Download studying the isolated central nervous system

Comp. Biochem. Physiol. Vol. 93A,No. 1, pp. 9-24, 1989
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STUDYING THE ISOLATED CENTRAL NERVOUS
SYSTEM; A REPORT ON 35 YEARS: MORE
INQUISITIVE THAN ACQUISITIVE
G. A. KERKUT
Department of Neurophysiology, Southampton University, Southampton, SO9 3TU, UK.
Telephone: (0703) 594341
(Received 13 May 1988)
Al~ract--1. The CNS from invertebrate animals such as slugs, snails, leeches, and cockroaches, can be
isolated and kept alive for many hours.
2. The electrical and pharmacological properties of invertebrate CNS neurons have many similarities
and it is probable that the basic rules governing the CNS evolved more than 600 million years ago.
3. The nerve cells can show sodium action potentials, calcium action potentials, EPSP, IPSP, biphasic
potentials, electrogenicsodium pump potentials, and a variety of potassium, sodium, calcium and chloride
currents.
4. Invertebrate CNS ganglia contain identifiable individual nerve cells whose properties and responses
to neurotransmitters and drugs are constant and repeatable from preparation to preparation.
5. It was possible to set up an isolated CNS-nerve trunk-muscle preparation and study the transport
of radioactive material from the CNS to the muscle and from muscle to CNS. This has provided
information about axoplasmic transport in both invertebrate and vertebrate preparations.
6. The methods developed from studies of invertebrate isolated CNS preparations have been applied
to vertebrate isolated CNS preparations.
7. In addition to thin slices of the mammalian brain, it is possible to keep 5 can lengths of the whole
mammalian spinal cord and brain stem alive for many hours.
8. The isolated mammalian spinal cord has functional ipsilateral and contralateral reflexes, ascending
and descending pathways, extensive sensory integrative local area networks, and inhibitory interneuron
circuits. Much of the/n vivo circuitry is functional/n vitro.
9. The isolated mammalian spinal cord and brain stem can be developed to include functional higher
brain circuits that will provide increased understanding of the control and integrative action of the
mammalian central nervous system.
INTRODUCTION
I have been lucky. I have had very supportive parents,
enthusiastic gifted teachers and co-workers, good
health, and a resonable amount of energy.
Most of my interests have developed from coming
into contact with enthusiastic teachers. When I was
at school, teaching was an honoured profession and
many of my teachers were people of outstanding
academic ability with strong personalities. The enthusiasm for their subject and their interest in teaching
had an immediate effect. They acted as powerful
catalysts and developed the talents latent in many of
their pupils. One became interested in the subject,
read around it, and in the end knew much more than
would be required by the yearly examination.
Subjects, people and places, all came to life and were
as real to me as the everyday events.
In the sixth form my main teacher, "Jasper"
Machin did not believe in formal teaching; he preferred our discussing different topics, reading around
a subject, thinking and writing essays. If I asked him
about anything he would give a brief synoptic
(Delphic) reply and suggest that I looked it up in
the well-supplied library. His normal comment was,
"You have got a brain, use it!" In this way we were
trained to work independently and think about what
we were doing.
At University I found many of the lectures very
interesting and it was also stimulating to go to other
courses and hear people such as Bertrand Russell
lecture. But the real science teaching was done at
tutorials (supervisions) where one or two students
went for one hour's instruction each week in a specific
subject with a member of the college or staff.
At that time my college did not have a specialist
in biological sciences so I could choose anyone in the
University who would teach me and I had varied
experiences. There was one rather elderly gentleman
who used to supervise in the evenings after he had
taken a good dinner. The room was warm and stuffy
and my colleague and I used to talk very quietly or
say very little, to see how long it would take for our
supervisor to fall asleep. Often we could get him to
doze off within about five minutes, though he would
later wake with a start and go on in the middle of the
sentence as if nothing had happened. In a successful
evening we could get him to fall asleep about half a
dozen times, sometimes with a good snoring accompanyment.
Another supervisor did not like reading essays and
insisted that our essays on a given topic should be no
longer than three sentences and no sentence should
contain more than thirty words.
On the other hand, there were excellent teachers
who would explain difficult subjects, set interesting
10
G . A . KERKUT
essays, and make sure that their pupils came up to the
required standard. In many cases they would also talk
about their research work and this was usually very
interesting. Enthusiasm is infectious.
In my second year at University, I asked Dr Philip
Whiting if he would supervise me and my friend. The
supervisions were held at six o'clock in the evening
and were supposed to last for an hour or fifty-five
minutes, but Philip Whiting got so interested in what
he was describing that the sessions often went on for
an hour and a half, or even two or three hours.
He was very keen that we should realize that
neurology was not based on books but on histological
specimens and would set up lots of microscope slides
so that we could gaze at Rohon-Beard cells, beautiful
Golgi preparations and methylene blue stained
neurons: all the elements of the central nervous
system in three dimensions. He introduced me to the
published works of Cajal and he matched Cajal's
illustration with microscopic preparations of similar
sections.
We were also taught other topics and in each case
had to look at the basic evidence and learn to
evaluate it. In this way I learnt that many of the
answers to important questions were not known; that
often the evidence in support of an accepted view was
not very strong; that one had to go to the original
evidence or the latest experiments to evaluate the
situation; that there were fashions in science as in
other subjects and that the fashionable explanation
was not necessarily the correct explanation.
After graduating in Natural Sciences. I stayed on
at Cambridge to carry out research on simple central
nervous systems. The simplest animal I could find
that had a well-developed central nervous system was
the starfish, Asteria rubens, and I spent three years
studying the physiology of its nervous system and the
manner in which it controlled the direction of walking
and the stepping of the tube feet. This work was done
under the expert supervision of J. E. Smith (Eric
Smith), who later became Director of the Marine
Biological Association Laboratories at Plymouth.
CNS PHYSIOLOGY
If the starfish is placed on its back and the tip of
one arm stimulated, the tube feet on that arm and on
all the other four arms would point away from the
site of stimulation, i.e. there was transmission of
specific directional information along all five arms,
and this was stopped if the radial nerve was cut. If the
cut was half-way along one of the other arms, the
direction change of pointing would take place over
the whole of the starfish up to the position of the cut,
but the tube feet beyond the cut would not point in
the new direction. The study of this phenomenon and
the stepping activity of the tube feet became the basis
for my PhD thesis.
I obtained a postdoctoral research fellowship and
decided to study the electrical activity of the molluscan central nervous system. At first, I studied Aplysia
sent to Cambridge from Plymouth but it was difficult
to obtain Aplysia throughout the year so I decided to
work on a more common molluscan species that
would allow experiments to be carried out every day,
and found that there were hundreds of slugs in my
garden. The slug brain is a very beautiful conglomerate of ganglia with nice large nerve cells and proved
to be electrically very active.
The first task was to find a suitable Ringer saline
to keep the preparation alive and during this work it
became clear that the slug CNS was very sensitive to
osmotic changes in the bathing saline and that it
could detect changes of 1% of the body fluid concentration over 4 min. Such rates of osmotic change were
found in the whole intact slug after it had been out
in the rain, or when it had been crawling on dry
surfaces. The sensitivity was similar to that of the
osmoreceptors in the mammalian brain which could
detect a 2% change in the osmotic pressure of
the blood. This work was initially carried out with
George Hughes, and then later at Southampton with
Brian Taylor.
One of the problems of working on slugs is that
there are several common species of garden slug and
its is often difficult to make a correct species
identification. For this reason, I decided that it would
be easier to work on snails. There are only two species
of Helix in England and the common species is Helix
aspersa. (The larger Roman snail, Helix pomatia, is
found mainly in the Cotswolds.) An advertisement in
the local paper offering to pay two pence for large
snails brought in offers of several hundred snails
(Helix aspersa) from small boys in the neighbourhood (Fig. 1).
I had, by this time, moved to Southampton University and helped in starting the Physiology and Biochemistry Department which later was instrumental
in the foundation of the Southampton University
Medical School.
Working in Physiology, together with Mike
Laverack, I showed that tissue extracts from the snail
had a cardio acceleratory activity in addition to that
produced by 5 HT. I was also interested in the effect
of sudden temperature changes on the nervous systems and, with Brian Taylor, showed that a sudden
increase in temperature from 20 to 23°C could cause
a temporary decrease in the spontaneous activity in
the cockroach leg nerve whilst a sudden decrease
in temperature from 30 to 25°C could cause an
temporary increase in nerve activity. The steady-state
activity after the temperature change was in the
expected direction, i.e. higher at the higher temperature and lower at the lower temperature. What
interested us were the transient changes in nerve
activity in the "wrong" direction.
The explanation for this was provided by Tony
Ridge who showed, using internal microelectrodes on
various preparations, that a sudden increase in temperature caused a hyperpolarization of the resting
potential and hence a slowing of the spontaneous
activity. Decreasing the temperature led to a depolarization of the resting potential and so a transient
increase in the rate of spontaneous activity.
We also measured the QJ0 values for changes in
membrane potential in crab, insect and frog muscle
and found that they were significantly higher than
that predicted from the Nernst equation. This suggested that the resting potential might have a
metabolic component (electrogenic metabolic pumps)
and might not be just a simple physical diffusion
potential.
Isolated central nervous systems
ll
4
Fig. 1. Some of the animals whose isolated CNS we have investigated. (1) Snail, (2) slug, (3) Tetrahymena,
(4) leech, (5) Limulus, (6) cockroach, (7) frog and (8) hamster.
SNAIL NEURONS
The large neurons in the snail brain made them
admirable subjects for intracellular recordings using
microelectrodes. Furthermore, it was relatively easy
to keep the neurons alive for many hours after the
brain had been isolated, and so study the effect of
possible neurotransmitters on nerve activity (Fig. 2).
In the 1960's it was generally thought that there
were only two neurotransmitters, acetylcholine and
noradrenaline, and that nerve cells would respond to
these. Working with Robert Walker, it quickly became apparent that the nerve cells in the Helix brain
would respond to many possible neurotransmitters
(acetylcholine, noradrenaline, glutamate, dopamine,
5HT, GABA, histamine) and that the transmitter
vocabulary of the CNS was much greater than just
two words, acetylcholine and noradrenaline,
Another interesting discovery was that the responses of the different neurons in the Helix brain
were specific to a given neuron and if we wished to
get repeatable results we had to work on identified
neurons. In this way, it became clear that some nerve
cells were stimulated by ACh whilst other nerve
cells were inhibited by ACh. Some nerve cells
responded to 5HT or dopamine or glutamate, whilst
other neurons did not respond. This started a program of work that lasted for many years mapping the
neurons in the Helix brain and determining the
response of the specific neurons to neurotransmitters
and electrical stimulation through nerve trunks. It
was also necessary to show that these neurotransmitter chemicals were present in the snail brain, and
localize them using histochemical and fluorescent
methods.
