Beyond Neurotransmission - P. Katz (Oxford, 1999) WW

406 Pages·1999·23.35 MB·English

Beyond Neurotransmission

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Beyond Neurotransmission

Neuromodulation and its Importance for Information Processing

Edited by

Paul S. Katz

Department of Biology
Georgia State University

OXFORD
UNIVERSITY PRESS

Oxford University Press, Great Clarendon Street, Oxford OX2 6DP
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© Oxford University Press, 1999

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A catalogue record for this book is available from the British Library

Library of Congress Cataloging in Publication Data
Beyond neurotransmission : neuromodulation and its importance for
information processing / edited by Paul S. Katz.
Includes bibliographical references and index.
1. Neural transmission - Regulation. I. Katz, Paul S.
[DNLM: 1. Neurotransmitters - physiology. 2. Neurons - physiology.
3. Mental Processes - physiology.
QV 126B573 1999]
QP364.5.B49
1999
573.8'54 - dc21
DNLM/DLC
for Library of Congress
98-39256
CIP

ISBN 0 19 852424 2

Typeset by Technical Typesetting Ireland in Belfast
Printed in Great Britain by Bookcraft Ltd., Midsomer Norton, Avon

Foreword

by Ronald M. Harris-Warrick

It wasn't very long ago that most neuroscientists thought the brain was a
black and white world: all chemical communication in the nervous system
was mediated by either rapid excitatory or rapid inhibitory synaptic poten-
tials, and the major role of neurons was to algebraically summate synaptic
input and decide whether or not to spike. That time is now gone, as this fine
introduction to neuromodulation makes abundantly clear. We now know
that there is a huge diversity of non-traditional modes of neuronal communi-
cation, grouped under the general name of neuromodulation, which creates a
multicolored rainbow of varied ways for neurons to be affected and to affect
one another.
Paul Katz, one of the most innovative leaders in this field, has selected an
international group of experts to bring together a superb summary of the
cutting edge of research spanning the full range of this growing and exciting
field, from biochemical mechanisms of receptors and second messengers to
behavioral analyses of neuromodulation during learning. Since neuromodula-
tion is ubiquitous and affects every part of nervous system function, neurosci-
entists of all stripes can benefit from reading this book; it should provoke
new research in a number of areas. Scientists studying molecular and cellular
aspects of nervous system function will deepen their understanding of the
complexities of molecular modulation. Systems neuroscientists working at
higher levels will also see how neuromodulation permeates their field: it is no
longer possible to discuss sensory processing or motor coordination without
a full recognition of the many roles that non-traditional forms of neuronal
activity and communication play. Behavioral pharmacologists who work
with neuromodulators such as amines and peptides will recognize that the
terms 'excitatory' and 'inhibitory' only hint at the complex functions that
compound such as dopamine and serotonin play in affecting higher level
functions. Even high-level modelers and neurophilosophers will find useful
reminders of the fractal nature of the real nervous system in which each
neuron is an independent microprocessor, with variable baseline states and
variable non-linear input/output functions that are controlled by the modu-
latory milieu. For all of us who study the brain, the moment-to-moment
plasticity of properties of neurons and their connections is central to all
higher order cognitive function, and cannot be ignored.
By giving an accessible yet thorough survey of the field of modulation,
Katz and his colleagues are showing all of us a better view of the machinery
of the real brain. The reader should be prepared to accept a quantum leap in
their perception of the complexity of neural function. Thanks to the actions
of neuromodulators, the number of possible interactions and states of activity

vi Foreword

in the brain is inconceivably greater than was previously thought. This
revelation is delightful and exciting, and gives us a glimmer of understanding
into how magnificent human brains could have created Hamlet and The Art
of the Fugue.

Preface

As neuroscientists, our goal is to understand how nervous systems process
information. What steps occur in the brain during decision making? How do
animals perceive their environment? How do animals learn? One problem
that we face is that we don't know all of the forms that information takes in
the nervous system, nor how it is communicated. Often there is an underlying
assumption that information is transferred through the nervous system in the
form of neurotransmission consisting of fast excitatory postsynaptic poten-
tials (EPSPs) and fast inhibitory postsynaptic potentials (IPSPs); all other
neuronal actions, such as neuromodulation, are usually considered secondary
and not really involved in active information transfer. This view of informa-
tion flow dismisses what may be some of the brain's most important
computational capabilities.
The aim of this book is to explore these other mechanisms of transferring
information through the nervous system. The title of this book, Beyond
Neurotransmission, is not meant to imply that we already understand all the
implications of neurotransmission. In fact, it can be said that we may be
misled by the apparent simplicity of neurotransmission. Rather, the point
that we are making is that there are many other forms of neuronal communi-
cation that also need to be considered when trying to understand how
nervous systems process information.
Although the term neuromodulation has been in common usage for more
than 20 years, there is still a great deal of disagreement about what it means,
as I found when I conducted an informal survey of my colleagues working in
the field. I asked them to label particular situations as either:

A) Neurotransmission,
B) Neuromodulation,
C) Neither,
D) Both, or
E) Cannot be determined from this information.

