Spinal Cord Plasticity: Alterations in Reflex Function

242 Pages·2001·4.75 MB·English

by  Richard F. Thompson (auth.)

SPINAL CORD PLASTICITY
Alterations in Reflex Function
SPINAL CORD PLASTICITY
Alterations in Reflex Function
edited by
Michael M. Patterson
Nava Sautheastern University
James W. Grau
Texas A & M University
SPRINGER SCIENCE+BUSlNESS MEDIA, LLC
Library of Congress Cataloging-in-Publication Data
Spinal cord plasticity: alterations in reflex function/ edited by Michael M. Patterson,
James W. Grau.
p.;cm.
lncludes bibliographical references and index.
ISBN 978-1-4613-5553-3 ISBN 978-1-4615-1437-4 (eBook)
DOI 10.1007/978-1-4615-1437-4
l. Spinal cord. 2. Neuroplasticity. 3. Reflexes. 1. Patterson, Michael M. Il. Grau,
JamesW.
[DNLM: l. Spinal Cord-physiology. 2. Neuronal Plasticity-physiology. 3.
Reflex-physiology. 4. Spinal Cord Injuries-rehabilitation. WL 400 S7583 2001]
QP371 .S645 2001
612.8'3---dc21
2001038130
Copyright © 2001 Springer Science+Business Media New York
Originally published by Kluwer Academic Publishers in 2001
Softcover reprint of the hardcover 1s t edition 2001
AII rights reserved. No part of this publication may be reproduced, stored in a
retrieval system or transmitted in any form or by any means, mechanical, photo
copying, recording, or otherwise, without the prior written permission of the
publisher, Springer Science+Business Media, LLC .
Printed on acid-free paper.
T ABLE OF CONTENTS
Foreword VB
1 Spinal Plasticity
Richard F. Thompson
2 Pavlovian and Instrumental Conditioning Within the Spinal Cord:
Methodological Issues
James W. Grau and Robin L. Joynes 13
3 Pavlovian Conditioning of Flexion Reflex Potentiation in
Spinal Cat: Temporal Effects Following Spinal Transection
Russell G. Durkovic 55
4 Spinal Fixation: Long-term Alterations in Spinal Reflex
Excitability With Altered or Sustained Sensory Inputs
Michael M. Patterson 77
5 Spinal Cord Plasticity in the Acquisition of a Simple Motor Skill
Jonathan R. Wolpaw 101
6 Mechanisms of Central Sensitization of Nociceptive
Dorsal Horn Neurons
William D. Willis, Jr. 127
7 Noxious Stimulus-Induced Plasticity in Spinal Cord Dorsal Horn:
Evidence and Insights on Mechanisms Obtained Using the Formalin
Test
Terence 1. Coderre 163
8 Neural Darwinism in the Mammalian Spinal Cord
v. Reggie Edgerton, Roland R. Roy and Ray D. de Leon 185
VI
9 Spinal Cord Plasticity Associated with Locomotor Compensation to
Peripheral Nerve Lesions in the Cat
Laurent Bouyer and Serge Rossignol 207
10 Lautband (Treadmill) Therapy in Incomplete Para-and Tetraplegia
Anton Wemig, Andras Nanassy and Sabina MUller 225
Index 241
Foreword
The area of spinal cord plasticity has become a very actively researched field. The
spinal cord has long been known to organize reflex patterns and serve as the major
transmission pathway for sensory and motor nerve impulses. However, the role of
the spinal cord in information processing and in experience driven alterations is
generally not recognized. With recent advances in neural recording techniques,
behavioral technologies and neural tracing and imaging methods has come the
ability to better assess the role of the spinal cord in behavioral control and
alteration. The discoveries in recent years have been revolutionary. Alterations due
to nociceptive inputs, simple learning paradigms and repetitive inputs have now
been documented and their mechanisms are being elucidated.
These findings have important clinical implications. The development of
pathological pain after a spinal cord injury likely depends on the sensitization of
neurons within the spinal cord. The capacity of the spinal cord to change as a
function of experience, and adapt to new environmental relations, also affects the
recovery locomotive function after a spinal cord injury. Mechanisms within the
spinal cord can support stepping and the capacity for this behavior depends on
behavioral training. By taking advantage of the plasticity inherent within the spinal
cord, rehabilitative procedures may foster the recovery of function.
The chapters in this book explore some of these recent advances in spinal
cord plasticity. The authors characterize spinal cord plasticity from both a
behavioral and molecular perspective and describe how behavioral and
pharmacological treatments can foster the recovery of function after a spinal cord
injury.