12
G.A. K/~RKUT
Fig. 2. Photograph of the suboesophageal ganglia of the isolated brain of a snail. The nerve cell bodies
are grouped in ganglia, three of which are shown in the photograph. Some of the larger neurons are
marked.
Glen Cottrell measured the levels of ACh and
5HT in the snail brain; Christine Sedden used the
Falck Hillarp method for the identification of Helix
neurons containing 5HT and dopamine and also
measured the dopamine content in the Helix brain;
Janet Loker showed that many snail neurons that
contained 5HT also responded to applied 5HT;
Charles Marsden extended the fluorescence studies
and showed the presence of a large dopamine
containing neuron in the brain of the snail Planorbis; Mary French identified the axonal pathway
in the twelve identified neurons by filling them with
Procion Yellow; and John Lambert, Rob Gayton
and Janet Loker helped bring the physiological and
pharmacological data together to make a map
of the snail brain showing the neurons that responded to glutamate, ACh, 5HT, G A B A and
dopamine.
Glen Cottrell developed this work in his laboratory
at St Andrews and, together with his co-workers,
showed that stimulation of a snail neuron containing
a known transmitter (5HT or dopamine or histamine)
could produce post-synaptic potentials in identified
follower cells, these potentials being mimicked by
local application of the specific transmitter to the
follower cell. This is probably the best evidence for
5HT, dopamine or histamine being neurotransmitters
in the central nervous system.
Electrophysiologicai studies showed that many of
the properties of Helix neurons were similar to the
properties of other animal nerve cells (Fig. 3).
EP5P
C_
IP~'P - 20ms
t
2"--Oms I
20s
Fig. 3. Types of electrical potentials that can be found in
neurons in the snail CNS. (A) The intracellular recordings
show spontaneous excitatory post-synaptic potentials
(EPSP), action potential (AP) and inhibitory post-synaptic
potentials (IPSP). (B) The preparation shows biphasic
potentials; the arrows indicate a depolarization and a hyperpolarization, one following the other. Repeated stimulation
can lead to an increase in one phase and a diminution of the
other phase, so altering the synaptie efficacy. (C) Inhibition
of long duration (ILl)) can be seen in some preparations
following stimulation of specific inputs. The inhibition can
last from 3 see up to 1 hr.
Isolated central nervous systems
INHIBITORY POST-SYNAirrlC POTENTIALS
The IPSP in snail neurons, for example, was
rapidly reversed if chloride ions were injected into the
neuron. If a series of anions of increasing~ hydrated
diameter ranging from potassium bromide to potassium acetate were injected into the neuron, the larger
anions did not affect the IPSP whilst the smaller
anions did. The threshold size was between 1.14 and
1.24 times the diameter of the hydrated potassium
ion. This value was identical to that found for the
IPSP in mammalian motoneurons.
13
that if the snail, crab or insect nerve-muscle preparation was perfused it was possible to obtain glutamate
in the peffusate following stimulation of the nerve.
We also tested various possible inhibitors such as
glutamate diethyl ester, glutamate methyl esters,
alpha aminopimelic acid and aIpha~aminoadipic acid,
but none of them were very powerful inhibitors of
glutamate. The lack of potent inhibitors has hindered
research on the role of excitatory amino acids in the
CNS (except for the N M D A system). Nevertheless, it
has generally become accepted that glutamate or
aspartate type compounds are probable transmitters
in the CNS.
ELECTROGENIC SODIUM PUMP
Roger Thomas showed if sodium ions were injected
into snail neurons there was a rapid hyperpolarization of the membrane potential by as much as 30 mV.
This hyperpolarization was inhibited if ouabain was
present or if the extracelhilar potassium concentration was reduced. The hyperpolarization was due to
the stimulation of an electrogenic sodium pump
which, due to the high resistance of the nerve membrane, produced a very rapid and big change in
membrane potential.
John Lambert showed that some snail neurons had
a high sodium permeability relative to the potassium
permeability and that these neurons had a greater
electrogenic sodium pump component of the membrane potential.
Barbara York showed that the snail neuron was
sensitive to the oxygen concentration around the
neuron and that reducing the Po2 brought about a
depolarization of the membrane potential, whilst
increasing the Po2 hyperpolarized the neuron, the
effect being prevented by ouabain or scillaren.
Sodium-injected neurons were more sensitive (A
22 mV) to changes in Po2 than were potassium injected neurons (A 8 mV). This indicated that the
electrogenic sodium pump component of the membrane potential was more sensitive to Po~ than was
the electro-diffusion (Nernst) component.
The electrogenic sodium pump had been considered for many years and thought to contribute only
one or two millivolts to the membrane potential. The
snail neuron provided the first example of a rapid and
major change in membrane potential due to the
activity of the sodium pump, and indicated a more
important role for metabolic pumps in nerve and
muscle activity. The role of the electrogenic sodium
pump in nerve and muscle tissues (especially mammalian cardiac muscle) is now more fully appreciated.
RECEPTOR IONOPHORE COMPLEXES
Once it was realized that a given receptor type
could be linked to different ionophores (ACh producing depolarizations in some neurons and hyperpolarization in other neurons) it was of interest to study
the relationship in more detail.
John Chad developed a ramped voltage clamp
system and showed that there were three different
types of neurons in Helix brain that responded to
ACh. (a) Those hyperpolarized by ACh, due to an
increase in chloride permeability, (b) Those depolarized by ACh, due to an increase in sodium permeability. (c) Those depolarized by ACh due to an increase
of both sodium and chloride permeability. The ACh
receptors linked to the sodium ionopbore were
blocked by hexametbonium whilst those linked to
the chloride ionophore were blocked by decamethonium.
Some snail nerve cells respond to two transmitters.
F1 is depolarized by ACh and by 5HT, both receptors
being linked to sodium ionophores (Fig. 4).
FA is hyperpolarized by ACh and by glutamate,
both receptors being linked to chloride ionophores.
Are the same sodium ionopbores linked to both
the ACh-R and 5HT-R and are the same chloride
ionophores linked to both the ACh-R and the
GIu-R?
John Chad showed that even when the neuron gave
its maximum current to application of ACh, it could
pass more current (have more ionophores open) when
5HT and ACh were added together. The increased
membrane conductance response to simultaneous
application of ACh and 5HT was equal to the
sum of the individual ACh and 5HT responses,
similarly for ACh and glutamate. It would seem that
each receptor (ACh-R, 5HT-R, GIu-R) is linked
to its own population of sodium or chloride
ionophores.
GLUTAMATEAS A NEUROTRANSMITrER
In the search for new neurotransmitters, the
general opinion in the 1960s was that the new transmitters would be complicated unfamiliar chemical
compounds. We showed in 1962 that a very familiar
chemical, L-glutamate, proved to be very good at
stimulating snail neurons and later showed that glutamate made insect and crustacean muscle contract, the
tissues often responding to nanomol concentrations,
Susan Piggot showed that snail neurons were 100
more times more sensitive to L-glutamate than to
D-glutamate. Lucy Leake and Avril Shapiro found
AXOPLASMIC TRANSPORT IN ISOLATED
BRAIN-NERVE TRUNK-MUSCLE
PREPARATIONS
The isolated snail brain can survive more than
24 hr in isolation and it is possible to set up brainnerve trunk-muscle preparations and study the
muscle contraction following brain stimulation.
This gave us the idea of putting the brain in an
isolated pool of saline containing radioactively
labelled material (glucose or glutamate) and having
the muscle in a second isolated pool of saline
14
G.A. KERKUT
Fig. 4. Electron micrograph of the neuropil in the snail brain, showing an expanded nerve axon (arrow)
probably containing two different neurotransmitters.
(non radioactive) with the two pools connected by the
nerve trunk. Care was taken using lanolin barriers to
see the radioactive material did not leak directly from
the brain pool to the muscle pool.
It was found that radioactivity went from the brain
to the muscle along the nerve trunk. It took about
20 min for the radioactivity to travel the 1 cm length
of nerve trunk. This rate of transport was much faster
than that suggested by Paul Weiss for amphibian
nerve. We developed an isolated frog spinal
cord-sciatic nerve-gastrocnemius preparations which
survived in isolation for more than 20 hr and found
that radioactive material could be transported along
the amphibian nerve trunk at fast rates.
It was also possible to put the radioactivity in
the muscle pool and find that after 24 hr there was
radioactivity in the snail brain or frog spinal
cord. This antidromic transport was slower (about
1 cm in 24 hr) than the orthodromic transport
(Fig. 5).
At a meeting in the USA in 1966 it appeared that
many American workers had found that slow rate of
axoplasmic transport described by Weiss and had
also some results giving fast rates of orthodromic
transport but had been cautious about revealing
the fast rates. However, they did not think that
antidromic transport occurred, or if it did so, it was
an artifact! Since then many laboratories have also
found antidromic transport of material from the
periphery to the nerve cell bodies and it is no longer
considered an artifact.
The use of isolated CNS-nerve trunk-muscle preparations that survive well for 12-24 hr has still not yet
been fully exploited and this point with be discussed
later on in this article.
INSECT CNS
Having obtained results from microelectrode
studies on intracellular potentials in snail neurons
following applications of drugs, it seemed interesting
to look at other isolated CNS preparations. The
cockroach CNS gave excellent extraceUular recordings but for some reason seemed difficult to study
with intracellular electrodes. Bob Pitman, using the
techniques we have developed for intracellular studies
on snail neurons, found several nerve cells in the
cockroach isolated ganglia that gave good resting
potentials, EP, IPSP and action potentials. Furthermore, the neurons responded well to application
of ACh which excited the cells and G A B A which
inhibited the neurons.
I heard that Edward Rowe, working at Ann Arbor,
Michigan, had obtained microelectrode records from
cockroach ganglia nerve cells but had difficulty in
getting his results accepted. I wrote to him saying that
we had similar results and were getting them ready
for publication, and asked if he would like to send
me a paper on his own work that could be published
before ours? He did so and we followed with
publication.
