westbury he loved and of
three within it, whom he should see that day.
The Bishop’s tall figure swayed a little as he grasped the stair rail,
and for an instant his gaze was vague upon the dusky hall, upon the
gloomy wall-paper, the threadbare carpet. It was a gray and worn old
house in which the Bishop’s soul was harbored. A succession of
housekeepers, under the oversight of Mrs. Hollister, kept it in order,
but it needs the authority of kinship to change a wall-paper or a
carpet. Thus it was that the Bishop’s long hallway was hardly more
his own than the pavement outside, or his own dining-room door
before which he paused, hardly more his own than the doors along
his familiar River Street. His hand lingered on the knob, for, thinking
of Mrs. Graham within, and of the testing now of his three years’
hope, he had grown apprehensive and wistful. Then his face flashed
firm in a smile, as he looked toward Someone beside him there in
the dim hall. That little way of looking toward the Friend with a quick
upward smile was one of the Bishop’s habits engendered by
solitude. He never meant to betray his thought publicly, yet
sometimes wayfarers in the train, on the street, were startled at the
sudden passing of strange light across the gray face, making it, as
now in the opening doorway, the face of a little child. The Bishop
bent toward the black-clad little woman before him the bow that
belonged to the days of his youth. Age had stooped his shoulders,
but never stiffened their grace, nor that of the sweep of his extended
hand. His face—lean, clear-chiselled, blue-eyed, and heavily
thatched with white—was ashine with Christmas greeting.
“I wish you a beautiful Christmas!” he said.
Mrs. Graham’s glance met the Bishop’s furtively. She had restless
brown eyes beneath a tranquil parting of brown hair, curling and
lightly silvered. Her mouth looked as if locked upon discontent. She
was a stout, rosy little woman who moved in a heavy, bustling
manner. She put her hand into the Bishop’s awkwardly, never having
become accustomed to one who shook hands as a morning
greeting.
“Merry Christmas,” she murmured perfunctorily, as, in the holiday
absence of a maid, she turned toward the business of the Bishop’s
breakfast. The raised slide of the dumb-waiter made a gap in the
solid paneling of dark cupboards occupying one wall. Like other
dining-rooms on River Street, the room had two long windows
looking toward the water. There was a wide piazza beyond them,
hung with the gnarly ropes of leafless Virginia creeper. It was a dark-
wainscoted room, but now the level eastern sun flooded it, and there
was a great crimson spot of roses at the Bishop’s plate. The table
was set for one, he noticed; when Maria was away, Mrs. Graham
insisted on serving him with her own hands, instead of settling
comfortably into her usual seat. In the silent room, only the sound of
the dumb waiter that creaked and rattled, but the Bishop was waiting
to speak, after the long patience of three years. When his breakfast
had been set forth to her satisfaction, Mrs. Graham sank upon the
edge of a chair near the window, keeping an alert eye on the
Bishop’s needs, but having also an air of absence.
“Well,” she burst out at last, “so it’s Christmas again!”
“Yes,” the Bishop smiled, “‘again.’ It comes around pretty often,
doesn’t it? This is your third Christmas in Westbury.”
“I wonder how many more I’ll have, in Westbury.”
“Is it such a bad place to spend Christmas in then, Westbury?”
“Bad for me, yes! After Fair Orchard!”
“But I had hoped you had begun to feel at home in Westbury.”
“Me! At home! In Westbury! No, I’ve no place here and never can
have. I see that plain enough,—just a housekeeper, anyway! I’ve no
place in the place, I mean, like at home! Oh, there’s no harm in
Westbury! It’s not as bad as some towns. There’s show here, but it’s
not showy; there’s money, but there’s manners, too! Only there’s no
heart in the place! How could there be, with Dr. Newbold running the
church and Mrs. Hollister running society?”
“They both have hearts, I am sure, Mrs. Graham.”
“Maybe. Not for plain people, or poor people, though. Maybe for
you. Although Dr. Newbold—” she broke off sharply, teeth on lip,
while her eyes, too full and bright with meaning, changed before the
Bishop’s gaze, and she altered her unspoken sentence, concluding,
“Dr. Newbold suits the place all right. He don’t suit me, that’s all. It’s
kind of spoiled church for me, going to St. John’s, and church in Fair
Orchard was such a lot to me. It’s queer when you always hear
about Westbury being such a strong church place that it should have
spoiled church for me. It’s all right when you preach, of course,
Bishop, but it’s something else I’m talking about. It was different at
home—oh,” her rosy face darkened savagely, “sometimes it seems
as if my church was just another of the things she’s taken from me
along with my home and my boy!”
The Bishop closed his eyes an instant, seeking counsel.
“It’s Christmas that upsets me so! Christmas that brings it all back
on me so. And then to-day she sent, Florence herself, she sent the
baby’s picture on a post-card. It’s signed ‘From Florence.’ You’d think
after all that’s happened, she’d have let Dan send it, the first word
I’ve had from either of them for three years!”
She rose and filled the coffee cup abruptly. “Well,” she jerked the
words out, “Christmas and other days, I’ve got to grin and bear it,
being turned out by my son’s wife. But it’s been worse since there
was a baby.”
“It’s the baby’s first Christmas,” mused the Bishop.
“Yes, he’s seven months and sixteen days old.”
The Bishop smiled up at her, “May I see him? Where is the
picture?”
She laid it before him. The Bishop adjusted his glasses, then
removed them to look from the picture to a keen scrutiny of the
grandmother’s face.
“Yes,” she answered his look. “You see it then? The baby looks
like us, like Dan and me. And I can see Dan’s father in him, too.
There’s not a hair of him that looks like the Reynoldses,—that lot!”
The Bishop was examining the photograph minutely. Mrs. Graham
looked over his shoulder, but at his next word she moved away
again. “That’s his mother’s hand holding him, isn’t it, that shadow
under his arm?”
“Yes! His mother’s hand! He looks like us, but he don’t belong to
us! He’s hers!”
 The Bishop glanced up, “And I suppose he’s also the other
grandmother’s.”
“No! Florence has no mother. I’m all the grandmother that baby’s
got!”
“I think you never told me that before,” he paused thoughtfully,
then looking over to her standing by the window, he said, feeling
slowly for words, “So the baby’s mother, that girl out at Fair-Orchard,
has had no mother—to go with her—on that way—a woman goes, to
bring home, a little child?”
The Bishop’s voice was soft with the awe of many years ago. The
grandmother flushed, muttering, “She would not have wanted me.
She had Dan.”
The Bishop’s eyelids had fallen, quivering, over his eyes. He was
far away; again he watched with Annie, with Nan, as he said, “But
men cannot understand. God does not mean them to. Such things
are a secret between God and women, like the coming of Mary’s
little child. Each mother needs a mother then. It was not—it was not
till then that I understood how much my Nan had lost when she lost
her mother.”
“It did not live, did it, at all, your daughter’s child?” whispered Mrs.
Graham.
The Bishop shook his head, not speaking, thinking of the little
waxen loveliness they had laid to sleep with Nan in the hollow of her
arm. His lips showed their rare palsied trembling, murmuring, “Both
together, Nan and the little one. She had been so well! I was not
prepared—” the eyelids of his quiet gray face trembled, then opened
on the blue eyes, as he said, “Of course, we know they do not die.
They are alive, somewhere where the dreams come true that we
dream for our children.” He smiled into her eyes, “For we are great
old dreamers, aren’t we, we grandparents?” He raised his hand from
the chair-arm, as if it would have pleaded, “But I think each mother
needs the grandmother to help her dream. I think she is wanting you
now, that Florence out there.”