The book is the outgrowth of a symposium organized by the editors and
Reggie Edgerton, Jonathan Wolpaw and William Willis. The symposium was held
at the UCLA Tennis Center in conjunction with the Society for Neuroscience
Meetings on November 7, 1998. The organizers wish to thank the sponsors of the
symposium for their support and for the use of the UCLA facilities. The program
was sponsored by the Parke-Davis division of Warner-Lambert, the Kent Waldrep
Foundation, the Wadsworth Center (Albany), and the Department of Physiological
Science, the Neural Repair Program and the Brain Research Institute at UCLA. A
special thanks goes to Linda Maninger in helping to organize the facilities for the
symposium at UCLA.
We also want to thank Brenda Riepenhof for her work on the preparation
of the fmal manuscripts of the book chapters. Our thanks also to Stephanie
Washburn at Texas A and M and Stephanie Elkins at UCLA for their most gracious
help during the editing process. Our appreciation goes to Michael Williams and
Mary Panarelli for their continuing and unwavering help in the publishing process.
Michael M. Patterson
James W. Grau
1 SPINAL PLASTICITY
Richard F. Thompson
Neuroscience Program
University of Southern California
University Park
Los Angeles, CA 90089-2520
"Traditional views often held that little learning occurs within the spinal cord,
however, recent findings suggest that neurons within the spinal cord are highly
plastic" (Organizers' statement for the symposium).
1.1 SPINAL HABITUATION
One aspect of spinal plasticity with a long history is habituation of spinal reflexes.
Sherrington (1906) studied this phenomenon at length in the spinal dog. He used the
term fatigue but was careful to define it only as the response decrement to repeated
stimulation. Indeed, in ingenious experiments he ruled out sensory adaptation and
muscle fatigue as contributing factors and presented strong evidence from reflex
interaction studies that the final common path, the spinal motor neurons were not
themselves fatigued.
In a series of studies by the author and William Alden Spencer, we
characterized the processes of habituation and sensitization in detail at both
behavioral and neuronal levels (Thompson and Spencer, 1966). We used habituation
and sensitization of the hindlimb flexion reflex in the spinal animal (cat) as a model
system to explore the neuronal mechanisms underlying this form of behavioral
plasticity, often now termed non-associative learning. Kandel and associates
completed similar studies on mechanisms of habituation and sensitization in a
2 Richard F. Thompson
monosynaptic pathway in the marine mollusk Ap/ysia (Carew, Pinsker and Kandel,
1972; Kandel, 1976), as we also did using a monosynaptic pathway in the isolated
frog spinal cord (Farel and Thompson, 1976; Fare!, Glanzman and Thompson,
1973). A primary goal in all these studies was to understand the mechanisms of
these forms of behavioral plasticity at the neuronal/synaptic/ molecular levels.
Rather than review these now "historical" studies in any detail I summarize
here the results of our analytic studies on localization and identification of the
process of plasticity in the mammalian spinal cord. A schematic of the spinal cord is
shown in Figure 1.1, together with the experimental manipulations used. The
repeated stimulus was to skin (Ss) or cutaneous nerve (Sin) and the behavioral
response was contraction of a flexor muscle (Rm), recording of the ventral root
response (Rn) or intracellular recording from the alpha motor neurons (MRa).
~~,r~ ,n} 'nr~·~.w «f~;f"i-1 ~({t
k9
Figure 1.1. Much simplified schematic of the mammalian spinal cord indicating some of the
experimental procedures used to study plasticity (habituation, sensitization and classical conditioning).
Electrical stimuli can be delivered to skin (Ss, b), to afferent nerves (Sin, cutaneous nerve; S2N, muscle
afferent nerve; x, dorsal root) or to cutaneous nerve terminals for antidromic activation (T). Responses
can be recorded from a flexor muscle (Rm), a motor nerve (Rn), the ventral root (Y), intracellularly from
the motor neurons (MRa) or antidromically from the mixed or cutaneous nerve (Rs). See text for more
details. (From Thompson, 1967).
Spinal Cord Plasticity 3
Since both skin (Ss) and sensory nerve stimulation (Sin) yielded identical
habituation, sensory adaptation was ruled out. Since both muscle contraction (Rm)
and ventral root response (Rn) showed identical habituation, muscle fatigue was
ruled out. The possibility that motor neuron excitability decreased with repeated
stimulation was evaluated by interpolated stimulation of a muscle nerve (S2N)
activating the monosynaptic Ia afferent to motor neuron response. This
monosynaptic response, recorded either from the ventral root (Rm) or intracellularly
from the motor neuron (MRa), did not change at all over the course of habituation.
Similarly, spike generation threshold to intracellular stimulation via the intracellular
electrode (MRa) did not change during habituation. The possibility that alterations
in cutaneous afferent terminal excitability, e.g., presynaptic inhibition (at T in
Figure 1.1) was tested by interpolated stimulation of the afferent terminals at T with
antidromic recording of the dorsal root response at Rs. This antidromic dorsal root
response did not change at all over the course of habituation to repeated skin or
cutaneous nerve stimulation, thus ruling out changes in terminal excitability.