One summer, whilst our work was going on,
Graham Hoyle paid us a visit and Bob Pitman
showed him the work on the cockroach ganglia and
the recordings from the nerve cells. Graham had
thought that the recordings might not be from nerve
cells, but Alan Crossman had filled the ceils we
recorded from with Procion Yellow which enabled
the cells and axonal connections to be identified.
Graham Hoyle was convinced by these marked
neurons and their action potentials, and went back to
Isolated central nervous systems
A
lanolin
15
lanolin
RINGER
["1
nerve
cord
muscle ~
1
J
Frog Gastrocnemlus--sclatic--nerve cord
B
cut dotaaIr o o t l
cord
lanolin
FItOG
Fig. 5. Axoplasmic transport along the frog sciatic nerve trunk, between the isolated nerve cord and the
peripheral muscle. (A) The frog nerve cord is isolated, together with the sciatic nerve and the
gastrocnemius muscle. A double lanolin barrier is placed between the nerve cord and the muscle so that
radioactive material can be placed in either the nerve cord compartment, or the muscle compartment, and
no direct leakage of labelled material can take place. When the muscle is soaked in Ringer containing
labelled glutamate for 24 hr, radioactive material is found in the sciatic nerve trunk and also in the nerve
cord. (B) The effect of cutting the dorsal roots. Radioactive material still appears in the nerve cord, even
when the dorsal roots have been cut and the cut plugged with lanolin.
Eugene to work on these cells which he called dorsal
unpaired median cells (DUM). With his colleagues he
showed that they contained octopamine as a transmitter/modulator. I later got Graham to write a
chapter on these neurons for Comprehensive Insect
Physiology.
ISOLATEDINVERTEBRATECNSPREPARATIONS
The isolated snail brain provided excellent opportunities to study the membrane protentials of specific
nerve cells, their IPSP, EPSP, long term inhibition
and excitation, electrogenic sodium pumps, reaction
to anoxia, and their synaptic pharmacology. With
the techniques learnt from Helix neurons, and
the help of my colleagues listed in the bibliography at
the end of this article, it was possible to apply
these techniques to other isolated invertebrate CNS
preparations such as those of Hirudo medicinalis
(leech), Periplaneta americana (cockroach) Schisto-
C.B,P93/[A--B
.
cerca gregaria (locust), Limulus polyphemus (King
crab) and Tetrahymena, the ciliate protozoan that is
almost equivalent to a free-swimming neuron (Fig. 1).
We had intended to look at the CNS of Peripatus
but Ernst Florey and Graham Hoyle got there before
us!
The success with invertebrate CNS preparations
indicated that the vertebrate CNS might function
quite well in isolation and I decided to have a look
at the mammalian system to see what could be done
there. Neuroanatomists and histologists have been
studying the functional antomy of the mammalian
CNS for the last hundred years and we know more
about its structure and connections than for most
other central nervous systems. The wiring of the CNS
is of supreme importance and the anatomical background, together with modern computer analysis of
the electrical activity (information transfer, should
allow greater understanding of the functioning of the
CNS.
16
G.A. KERKUT
ISOLATED MAMMALIANCNS
PREPARATIONS
Henry Mcliwain and his colleagues had found
that stimulating rat brain slices doubled the rate of
respiration of the slice and that these brain slices
showed good electrical activity. It looked as if isolated pieces of the mammalian CNS might survive
quite well.
Together with Jeff Bagust, Kevin Green, Caroline
Herron, Ian Forsythe, Nagi Ibrahim and Melanie
Kelly, we set to work to see the extent to which we
could get large pieces of the mammalian CNS
functional. We were able to get good electrical activity from thin and thick slices of the rat cortex but I
was interested in larger functional systems and our
main effort has been in the isolated spinal cord,
extending to the brain stem, cerebellum and cerebrum.
It is possible to remove the whole spinal cord and
brain stem from 3-6-week-old hamsters, mice and
rats (animals that are fully mobile and active) and get
good electrical activity from these preparations. The
hamster has long spinal roots and so we tend to
use it especially to study reflex activity in the dorsal
and ventral roots. Furthermore, the preparation has
developed from the initial hemisected spinal cord to
our present preparations of the intact whole spinal
cord.
These preparations show the following activity:
(1) Spontaneous activity in the dorsal and ventral
roots.
(2) Stimulation of a dorsal root gives ipsilateral
monosynaptic and polysynaptic responses in the ventral root. These are reversibly blocked by saline
containing zero calcium and 2 mM Mn, i.e. involve
synaptic transmission,
(3) Stimulation of the dorsal root will give polysynaptic responses in the contralateral ventral
root.
(4) Preparations of the isolated spinal cord can
have identified peripheral nerve trunks going to antagonistic muscles and the activity in these motor
nerves studied following stimulation ofipsilateral and
contralateral sensory nerves.
(5) Stimulation of a dorsal root sends activity up
and down the spinal cord. The ascending action
potentials can reach the cuneate nucleus, synapse
there, and pass onwards to the brain stem.
(6) Stimulation of the brain stem sends activity
down the spinal cord and, depending on the site of
brain" stem, stimulation will augment or inhibit the
local spinal sensory-motor reflex.
(7) Stimulation of dorsal roots sends activity across
the spinal cord to the contralateral dorsal horns as
well as up and down the cord. There is a sensory
network in the spinal cord that could allow modulation of sensory inputs ipsilaterally and contralaterally. This suggests that the spinal cord has important
local area network connections in addition to the
through tracts going to and from the brain (Figs 6
and 7).
(8) The patterns of spontaneous activity in the
dorsal roots of the spinal cord .indicate that there are
segmental pattern generators in the spinal cord that
are functionally linked together.
(9) The segmental pattern generators that are in
adjacent segments of the spinal cord are more closely
correlated in their activity than those that are far
apart in the spinal cord. Complete transection of the
spinal cord removes the correlation between the
segmental pattern generators either side of the cut.
(10) The neurons in the spinal cord respond to
changes in the bathing saline. Changes in ionic
composition, the presence of drugs, blocking agents
and anaesthetics can all bring about a quick response.
There is no blood-brain barrier preventing access to
the neurons and synapses.
(11) Many of the neurons in the spinal cord
respond to drugs applied in the bathing saline. The
response is quick, the drug can be easily washed off
and the preparation recovers. This is the advantage
of not having a blood-brain barrier and should
allow more detailed study of the pharmacology of the
CNS.
(12) There are many interneurons functioning in
the isolated spinal cord and stimulation of adjacent
ventral or dorsal roots, or lateral pathways can
inhibit segmental reflex activity. The inhibition is
probably due to Renshaw cells and other glycine
systems.
There are thus many neurons and functional circuits active in these isolated mammalian CNS preparations and they remain functional in vitro for up to
24 hr after isolation. Conditions are not ideal because
the oxygenation of the deeper parts of the preparation is not sufficient and many nerve cells die from
anoxia, but it is possible to improve the oxygenation
of the system.
I
A
/3
+
+!II
......R4
Fig. 6. Diagram of the sensory connections in the mammalian spinal cord. There is a sensory network conducting
activity up, down and across the spinal cord. (A) Sensory
neurons in the dorsal ganglion. (B) Intemeurons in dorsal
spinal cord going from one side to the other, across the
dorsal mid-line. Stimulation of any of the dorsal roots, i.e.
L3 (left 3), leads to activity going up and down the
ipsilateral spinal cord, and it can be recorded in L4, L2 and
LI. Activity also crosses the spinal cord to dorsal root R3
(right 3) and goes up and down the contralateral spinal cord
to RI, R2, R3 and R4. Partial hemisection of the spinal cord
along the mid-line at levels L4 and L3 will still allow sensory
excitation caused by stimulating L4 to travel up the cord,
cross over to the other side and go up and down the
contralaterai side to produce activity in R1, R2 and also in
R3 and R4.
17
Isolated central nervous systems
D
g
)
<
..~....
.. -~.-..~.i
,. . . . . ,....
..:":~::.;-'."
• ".~...~
.'-'~'..~: :..
•: "%: ~ , ~ "
"~'::-.':':::
Fig. 7. Cajal's diagram of a transverse section of the mammalian spinal cord showing the commissures
connecting the dorsal horns of both sides of the cord (D and E). It is generally thought that sensory
information crosses to the ipsilateral and contralateral ventral horns of that segment (for local motor
reflexes) and also travels up the spinal cord to the brain. These dorsal commissures indicate that sensory
information is also transmitted to the contralateral dorsal (sensory) horn and provides the morphological
basis for the physiological local area sensory network shown in Fig. 6 (and also in the paper by Bagust
et al., later in this issue of the journal).
FUTURE
OF ISOLATED MAMMALIAN
PREPARATIONS
CNS
One of the problems in understanding how the CNS
works is that we tend to think in two-dimensional
models, in terms of diagrams on a page. But the CNS
works in three dimensions, probably with many
central processing units functioning in parallel, with
handshakes and cross-talk going on in all dimensions.
The isolated mammalian spinal cord preparation
offers many opportunities to study these systems. It
is possible dissect out tracts and pathways and determine the extent to which they interact. The pathways,
if functional, can be locally anaesthetized (reversibly
blocked) and the differences in firing patterns and
interactions studied.
Preliminary experiments show that higher pathways such as the pyramidal tract are also functional
in the isolated preparation. With improved technique
it will be possible to have simple dissected out circuits
with the spinal cord, brain stem, cerebellum, cerebral
cortex and basal ganglia all functioning.
The brain and spinal cord can then be considered
in terms of a computer with its plug-in boards of
circuitry. The dissected-out interconnected anatomical units of the isolated preparation will allow
recording from many sites in the CNS simultaneously, the boards (cerebellum, corpora
quadrigemina, auditory nerve input, optic nerve input, basal ganglia, cerebral cortex etc.) can be
plugged in or out (anaesthetised or recover) and so
provide an understanding of the parallel and hierarchical organization of the CNS (Fig. 8).
The complex shuttling back and forth of thousands
of electrical signals in the CNS each second is beyond
simple one- or two-channel analysis and requires new
techniques to enable us to understand what is going
on. With the development of sophisticated analytical
software for microcomputers that can take the electrical data simultaneously from many sites in the iso-
lated CNS, it will be easier for the research worker to
understand the more complex and subtle hierarchical,
parallel, differential, error-correcting, conditional
probability communications taking place within the
spinal cord and brain and so obtain a better appreciation of the multifarous systems at work, i.e. the
computers will enable us to understand what is going
on, and the isolated mammalian CNS preparations
will provide ideal data for such computer analysis.