Here are the responses that I received from three of the situations:

Situation 1) Slow EPSPs such as peptidergic, muscarinic, or aminergic input
to sympathetic ganglia.

Responses:
33% of the respondents said it was an example of neurotransmission because
the inputs caused a depolarization,
33% said it was neuromodulation because these inputs have slow actions,
and
33% said it was both neurotransmission and neuromodulation.

viii
Preface

Situation 2) A morphologically defined synapse that uses G protein-coupled
receptors (i.e. metabotropic receptors).

Responses:
25% of the respondents said that this would be considered neurotransmis-
sion because it was a morphologically defined synapse,
25% said neuromodulation because anything with a metabotropic receptor is
modulatory,
25% said it was both neurotransmission and neuromodulation, and
25% said that it can't be determined from this information.

Situation 3) Presynaptic inhibition (e.g. GABA inputs onto axonal terminals).

Responses:
40% said neurotransmission because it involves morphologically defined
synapses and ionotropic receptors and
60% said this would be neuromodulation because the presynaptic inhibition
alters the strengths of synapses.

This informal poll convinced me that the book needed to begin by addressing
what neuromodulation is. It is of little use to again attempt to strictly define
neuromodulation or coin new terms. This just leads to more disagreements
over semantics. The important point here is that, regardless of what we call
them, there are more modes for communication of information in the
nervous system. In this case, neuromodulation is as good a term as any.
This book seeks to examine neuromodulation and its functional role in
information flow and neural circuit flexibility. It has three functional divi-
sions:

1. The first section of the book deals with the mechanisms of neuromodula-
tion. It is intended to provide a basis for systems physiologists to catch up
with some of the latest cellular concepts in neuromodulation. It takes a
large volume of current literature and synthesizes some fundamental
principles for neuromodulation and cellular signaling.

•
Chapter 1 begins by exploring some of the alternate forms of neuronal
communication and why they are important for understanding how the
brain works.
•
Chapter 2 discusses the roles that intercellular messengers play in both
neurotransmission and neuromodulation. It defines how neurons commu-
nicate information and the roles that neurotransmitters and receptors play
in defining the message.
•
Chapter 3 reviews our current knowledge of intracellular second messen-
ger processes involved in neuromodulation. This is a review of how
modulatory signals are translated into cellular actions.

Preface
ix

•
Chapter 4 examines how neurons change their behavior in response to
neuromodulatory signals. The control of neuronal properties is what
really defines neuromodulatory communication.
•
Chapter 5 discusses the concept of metaplasticity where plasticity itself
can be altered. This chapter offers a slightly different perspective on the
importance of heterosynaptic versus homosynaptic mechanisms in the
control of synaptic plasticity.

2. In order to understand the roles played by neuromodulation in vivo., it is
necessary to look at how systems of neurons use neuromodulation to
process information. Therefore, the second section of the book focuses on
the use and control of neuromodulation. These chapters provide useful
examples from many different systems. They serve to illustrate the impor-
tance of neuromodulatory signaling in information flow in the nervous
system. I hope these chapters will also inspire systems physiologists to
consider how neuromodulation might be operating in their own experi-
mental systems.

•
Beginning with information entering the nervous system, Chapter 6 ex-
plores how neuromodulation affects sensory processing. It shows that
neuromodulation has effects at every stage of sensory processing.
•
Chapter 7 looks at the output of the nervous system by examining how
neuromodulation alters neuromuscular transmission and what role that
alteration plays in the production of muscular movements. This chapter
also gives a more general look at the role that neuromodulation plays in
matching input/output properties of senders and receivers.
•
Chapter 8 examines how neuromodulation enables the nervous system to
generate different patterns of activity which are translated into move-
ments. Here the actions of neuromodulators on the basic mechanisms of
motor pattern generation are shown to enable neuronal circuits to pro-
duce flexible outputs.
•
Neuromodulation also plays many important roles in learning, memory,
and attention, as is discussed in Chapter 9. This chapter is important
because it stresses the need for mechanisms that go beyond long-term
potentiation (LTP) in models of associative learning.

3. Finally, the last section of the book deals with the next level of complex-
ity, modulation of modulation or metamodulation. Chapter 10 investi-
gates the various ways that neuromodulation itself is controlled. I feel that
this is the next direction for work in the field.

To answer questions about information processing in the nervous system,
researchers begin by asking how individual systems of neurons operate to
produce particular forms of behavior. For example, one may study how the
neurons in the abdominal nerve cord in a crayfish communicate with each