Sensitization in this system was induced by strong cutaneous stimulation
elsewhere on the leg (see Figure 1.1). This strong extra stimulation caused an
increase in the habituated response, and in the control response to cutaneous
stimulation before habitation training. Unlike habituation, sensitization resulted in a
significant increase in excitability in motor neurons. Thus, following the sensitizing
stimulus there was a significant increase the monosynaptic muscle nerve-motor
neuron response.
These experiments localized the process of habituation to spinal
interneurons and suggested that interneurons played a key role in both habituation
and sensitization.
In studies with Philip Groves, recording from spinal interneurons during
habituation and sensitization, we identified several classes of interneurons,
including one class that showed only decrements to repeated stimulation,
independent of reflex sensitization and another class that showed dramatic increases
in response during sensitization. Thus led us to the "dual process" theory of
habituation (Groves and Thompson, 1970).
The basic idea is that repeated stimulation resulted in synaptic processes of
decrement and increment and the two processes interact to yield the behavioral
outcome. This is schematized in oversimplified terms in Figure 1.1, where the
decremental process would occur in the interneurons between cutaneous afferents
and alpha motor neurons (shown as a single interneuron in Figure 1.1), whereas the
process of sensitization resulted in a build-up of excitation in an interneuron pool (?
in Figure 1.1), leading to increased excitability of the motor neuron at a. We were
able to account for a wide range of behavioral (and neuronal) phenomena of
habituation and sensitization with this theory. In monosynaptic systems, where
appropriate analysis is possible, e.g., Aplysia and isolated frog spinal cord,
habituation is a presynaptic process apparently involving a decrease in probability
of transmitter release as a result of repeated stimulation.
4 Richard F. Thompson
1.2 SPINAL CONDITIONING
Unlike habituation, the early history of spinal conditioning -- the possibility that
classical or instrumental training procedures could induce associative learning -like
phenomena in the spinal cord --was somewhat controversial. Pavlov's dictum to the
effect that associative learning required the cerebral cortex did not help matters.
Shurrager, working in Culler's laboratory (where so many pioneering
studies of brain substrates of learning and memory were carried out), published the
first modem studies of classical conditioning of spinal reflexes, (Shurrager and
Culler, 1940; 1941). In brief, they used acute spinal dogs, measured the twitch
response of a partially dissected flexor muscle, gave paw shock as a US and weak
stimulation of the tail as CS. They obtained robust acquisition in about half their
animals and demonstrated CS alone extinction and successively more rapid
reacquisition in repeated training and extinction sessions. Unfortunately, adequate
controls for sensitization and pseudoconditioning were not run in these studies.
A few years later Kellogg and associates reported negative results in
attempts at spinal conditioning (e.g., Kellogg, 1947; Kellogg et. aI., 1946; Deese
and Kellogg, 1949). They used chronic spinal dogs and the flexor response of the
whole leg. The US was shock to the paw of that leg and the CS was a shock to the
opposite hind paw. Kellogg's choice ofCS locus was unfortunate. Paw shock elicits
a crossed extension reflex that would work against the development of a
conditioned flexion response. Pinto and Bromiley (1950) completed an extensive
spinal conditioning study with long-term acute spinal animals and found only
inconclusive evidence because of passive hindquarter movements caused by
anterior limb movements.
The bible in the field at that time (Morgan and Stellar, Physiological
Psychology, 2nd ed., 1950) drew the following conclusion:
"So there is a good deal wrong with the experiments as they stand.
They do not let us conclude confidently that spinal conditioning can take
place. We need more experimenting before we can be sure. In fact, it may
turn out that what seemed to be conditioning is more correctly called reflex
sensitization, as Kellogg has suggested above. Even if that is the case the
experiments will be of some value, for knowing as little as we do about
conditioning, it is possible that conditioning may be closely related to reflex
sensitization." (p.446)
This conclusion apparently discouraged others from pursuing the phenomena
of spinal conditioning for many years to come.
In 1967 the author and a graduate student took up the gauntlet (Fitzgerald
and Thompson, 1967). We used acute spinal cats, detached the distal tendon of left
hind limb flexor muscle (tibialis anterior) led it out through a small skin incision
and attached it to a force-displacement transducer to measure the flexor responses.
The CS was a weak shock to thigh skin and the US was a brief strong shock to the
left hind paw, CS and US coterminating. All animals were first given four UCS
alone trials following by a series of CS alone trials to establish a control response
level. Half the animals were then given paired CS-US trials and half were given