It is always necessary to check the findings from in
vitro preparations with those in the intact living
animal. The two systems of analysis of CNS function
(in vitro and in vivo) go together, like two hands
grasping a problem and will allow greater progress in
the understanding of how the CNS works.
RETROSPECT
The study of the isolated central nervous system
has led to an increased understanding of the rules
determining the activity and interactions of nerve
cells.
Studies on the electrical activity of peripheral nerve
explained the membrane potential and action potential in terms of one potassium current and one
sodium current. Now we know of at least five potassium currents, three sodium currents, four calcium
currents and three chloride currents in CNS neurons.
Progress has gone from two chemical synaptic
transmitters to at least 30 and probably 100 if one
includes modulators. Once there was only one nenrotransmitter in the presynaptic terminal; now there
can be many in the one terminal; and of course the
number of different receptors for a given transmitter
has been subdivided so that any respectable transmitter will have at least three receptor subtypes.
It was assumed that a nerve cell at rest is isopotential throughout the whole of that cell. Now it is
probable that different parts of a cell can be at
18
G.A. KERKUT
/
/
S~SORY S ~
spinal cord-4thalamus
cortex
s p i n a l cx~l
cerebral cortex
~
EXTRA FYRAMIr~LMDIDRSYSTEM
~ I ~ R ~ I I ~
NYIDR SYS'I~
Fig. 8. Diagram of the mammalian CNS as a series of computer boards linked by connecting tracts. The
isolated mammalian CNS can be dissected to allow stimulation and recording at many sites in the CNS.
Only four systems are shown here as an example, but many more could be dissected out. The different
circuits could be considered as quasi two-dimensional printed circuit boards and the interactions between
the systems analysed. Local easily-reversed anaesthetics could be applied to connections to see the effect
of bringing a circuit in or out of the network. In this way the three-dimensional interactions in the
mammalian brain and spinal cord could be more easily investigated and understood.
different membrane potentials. Furthermore, the
ionic composition within a neuron is probably not
uniform and there is compartmentalization with
some regions (dendrites) having different ionic content and calcium sequestering properties from other
regions of the neuron.
Once all C N S neurons were equal; now you have
to know which neuron you are working on so as to
get repeatable experimental results. It is also important to appreciate the diurnal, monthly and yearly
cycles in neuronal activity in the CNS.
Much o f this new information has come from
studies on the isolated C N S and it is probable that
" y o u ain't seen nothing yet".
We have been fortunate in participating in some of
these discoveries, and this has made the scientific
work interesting and exciting. I have benefited greatly
from working with enthusiastic, gifted colleagues
who have helped make my progress more constructive than destructive, more helping than hindering
and more inquisitive than acquisitive.
Acknowledgements--I am most grateful to my colleagues
who participated in this meeting and to Jane Breese and
Lorraine Prout who took a major part in its organization.
I am also very grateful to Robert Walker for organizing the
meeting and for the past 30 years of valuable help and
collaboration, and to Robert Maxwell for his encouragement and support over the years and for his financial help
towards the cost of the meeting.
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(in chronological order)
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Kerkut G. A. and Taylor B. J. R. (1956) The sensitivity of
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T. M., Kerkut G. A. and Munday K. A. (1957) The
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Kerkut G. A. and Laverack M. S. (1957) The respiration of
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Haughton T. M., Kerkut G. A. and Munday K. A. (t958)
The oxygen dissociation and alkaline denaturation of
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temperature changes on the activity of poikilotherms.
Behaviour 13, 259-279.
Edwards M., Kerkut G. A., Munday K. A., Ingrain D. J.,
Saxena M. C. and Leach K. (1959) Electron spin
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Kerkut G. A., Edwards M. L., Leech K. and Munday K. A.
(1961) Free radicals in animal tissues. Sep. exp. 17, 497.
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Kerkut G. A. and Walker R. J. (1961) The resting potential
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Kerkut G. A. and Walker R. J. (1961) The effects of drugs
on the neurones of the snail. Comp. Biochem. Physiol. 3,
143-160.
Kerkut G. A. and Ridge R. M. A. P. (1961) The effect of
temperature changes on the resting potential of crab,
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Munday K. A. and Kerkut G. A. (1961) Free radicals in
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Kerkut G. A., Edwards M. L. and Munday K. A. (1962)
Free radicals in human hair. Life Sci. 4, 129-132.
Kerkut G. A. and Cottrell G. A. (1962) Neuropharmacology of the pharangeal retractor muscle of the snail
Helix aspersa. Life Sci. 6, 229-231.
Kerkut G. A and Cottrell G. A. (1962) Amino acids in the
blood and nervous system of Helix aspersa. Comp.
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Kerkut G. A. and Munday K. A. (1962). The effect of
copper on the tissue respiration of the crab Carcinus
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Kerkut G. A. and Ridge R. M. A. P. (1962) The effect of
temperature changes on the activity of the neurones of the
snail Helix aspersa. Comp. Biochem. Physiol. 5, 283-295.
Kerkut G. A. and Walker R. J. (1962). Is the action of
acetylcholine on the snail brain a physiological or a
pharmacological one? Arch. Int. Phys. Biochim. 70,
185-190.
Kerkut G. A. and Walker R. J. (1962) The specific chemical
sensitivity of Helix nerve cells. Comp. Biochem. Physiol.
7, 277-288.
Kerkut G. A. and Walker R. J. (1962) Marking individual
nerve cells through electrophoresis of ferrocyanide from
a microelectrode. Stain Tech. 37, 217-219.
Dain A., Kerkut G. A., Smith R. C., Munday K. A. and
Wilmshurst T. H. (1963) The interaction of fre¢ radicals
in proteins and melanin. Sep. Exp. 20, 76.
Kerkut G. A. and Cottrell G. A. (1963) Acetylcholine and
5-hydroxytryptamine in the snail brain. Comp. Biochem.
Physiol. 8, 53-63.
Kerkut G. A. and McLachlen K. R. (1963) A transistorised
nerve analogue. Med. Electrn. Biol. Engng 1, 101-103.
Kerkut G. A. and Thomas R. C. (1963). Anion permeability
of the inhibitory post-synaptic membrane of Helix neutones. Proc. Physiol. Soc., April 1963. J. Physiol., Lond.
168, 23-34.
Kerkut G. A. and Thomas R. C. (1963) Acetylcholine and
the spontaneous inhibitory post synaptic potentials in the
snail neurone. Comp. Biochem. Physiol. 8, 39--45.
Kerkut G. A. and Thomas R. C. (1964) The effect of anion
injection and changes in the external potassium and
chloride concentration on the reversal potentials of the
IPSP and acetylcholine. Comp. Biochem. Physiol. 11,
119-213.
Kerkut G. A., Thomas R. C. and Venning B. H. (1964) A
transistorized linear sweep circuit for determining reversal
potentials in nerve cells. Med. Electron. Biol. Engng 2,
425-430.
Kerkut G. A. (1965) Chemical transmission in the nervous
system of Helix aspersa. Symposium on Comparative
Neurophysiology, Tokyo, p. 32.
Kerkut G. A. (1965a) Liberation of glutamate at the snail
nerve muscle junction. Proc. 23rd Internat. Physiol. Congress, Tokyo, p. 912.
19
Kerkut G. A. (1965b) Chemical transmission in the nervous
system of Helix aspersa. Symposium on Comparative
Neurophysiology. Tokyo, Paper 12A, 4.
Kerkut G. A., Leake L. D., Shapira A., Cowan S. and
Walker R. J. 0965) The presence of glutamate in the
nerve muscle perfusates of Helix, Carcinus and Periplaneta. Comp. Biochem. Physiol. 15, 485--502.
Kerkut G. A., Shapira A. and Walker R. J. (1965). The
effect of acetylcholine, glutamate, and GABA on the
contractions of the perfused cockroach leg. Comp.
Biochem. Physiol. 16, 37-48.
Kerkut G. A. and Thomas R. C. (1965) An electrogenic
,sodium pump in snail nerve cells. Comp. Biochem.
Physiol. 14, 167-183.
Kerkut G. A. and Leake L. D. (1966) The effect of drugs
on the snail pharangeal retractor muscle. Comp. Biochem.
Physiol. 17, 623-633.
Kerkut G. A. and Meech R. W. (1966) The internal chloride
concentrations of H and D cells in the snail brain. Comp.
Biochem. Physiol. 19, 819-832.
Kerkut G. A., Sedden C. B. and Walker R. J. (1966)
The effect of dopa, r,-methyldopa and reserpine on the
dopamine content of the brain of the snail, Helix aspersa.
Comp. Biochem. Physiol. 18, 921-930.
Kerkut G. A. and Walker R. J. (1966) The effect of
L-glutamate, acetylcholine and gamma-aminobutyric acid
on the miniature end-plate potentials and contractors
of the coxal muscles of the cockroach, Periplaneta
americana. Comp. Biochem. Physiol. 17, 435~54.
Kerkut G. A., Woodhouse M. and Newman G. (1966)
Nerve muscle junction in the snail Helix aspersa. Comp.
Biochem. Physiol. 19, 309-311.
Boakes R. J., Kerkut G. A. and Munday K. A. (1967). The
effect of hypothermia on cortical evoked potentials. Life
Sci. 6, 457-459.
Chamerlain S. and Kerkut G. A. (1967). Voltage clamp
studies on snail (Helix aspersa) neurones. Nature. Lond.
216, 89.
Huggins A. K., Rick J. T. and Kerkut G. A. (1967) A
comparative sutdy of the intermediary metabolism of
L-glutamate in muscle and nervous tissue. Comp.
Biochem. Physiol. 21, 23-30.
Judge S. E., Kerkut G. A. and Walker R. J. (1967)
Interactions between two identified cells in the visceral
ganglion of the snail Helix pomatia. Experientia. 32,
596-597.
Kerkut G. A. (1967) Transport of glutamate to nerve
terminals. In Axoplasmic transport. Neurosci. Res. Prog.
Bull. 5, 322-325.
Kerkut G. A. (1967) Biochemical aspects of invertebrate
nerve cells. In Invertebrate Nervous Systems (Edited by
Wiersma C. A. G.), pp. 5-37. University Press, Chicago.
Kerkut G. A. and Gardner D. R. (1967) The role of calcium
ions in the action potentials of Helix aspersa neurones.
Comp. Biochem. Physiol. 20, 147-162.
Kerkut G. A., Sedden C. B. and Walker R. J. (1967) A
fluorescent microscopic and electrophysiological study of
the giant neurones of the ventral nerve cord of Hirudo
medicinalis. J. Physiol., Lond. 189, 83-85P.
Kerkut G. A., Shapira A. and Walker R. J. (1967) The
transport of labelled material from CNS Muscle along a
nerve trunk. Comp. Biochem. Physiol. 23, 727-748.
Kerkut G. A. and Walker R. J. (1967) The effect of
iontophoretic injection of L-glutamic acid and ),-amino-Bbutyric acid on the miniature end-plate potentials and
contractures of the coxal muscles of the cockroach
Periplaneta americana L. Comp. Biochem. Physiol. 20,
999-1003.
Kerkut G. A. and Walker R. J. (1967) The action of
acetylcholine, DOPAmine, and 5 hydroxytryptamine on
the spontaneous activity of the cells of Retzius of the leech
Hirudo medicinalis. Br. J. Pharmacol. Chemother. 30,
644-654.
20
G.A. KERKUT
Rick J. T. and Kerkut G. A. (1967) The comparative
production of GABA in bidirectionally bred behavioural
strains. Abstracts of First International Meeting of International Society for Neurochemistry, Strasbourg, 1967,
p. 177.
Rick J. T., Huggins A. K. and Kerkut G. A. (1967a) The
comparative production of y-amino butyric acid in the
Maudsley reactive and non-reactive strains of Rat. Comp.
Biochem. Physiol. 20, 1009-1012.
Gardner D. R. and Kerkut G. A. (1968) A comparison
of the effects of sodium and lithium ions on actions
potentials from Helix aspersa neurones. Comp. Biochem.
Physiol. 25, 33-48.
Kerkut G. A. (1968) Transport of material along nerves.
Ciba Foundation Symposium on Growth of the Nervous
System, 1968, pp. 220-229.
Kerkut G. A. (1968) The movements of chemicals in snail
neurones. Symposium on Neurobiology of Invertebrates,
Tihany (Edited by Salanki J.), pp. 341-352.
Kerkut G. A. and Horne N. (1968) Dopamine and longlasting inhibition of snail neurones. Life Sci. 7, 567-570.
Kerkut G. A., Pitman R. M. and Walker R. J. (1968)
Electrical activity in insect nerve cell bodies. Life Sci. 7,
605-608.
Kerkut G. A., Shapira A. and Walker R. J. (1968) Transport
of C-14 labelled material along nerve trunks. In Macromolecules and the Function of the Neuron. Excerpta
Medical Monographs (Edited by Lodin Z.), pp. 177-185.
Kerkut G. A., Walker R. J. and Woodruff G. W. (1968)
The effects of histamine and other naturally occurring
imidazoles on neurones of Helix aspersa. Br. J. Pharmacol. Chemother. 32, 241-252.
Newman G., Kerkut G. A. and Walker R. J. (1968) The
structure of the brain of Helix aspersa. Electron microscope localization of cholinesterase and amines. Syrup.
Zool. Soc. Lond. 22, 1-17.
Rick J. T., Morris D. and Kerkut G. A. (1968)
Cholinesterase, cholineacetyltransferase and the production of y-aminobutyric acid in the cerebral cortex of
five behavioral strains of rats. Life Sci. 7, 733-739.
Sedden C. B., Walker R. J. and Kerkut G. A. (1968) The
localization of dopamine and 5HT in neurones of Helix
aspersa. Proc. Syrup. Zoo. Soc. Lond. 22, 19-32.
Walker R. J., Woodruff G. N. and Kerkut G. A. (1968) The
effect of ACh and 5HT on the electrophysiological recordings from muscles fibres of the leech Hirudo medicinalis.
Comp. Biochem Physiol. 24, 987-990.
Walker R. J., Woodruff G. N., Glaizner B., Sedden C. B.
and Kerkut G. A. (1968) The pharmacology of Helix
dopamine receptor of specific neurones in the snail, Helix
aspersa. Comp. Biochem. Physiol. 24, 455-469.
Chamberlain S. G. and Kerkut G. A. (1969) Voltage clamp
analysis of the sodium and calcium inward currents in
snail neurones. Comp. Biochem. Physiol. 28, 787-803.
Curtis D. J. and Kerkut G. A. (1969) The effect of reserpine
on the vesicle content of Helix aspersa cerebral ganglia.
Comp. tliochem. Physiol. 30, 835-840.
Kerkut G. A. (1969) Regulation of the rhythmic activity of
the heart. Experientia Suppl. 15, 202. Symposium on
Comparative Physiology of the Heart, Dartmouth.
Kerkut G. A. (1969) Comparative Physiology of the heart;
summary and conclusions. Experientia Suppl. 15,
266-270. Symposium on Comparative Physiology of the
Heart, Dartmouth.
Kerkut G. A. (1969) A. Buffering capacity of snail blood.
B. To determine the choline esterase activity in snail
blood. Exp. Physiol. Biochem. 1, 111-124.
Kerkut G. A. (1969) The missing pieces. Inaugural lecture,
Southampton University.
Kerkut G. A. (1969) The use of snail neurons in neurophysiological studies. Endeavour XXVIH, (103), 22-26,
Kerkut G. A. (1969) Neurochemistry of invertebrates. In
The Handbook of Neurochemistry (Edited by Lajtha A.),
Vol. 2. Chpt. 23, pp. 539-562. Plenum Press. New
York.
Kerkut G. A., Brown L. C. and Walker R. J. (1969)
Cholinergic IPSP by stimulation of the electrogenic
sodium pump. Nature, Lond. 223, 864-865.
Kerkut G. A., Brown L. C. and Walker R. J. (1969) Post
synaptic stimulation of the electrogenic sodium pump.
Life Sci. 8, 297-300.
Kerkut G. A., Pitman R. M. and Walker R. J. (1969)
Sensitivity of neurones of the insect central nervous
system to iontophoretically applied acetylcholine or
GABA. Nature, Lond. 222, 1075-I076.
Kerkut G, A., Rick J. T. and Huggins A. K. (1969) The
intermediary metabolism in vitro of glucose and acetate
by ganglia from Helix aspersa, and the effects of
amphetamine. Comp. Biochem. Physiol. 28, 765-771.
Kerkut G. A. and York B. (1969) The oxygen sensitivity of
the electrogenic sodium pump in snail neurones. Comp.
Biochem. Physiol. 28, 1125-1134.
Kerkut G. A., Pitman R. M. and Walker R. W. (1969)
Iontophoretic application of acetylcholine and GABA
onto insect central neurones. Comp. Biochem. Physiol. 31,
611-633.
Kerkut G. A., Walker R. J. and Woodruff G. N. (1969) The
action of Acetylcholine on the neurones of the snail Helix
aspersa. Proc. 4th lnternat. Congr. Pharmacol, 5, 84-95.
Kerkut G. A. and Shapira A. (1968) A Thin-layer chromatography of amino acids and sugars. B. The snail
Nerve-muscle preparation. C. Perfusion of the cockroach
leg. Exp, Physiol. Biochem. 1, 353-370.
Marsden C. A. and Kerkut G. A. (1969) The cellular
localization of monamines in invertebrates using the
Edwards Pearse tissue freeze dryer. Exp. physiol. Biochem
2, 327-360.
Woodruff G. N., Oniwinde A. B. and Kerkut G. A. (1969)
Histamine in tissues of the snail crab, goldfish, frog and
mous. Comp. Biochem. Physiol. 31, 599-603.
Kerkut, G. A. Ralph, K., Walker R. J., Woodruff G. N. and
Woods R. (1970). Excitation in the molluscan central
nervous system. In Excitatory Synaptic Mechanisms
(Edited by Andersen P. and Jansen J.), pp. 105-117.
Universitetsforlaget, Oslo.
Kerkut G. A., French M. C. and Walker R. J. (1970) The
location of axonal pathways of identifiable neurones of
Helix aspersa using the dye Procion Yellow M-4R. Comp.
Biochem. Physiol. 32, 618-690.
Kerkut G. A., Newton L. C., Pitman R. M., Walker R. J.
and Woodruff G. N. (1970) Acetylcholine receptors of
invertebrate neurones. Br. J. Pharmacol. 40, 486--7P.
Kerkut G. A., Oliver G. W. O., Rick J. T. and Walker R. J.
(1970) Biochemical changes during learning in an Insect
ganglion. Nature, Lond. 227, 722-723.
Kerkut G. A., Oliver G. W. O., Rick J. T. and Walker R. J.
(1970) The effects of drugs on learning in a simple
preparation. Comp. gen. Pharmacol. 1, 437-484.
Kerkut G. A., Ralph K. L., Walker R, J. and Woodruff
G. N. (1970) The effect of drug pretreatment on synaptic
activity in Helix brain. Br, J. Pharmacol. 40, 561-3P.
Walker R. J., Lambert J. D. C., WoodruffG. N. and Kerkut
G. A. (1970) Action potential shape and frequency as
criteria for neuron identification in the snail, Helix
aspersa. Comp. gen Pharmacol. 1, 409-425.
Walker R. J., Ralph K. L., Woodruff G. N. and Kerkut
G. A. (1970) Effect of drugs on excitatory and inhibitory
potentials in Helix aspersa. Experientia 27, 281-282.
Walker R. J., WoodruffG. N. and Kerkut G. A. (1970) The
action of four prostaglandins, El, E2, F1 a and F2a on the
spontaneous activity and on the response to acetylcholine
of neurones from the snail Helix aspersa. Comp. Gen.
Pharmacol. 1, 69-72.
Walker R. J., Woodruff G. N. and Kerkut G. A. (1970) The
action of cholinergic antagonists on spontaneous excitatory potentials recorded from the body wall muscles of the
Isolated central nervous systems
leech, Hirudo medicinalis. Comp. Biochem. Physiol. 32,
691-701.
Woodruff G. N., Walker R. J. and Kerkut G. A. (1970)
Actions of ergomctrine on catecbolamine receptors in the
guinea-pig vas deferens and in the snail brain. Comp. gen.
Pharmacol. 1, 54-60.
Marsden C. and Kerkut G. A. (1970) Quantitative studies
on the neurons of the leech, Hirudo medicinalis. Comp.
gen. Pharmacol. 1, 293-298.
Pitman R. M. and Kerkut G. A. (1970) Comparison of the
actions of the iontophoretically applied ACh and GABA,
with the EPSP and IPSP cockroach central neurones.
Comp. gen. Pharmacol. 1, 221-230.
Beesley P., Emson P. C. and Kerkut G. A. (1971) Change
in Km of insect ChE after behavioural training.
J. Physiol., Lond. 221, 26-27.
Crossman A. R., Kerkut G. A. and Walker R. J. (1971)
Axon pathways of electrically excitable nerve cells bodies
in the insect central nervous systems. J. Physiol., Lond
218, 55--56P.
Emson P. C. and Kerkut G. A. (1971) Acetylcholinesterase
in snail brain. Comp. Biochem. Physiol. 39B, 879-889.
Emson P., Walker R. J. and Kerkut G. A. (1971) Chemical
changes in a molluscan ganglion associated with learning.
Comp. Biochem. Physiol. 40B, 223-239.
Kerkut G. A., Beesley P., Emson P., Oliver G. W. O. and
Walker R. J. (1971) Reduction in ChE during shock
avoidance learning in the cockroach CNS. Comp.
Biochem. Physiol. 3913, 423-424.
Oliver G. W. O., Taberner P. V., Rick J. T and Kerkut G. A.
(1971) Changes in GABA level, GAD and ChE activity
in CNS of an insect during learning. Comp. Biochem.
Physiol. 38B, 529-535.
Rick J. T., Tunnicliff G., Kerkut G. A., Fulker D. W.,
Wilcock J. and Broadhurst P. L. (1971) GABA production in brain cortex related to activity and avoidance
behavior in eight strains of rats. Brain Res. 32,
234-238.
Walker R. J., Crossman A. R., Woodruff G. N and Kerkut
G. A. (1971) The effect of bieuculline on the gamma
amino butyric acid (GABA) receptors of neurones of
Periplaneta americana and Helix aspersa. Brain Res. 33,
75-82.
Walker R. J., Ralph K. L., Woodruff G. N and Kerkut
G. A. (1971) Evidence for a dopamine inhibitory postsynaptic potential in the brain of Helix aspersa. Comp.
gen Pharmacol. 2, 15-26.
Walker R. J., Woodruff G. N. and Kerkut G. A. (1971) The
effect of ibotenic acid and muscimol on single neurons of
the snail, Helix aspersa. Comp. gen. Pharmacol. 2,
168-174.
Woodruff G. N., Walker R. J. and Kerkut G. A. (1971)
Antagonism by derivatives of lysergic acid of the effect of
dopamine on Helix neurones. Euro. J. Pharmacol., 14,
77-80.
Grossman A. R., Kerkut G. A. and Walker R. J. (1972)
Electrophysiological studies on the axon pathways of
specified nerve cells in the central ganglia of two insect
species, Periplaneta americana and Schistocerca gregaria.
Comp. Biochem. Physiol. 43A, 393--415.
Kerkut G. A., Emson P. C. and Bcesley P. W. (1972) Effect
of leg-raising learning on protein synthesis and ChE
activity in the cockroach CNS. Comp. Biochem Physiol
41B, 635~o45.
Kurkut G. A., Emson P. C., Brirnblecome R. W., Beesley
P., Oliver G. W. and Walker R. J. (1972) Changes in the
properties of acetylcholine esterase in the invertebrate
central nervous system. Progr. Brain Res. 36, 65-77.
Osborne R. H. and Kerkut G. A. (1972) Inhibition of
noradrenaline biosynthesis and its effects on learning in
rats. Comp. gen Pharmacol. 3, 359-362.
Taberner P. V., Barnett J. E. G. and Kerkut G. A. (1972)
Preparation of succinic semialdehyde: its colorimetric
21
estimation as an assay for GABA aminotransferase.
J. Neurochem. 19, 95-99.
Taberner P. V., Rick J. T. and Kerkut G. A. (1972) The
action of gamma hydroxybutyric acid on cerebral glucose
metabolism. J. Neurochem. 19, 245-254.
Taberner P. V., Rick J. T. and Kerkut G. A. (1972)
Metabolic factors involved in the interaction between
pyrazole and butane-1, 4-diol and 4-hydroxybutyric acid.
Life Sci. 11, 335-341.
Akhtar M., Azanza M. J., Kerkut G. A., Piggott S. M.,
Rasool C. G., Walker R. J. and Woodruff G. N. (1973)
Studies on amino acid receptors from neurones of Helix
aspersa. J. Physiol., Lond., 232, 62P.
Durkin T. P. and Kerkut G. A. (1973) Rat brain acetylcholinesterase; automated regional activity measurements
after various behavioural treatments. Biochem. Soc.
Trans. 1, 1310-1313.
Gayton R. J., Kerkut G. A., Lambert J. D. C., Loker J. E.
and Walker R. J. (1973). Mapping of nerve cells in the
brain of the snail Helix aspersa. J. Physiol., Lond. 232,
65P.
Kerkut G. A. (1973) Cateeliolamines in invertebrates Brit.
Med. Bull. 29, 100-104.
Rick J. T., Taberner P. V. and Kerkut G. A. (1973) Gamma
hydroxybutryic acid, imidazoleacetic acid, cerebral
metabolism and induced sleep. Israel J. reed. Sci. 9
(suppl.), 55--62.
Emerson L. and Kerkut G. A. (1974) Effect of oral administration of degraded carrageenan on the induction of
gastric ulcers in rats treated with giueocorticoids. J. comp.
Pathol. 84, 151-159.
Kerkut G. A. and Durkin T. M. P. (1974) The effect of
nembutal and electrical stimulation on the AChE activity
in 12 sites in the rat brain. In Neurobiological Basis of
Memory Formation (Edited by Matthies H.), pp. 229-235.
Veb Verlag Volk und Gesundheit, Berlin.
Kerkut G. A., Nicolaidis S., Piggott S. M., Rasool C. G. and
Walker R. J. (1974) The effect of analogues of giutamic
acid on the glutamate receptors of Helix neurones. Br. J.
Pharmacol. 51, 134--i35.
Kerkut G. A. and Wheal H. V. (1974) The effect of diethyl
ester L-glutamate on evoked excitatory junction potentials
at the crustacean neuromuscular junction. Brain Res. 82,
338-340.
Lambert J. D. C., Kerkut G. A. and Walker R. J. (1974)
The electrogenic sodium pump and membrane potential
of identified neurones in Helix aspersa. Comp. Biochem.
PhysioL 47A, 892-916.
Kerkut G. A. (1975) Axoplasmic Transport. Comp.
Biochem. Physiol. 51A, 701-704.
Kerkut G. A., Lambert J. D. C., Gayton R. J., Loker J. E.
and Walker R. J. (1975) Mapping of nerve cells in the
suboesophageal ganglia of Helix aspersa. Comp. Biochem.
Physiol. 50A, 1-25.
Kerkut G. A., Loker J. E. and Walker R. J. (1975)
An electrophysiological, pharmacological and fluorescent
study on six identified neurones from the brain of Planorbis corneus. Comp. Biochem. Physiol. 51C, 83-89.
Kerkut G. A., Piggott S. M. and Walker R. J. (1975)
Structure-activity studies on glutamate receptor sites of
three identifiable neurones in the sub-oesophageal ganglia
of Helix ~persa. Structure-activity studies on Helix
glutamate receptors. Comp. Biochem. Physiol. 51C,
91-100.
Kerkut G. A., Piggott S. M. and Walker R. J. (1975) The
antagonist effect of alpha-amino-pimelic acid on glutamate-induced inhibitions of Helix neurones. Brain Res.
86, 139-143.
Kerkut G. A. and Wheal H. V. (1975) The Excitatory Action
of Kainic Acid (KA) on the Crustacean Neuromuscular
Junction. Canadian Institute of Physiology. 68pp.
Kerkut G. A. and Wheal H. V. (1975) The antagonistic
action of L-glutamate diethyl ester on the excitatory
22
G.A. KERKUT
post-synaptic membrane of the crab neuromuscular junction. Comp. Biochem. Physiol. 51C, 79-81.
Kerkut G. A. and Walker R. J. (1975) Nervous system, eye
and statocyst. Pulmonates, Vol. 1., Functional Anatomy
and Physiology. (Edited by Fretter V. and Peake J.),
pp. 165-244. Academic Press, London.
Loker J. E., Kerkut G. A. and Walker R. J. (1975) An
electrophysiological, pharmacological and fluorescent
study on twelve identified neurones from the brain of
Helix aspersa. Comp. Biochem. Physiol. 50A, 443-452.
Anand R., Gore M. G. and Kerkut G. A. (1976) Acetylcholinesterase changes in the thalamus of rat brain
after anaesthesia and electrical stimulation. Biochemical
society Transactions, 563rd Meeting, London.
Anand R., Gore M. G. and Kerkut G. A. (1976) The effect
of spermine and spermidine on the hydrolysis of acetylthiocholine in the presence of rat caudate nucleus
homogenate of acetylcholinesterase from Electrophorus
electricus. J, Neurochem. 27, 381-385.
Anand R., Gore M. G. and Kerkut G. A. (1976) An
automated method for acetylcholinesterase kinetics.
Analyt. Biochem. 70, 463-469.
Evans C. and Kerkut G. A. (1976) Changes in the activities
of acetylcholinesterase and pseudocholinesterase in
regions of the rat brain after behavioural treatment.
Biochemical Society Transactions, 563rd Meeting,
London.
Judge S. E., Kerkut G. A. and Walker R. J. (1976) Common
connections among identified cells in the central ganglia
of the snail, Helix. Comp. Biochem. Physiol. 155A,
247-251.
Kerkut G. A. (1976) A commentary on Comparative
Pharmacology. Comp. Biochem. Physiol. 55, 1-3.
Kerkut G. A. (1976) Retrospect and Prospect. Neurobiology
of lnvertebrates, Gastropoda Brain, pp. 645--649. Tihany,
1975.
Wheal H. V. and Kerkut G. A. (1976) Structure activity
studies on the excitatory receptor of the crustacean
neuromuscular junction. Comp. Biochem. Physiol. 5317,
51-55.
Kerkut G. A. and Wheal H. V. (1976) Electrophysiological
and morphological investigations on the neuromuscular
junction of the hermit crab, Eupagurus Bernhardus. Comp.
Biochem. Physiol. 54A, 13-18.
Wheal H. V. and Kerkut G. A. (1976) The pre- and
post-synaptic actions of 5HT in crustacea. Comp.
Biochem. Physiol. 54C, 67-70.
Chad J. A., Kerkut G. and Walker R. J. (1977) Triangular
ramp clamping of Helix neurones during acetylcholine
application. J. Physiol., Lond, 203, 44P.
Evans C. A. and Kerkut G. A. (1977) The effects of
pentobarbitone-sodium anaesthesia, shock avoidance
conditioning and electrical shock on acetylcholinesterase
activity and protein content in regions of the rat brain.
J. Neurochem. 28, 829-834.
Haynes L. W. and Kerkut G. A. (1977) Facilitation of
Inhibitory Post-synaptic potentials in central neurones of
Helix aspersa. Comp. Biochem. Physiol. 59A, 311-323.
Haynes L. W., Kerkut G. A. (1977) Response time constants
in snail neurones. Experientia 33, 1482-1483.
Judge S. E., Kerkut G. A. and Walker R. J. (1977)
Properties of an identified synaptic pathway in the visceral ganglion of Helix aspersa. Comp. Biochem. Physiol.
57C, 101-106.
Piggott S. M., Kerkut G. A. and Walker R. J. (1977)
The actions of picrotoxin, strychnine, bicuculline and
other convulsants and antagonists on the responses to
acetylcholine giutamic acid and gamma-aminobutyric
acid on Helix neurones. Comp. Biochem. Physiol. 57C,
107-116.
Walker R. J. and Kerkut G. A. (1977) The actions of
nicotinic and muscarinic cholinomimetics and a series
of choline esters on two identified neurones in the
brain of Helix aspersa. Comp. Biochem. Physiol. 56C,
179-187.
Haynes L. W. and Kerkut G. A. (1978) Relationship of AP
frequency adaptation to the size of afterhyperpolarization
and to membrane conductivity in neurones of Helix
aspersa. Comp. Biochem. Physiol. 60A, 91-97.
Haynes L. W. and Kerkut G. A. (1978) Passive and active
electrical properties of two giant neurones in Helix
aspersa. Comp. Biochem. PhysioL 60A, 133-138.
Judge S. E., Kerkut G. A. and Walker R. J. (1978)
Long-lasting hyperpolarization in a pacemaker neurone
Comp. Biochem. PhysioL 61A, 475-481.
Kerkut G. A. (1978) The snail brain in pharmacological
screening and research. Gen. Pharmacol. 9, 79-80.
Sharp G. A., Fitzsimons J. T. R. and Kerkut G. A. (1978)
Microtubular ATPase in Carcinus and Helix Nerve.
Comp. Biochem. Physiol. 61A, 297-301.
Walker R. J. and Kerkut G. A. (1978) The first family
(adrenaline, noradrenaline, dopamine, octopamine, tyramine, phenylethanolamine and phenylethylamine). Comp.
Biochem. Physiol. 61C, 261-266.
Bagust J., Fitzsimons J. T. R. and Kerkut G. A. (1979)
Evidence for intergrating activity in the isolated intestinal
nerve of Helix aspersa. Comp. Biochem. Physiol. 62A,
397-408.
Bagust J. and Kerkut G. A. (1979) Some effects of magnesium ions upon conduction and synaptic activity in
the isolated spinal cord of the mouse. Brain Res 177,
410-413.
Chad J. E., Kerkut G. A. and Walker R. J. (1979) Ramped
voltage clamp study of the action of acetylcholine on
three types of neurons in the snail (Helix aspersa) brain.
Comp. Biochem. Physiol. 63C, 269-278.
Kai-Kai M. A. and Kerkut G. A. (1979) Mapping and
ultrastructure of neuroscrecretory cells in the brain of
Helix aspersa. Comp. Biochem. PhysioL 64A, 97-107.
Sharp G., Fitzsimons J. T. R. and Kerkut G. A. (1979) EM
localization of ATPase on microtubules in Tetrahymena
vorax. Comp. Biochem. Physiol. 63A, 253-260.
Yavari P., Walker R. J. and Kerkut G. A. (1979) The effect
of D-tubocurarine on the responses of snail neurons
to Ach. 5-HT, glutamate and dopamine---receptors or
ionophores? Comp. Biochem. Physiol. 64C, 101-I 14.
Yavari P., Walker R. J. and Kerkut G. A. (1979) The pA2
values of cholinergic antagonists on identified neurons of
the snail Helix aspersa. Comp. Biochem. Physiol. 63C,
39-52.
Adeoshun I. O., Kerkut G. A. and Wheal H. V. (1980)
Orthodromic activation of the ventrolateral thalamus in
the rat by stimulation ofipsilateral somatosensory cortex.
J. PhysioL, Lond. 307, 54-55P.
Bagust J. and Kerkut G. A. (1980) The use of the transition
elements manganese, cobalt and nickel as synaptic blocking agents on isolated, hemisected, mouse spinal cord.
Brain Res. 182, 474-477.
Chad J. E. and Kerkut G. A. (1980) Acetylcholine induced
membrane current fluctuations differ according to the
ionic species involved. J. Physiol. 303, 82-83P.
Kerkut G. A. (1980) Can fibre optic systems drive lower
motoneurones? Progr. Neurobiol. 14, 1-23.
Kerkut G. A., Sharp G. A and Fitzsimons J. T. R. (1980)
ATPase associated with microtubules in Tetrahymena,
Helix, Carcinusand Rattus. Comp. Biochem. Physiol. 6711,
485-492.
Sharp G. A., Fitzsimons J. T. RI and Kerkut G. A. (1980)
Electron microscopic localization of an ATPas¢ associated with microtubules in the cerebral cortex of the rat.
Comp. Biochem. Physiol. 66A, 415-429.
Walker R. J., James V. A., Roberts C. J. and Kerkut
G. A. (1980) Neurotransmitter receptors in invertebrates.
Receptors for Neurotransmitters, Hormones and Pheromones in lnsects (Edited by Satelle D. B.), pp. 41-57.
Elsevier/North-Holland Biomedical Press, Amsterdam.
Isolated central nervous systems
Bagust J., Green K. A. and Kerkut G. A. (1981) Strychnine
sensitive inhibition in the dorsal horn of mammalian
spinal cord. Br/an Re~. 217, 425-429.
Bagust J. and Kerkut G. A. (1981) An in vitro preparation
of the spinal cord of the mouse. In Electrophysiology of
Isolated Mammalian CNS Preparations(Edited by Kerkut
G. A. and Wheal H.), pp 337-365. Academic Press,
London.
Bagust J., Forsythe I. D. and Kerkut G. A. (1981) An
hemisected, /n vitro preparation of hamster spinal cord.
J. Physiol. 317, 11P.
Bagust J. and Kerkut G. A. (1981) Observations on the use
anaesthetics in the preparation of in vitro CNS material.
Neuropharmacology 30, 73-78.
Brown I. D., Connolly J. G. and Kerkut G. A. (1981)
Galvanotaxic response of Tetrahymena vorax. Comp.
Biochem. Physiol. 69C, 281-291.
Brown I. D. and Kerkut G. A. (1981) A study of the
chemokinetic effects of various pharmacological agents
upon Tetrahymena vorax. Comp. Biochem. Physiol. 69C,
275-280.
Chad J. E. and Kerkut G. A. (1981) Summation of membrane current conductance responses as evidence for
independent ionophore populations. Comp. Biochem.
Physiol. 69C, 61-65.
Chad J. E. and Kerkut G. A. (1981) The acetyicholine
induced membrane current fluctuations are characteristic
of the receptor-ionophore population involved. Comp.
Biochem. Physiol. 68C, 35-42.
Connolly J. G. and Kerkut G. A. (1981) The membrane
potentials of Tetrahymena vorax. Comp. Biochem.
Physiol. 69C, 265-273.
Fathi M. M. and Kerkut G. A. (1981). DFP or eserine shift
the dose-response curves of snail neuron El2 to ACh to
the left. Comp. Biochem. Physiol. 69C, 395-397.
Kerkut G. A. (1981) Introduction: The development of
isolated CNS preparations. In Electrophysiology of Isolated Mammalian CNS Preparations (Edited by Kerkut
G. A. and Wheal H. V.), pp. 1-14. Academic Press, New
York.
Kerkut G. A. King D. J. and Wheal H. V. (1981) Multimodal latency distribution of relay cells in the rat lateral
geniculate nucleus. J. Physiol., Lond. 317, 28-2P.
Walker R. J., James V. A., Roberts C. J. and Kerkut G. A.
(1981) Studies on amino acid receptors of Hirudo, Helix,
Limulus and Periplaneta. Adv. Physiol. Sci. 22, 161-190.
Bagust J., Forsythe I. D., Kerkut G. A. and Loots J. M.
(1982) Synaptic and non-synaptic components of the
dorsal horn potential in isolated hamster spinal cord
Brain Res. 233, 186-194.
Kerkut G. A. (1982) The development of isolated central
nervous system preparations. Comp. Biochem. Physiol.
72C, 161-169.
Azanza M. J. and Kerkut G. A. (1983) Actividad bioelectrica en encefalo aislado de lacerta atlantica. VI Reunion
Bienal Real Sociedad Espanola de Historia Natural,
Santiago, 13-17 September 1983.
Azanza M. J., Garin P. Sanz Esponera J. and Kerkut G. A.
(1983) Demostracion de la inervacion del diafragma
mediante tecnias de difusion axonica de cobalto, histoquimia e inmunocitoquimica. III Congreso Nacional de
Histologia, 15-18 September 1983, Departamento Interfacultativo de Citologia e Histologia, Universidad de
Murcia, Spain.
Kerkut G. A. (1983) Choosing a title for a paper. Comp.
Biochem. Physiol. 74A, 1.
King D. J., Wheal H. V., Sharma R. P. and Kerkut G. A.
(1983) Kainic acid derivatives as excitants of lateral
geniculate relay neurons. Brain Res. 262, 172-176.
Mat Jais A. M., Kerkut G. A. and Walker R. J. (1983) The
ionic mechanism associated with the biphasic glutamate
response on leech Retzius cells. Comp. Biochem. Physiol.
74(2, 425-432.
23
Connolly J. G. and Kerkut G. A. (1983) Ion regulation and
membrane potential in Tetrahymena and Paramecium.
Comp. Bioehem. Physiol. 76A, 1-16.
Bagust J., Herron C. and Kerkut G. A. (1984) Spread
of activity in thick cortical slices. Brain Res. 293, 168-172.
Connolly J. G. and Kerkut G. A. (1984) An electrogenic
component in the membrane potential of Tetrahymena.
Comp. Biochem. Physiol. "rTA, 335-344.
Kerkut G. A. (1984) Acetylcholinesterase (EC3117). Gen.
Pharmacol. 15, 375-378.
Mat Jais A. M., Sharma R. P., Kerkut G. A. and Walker
R. J. (1984) The halomethylketone derivative L-GIu-DL
ALaCH2Cl and NMDA as selective antagonists against
L-glutamate and kainaite excitatioin on the Retzius cells
of the leech Hirudo medicinalis. Comp. Biochem. Physiol.
77C, 385-398.
Mortlock A. M., Fitzsimmons J. T. R. and Kerkut G. A.
(1984) The effects of farnesol on the later stage nauplius
and free swimming cypris larvae of Eliminius modestus.
Comp. Biochem. Physiol. 78A, 345-357.
Connolly J. G., Brown I. D., Lee A. G. and Kerkut G. A.
(1985) Changes in lipid fluidity and fatty acid composition
with altered culture temperature in Tetrahymena pyriformis NTI. Comp. Biochem. Physiol. 81A, 287-292.
Connolly J. G., Brown I. A., Lee A. G. and Kerkut G. A.
(1985) The effects of temperature upon the electrophysiological properties of Tetrahymena pyriformis NTI. Comp.
Biochem. Physiol. 81A, 293-302.
Connolly J. G., Brown I. A., Lee A .G. and Kerkut G. A.
(1985) Temperature dependent changes in the swimming
behaviour of Tetrahymenis pyriformis NT1 and their
interrelationship with the electrophysiology and the state
of the membrane lipids. Comp. Biochem. Physiol. 81A,
303-310.
Bagust J., Kelly M. E. M. and Kerkut G. A. (1985) An
isolated mammalian brain stem-spinal cord preparation
suitable for the investigation of descending control of
motor activity. Brain Res. 327, 370-374.
Bagust J., Jordan P. M., Kelly M. E. M. and Kerkut G. A.
(1985) Effect of delta aminolaevulinic acid on activity
in the isolated, hemisected mammalian spinal cord.
Neurosci. Lett. (Suppl. 21), $84.
Bagust J., Forsythe I. D. and Kerkut G. A. (1985) An
investigation of the dorsal root reflex using an in vitro
preparation of the hamster spinal cord. Brain Res. 331,
31 5-325.
Bagust J., Ibrahim N. I. and Kerkut G. A. (1985) Effects of
bath-applied GABA on the firing pattern of cells in an in
vitro preparation of mammalian cerebral cortex. Neuropharmacology 24, 551-554.
Bagt:st J., Forsythe I. D. and Kerkut G. A. (1985) Demonstration of the synaptic origin of primary afferentdepolarization in the isolated spinal cord of the hamster.
Brain Res. 341, 385-389.
Hassoni A. A., Kerkut G. A. and Walker R. J. (1985) The
action of cholinomimetic and cholinolytic agents, hemicholinium 3 and alpha and beta bungarotoxin on the
body wall muscles of the earthworm Lumbricus terrestris.
Comp. Biochem. Physiol. 82C, 179-192.
Kerkut G. A. (1985) Microcomputers; the revolution of our
time. In Microcomputers in the Neurosciences (Edited by
Kerkut G. A.), pp. 1-8. Oxford University Press, Oxford.
Orson N. V., Fitzsimmons J. T. R. and Kerkut G. A. (1985)
Structural effects of external media on isolated myelinated
axons. Comp. Biochem. Physiol. 80A, 247-256.
Bagust J. and Kerkut G. A. (1987) Crossed reflex activity in
an entire, isolated, spinal cord preparation taken from
juvenile rodents. Brain Res. 411, 397-399.
Bagust J., Kerkut G. A., Rakkah N. I. A. and Tyler A. W.
(1987) Correlation in the patterns of spontaneous firing
from lumber dorsal roots on opposite sides of the cord
recorded from isolated spinal cords of mice and hamsters.
J. Physiol., Lond. 394, 156P.
24
G. A. KERKUT
AI-Zamil Z. M., Bagust J. and Kerkut G. A. (1988) The
effect of aminopyridines on the activity recorded in the
dorsal roots of an isolated hamster spinal cord preparation. Gen. Pharmacol. 19, 189-193.
Bagust J., Kerkut G. A., Rakkah N. I. A. and Tyler A. W.
(1988) An isolated whole-cord preparation of golden
hamster spinal cord which allows investigation of crossed
reflex activity. J. Physiol., Lond. 400, 4P.
Bagust J. and Kerkut G. A. (1988) Evidence for widespread
linkage of spinal dorsal root activity in an isolated
hamster spinal cord preparation. J. Physiol., Lond. 400,
59P.
Kerkut G. A. (1988) The origins of "Comparative Biochemistry and Physiology". Comp. Biochem. Physiol.
90A, 1-3.
Kerkut G. A. (1988) Possible evolutionary futures for
mankind. Comp. Biochem. Physiol. 90A, 5-10.
Books
The Invertebrata, By Borradaile L. A., Potts F. A., Eastham
L. E. S. and Saunders J. T. Cambridge University Press,
Cambridge, 3rd edition (1958) and 4th edition (1961)
revised by Kerkut G. A.
Implications of Evolution, By G. A. Kerkut (1961).
Pergamon Press, Oxford.
Experiments in Physiology and Biochemistry, Edited by
G. A. Kerkut. 6 volumes (1968-1973). Academic Press,
London.
The Electrogenic Sodium Pump, By G. A. Kerkut and
B. York (1971). Scientechnica, Bristol.
Electrophysiology of Isolated Mammalian CNS Preparations,
Edited by G. A. Kerkut and H. V. Wheal (1981).
Academic Press, London.
Microcomputers in the Neurosciences, Edited by G. A.
Kerkut (1985). Clarendon Press, Oxford.
Comprehensive Insect Physiology, Biochemistry and Pharmacology, Edited by G. A. Kerkut and L. I. Gilbert.
12 volumes (1985). Pergamon Press, Oxford.
Journals
Comparative Biochemistry and Physiology, Edited by
G. A. Kerkut (from 1960). Pergamon Press, Oxford.
Progress in Neurobiology, Edited by G. A. Kerkut and
J. V. Phillis (from 1973). Pergamon Press, Oxford.
International Series of Monographs in Pure and Applied
Biology, Zoology Division, Pergamon Press, Oxford (General
Editor: G. A. Kerkut)
Vol. 1. Raven--An Outline of Developmental
Physiology.
Vol. 2. Raven--Morphogenesis: The Analysis of
Molluscan Development.
Vol. 3. Savory--Instinctive Living.
Vol. 4. Kerkut--Implications of Evolution.
Vol. 5. Tartar--Tbe Biology of Stentor.
Vol. 6. Jenkin--Animal Hormones, A Comparative
Survey; Kinetic and Metabolic Hormones.
Vol. 7. Corliss--The Ciliated Protozoa.
Vol. 8. George---The Brain as a Computer.
Vol. 9. Arthur--Ticks and Disease.
Vol. I0. Ravcn--Oogenesis.
Vol. !I. Mann--Leeches (Hirudinea).
Vol. 12. Sleigh--The Biology of Cilia and Flagella.
Vol. 13. Pitelka--Electronmicroscopic Structure of
Protozoa.
Vol. 14. Fingerman--Tbe Control of Chromatophores.
Vol. 15. Laverack--The Physiology of Earthworms.
Vol. 16. Hadzi--The Evolution of the Metazoa.
Vol. 17. Clcments--The Physiology of Mosquitoes.
Vol. 18. Raymont--Plankton and Productivity in the
Oceans.
Vol. 19. Potts and Parry--Osmotic and Ionic Regulation
in Animals.
Vol. 20. Glasgow--The Distribution and Abundance of
Tsetse.
Vol. 21. Pantelouris--The Common Liver Fluke.
Vol. 22. Vandel--Biospeleology--The Biology of
Cavernicolous.
Vol. 23. Munday--Studies in Comparative Biochemisty.
Vol. 24. Robinson---Genetics of the Norway Rat.
Vol. 25. Needham--The Uniqueness of Biological
Materials.
Vol. 26. Bacci--Sex Determination.
Vol. 27. Jorgensen--Biology of Suspension Feeding.
Vol. 28. Gabe---Neurosecretion.
Vol. 29. Apter--Cybernetics and Development.
VoL 30. Sharov--Basic Arthropodan Stock.
Vol. 31. Bennett--The Aetiology of Compressed Air
Intoxication and Inert Gas Narcosis.
Vol. 32. Pantelouris--Introduetion to Animal Physiology
and Physiological Genetics.
Vot. 33. Hahn and Koldovsky--Utilization of Nutrients
during Postnatal Development.
Vol. 34. Troshin--The Cell and Environmental
Temperature.
Vol. 35. Duncan--The Molecular Properties and
Evolution of Excitable Cells.
Vol. 36. Johnson and Roots--Nerve Membranes. A
Study of the Biological and Chemical Aspects of
Neuron-Glia Relationships.
Vol. 37. Threadgold--The Ultrastructure of the Animal
Cell.
Vol. 38. Griffiths--Echidnas.
Vol. 39. Rybak--Prineiples of Zoophysioiogy.
Vol. 40. Purchon--The Biology of the Mollusca.
Vol. 41. Maupin--Blood Platelets in Man and Animals,
Vols. 1-2.
Vol. 42. Brondsted--Planarian Regeneration.
Vol. 43. Phillis--The Pharmacology of Synapses.
Vol. 44. Engelmann--The Physiology of Insect
Reproduction.
Vol. 45. Robinson---Genetics for Cat Breeders.
Vol. 46. Robinson--Lepidoptera Genetics.
Vol. 47. Jenkin---Control of Growth and Metamorphosis.
Vol. 48. Culley--The Pilchard: Biology and Exploitation.
Vol. 49. Binyon--Physiology of Echinoderms.
Vol. 50. Anderson--Embryology and Phylogeny in
Annelids and Arthropods.
Vol. 51. Boyden--Perspectives in Zoology.
Vol. 52. Cushing--The Detection of Fish.
Vol. 53. Huddart--The Comparative Structure and
Function of Muscle.
Vol. 54. Saunders--Insect Clocks.
Vol. 55. Matsuda--Morphology and Evolution of the
Insect Abdomen.