Sleep-wakefulness,
EEG and behavioral studies of chronic cats
without neocortex and striatum: the
"diencephalic" cat
Villablanca J, Marcus R
Departments of Psychiatry
and Anatomy University of California, Los
Angeles, USA
Introduction
The present research was initiated with the
intention of studying the electrothalamogram
(EThG) in relation to overt behavior in chronic
"diencephalic" cats, i. e., cats without
neocortex and striatum. In what appears to be
the only previous study in unrestrained, totally
neodecorticate cats chronically implanted with
subcortical electrodes, the EThG exhibited a
constant low voltage (20 µV) fast activity
irregardless of the behavioral state This EThG
pattern was recorded the day following the
operation and remained unchanged for several
months. However, there are reports of 8-12 c/sec
waxing and waning spindle bursts in the thalamus
of acute, immobilized, neodecorticate and
"diencephalic" cats; this activity has
essentially the same features of cortical
spindle activity of intact cats during
drowsiness and non-rapid eye movement sleep
(NREMs). The pioneer experiments of Morison and
Bassett are particularly interesting because the
spindle bursts which they observed in the
thalamus of neodecorticate cats anesthetized
with pentobarbital were present for up to three
postoperative days but disappeared
thereafter.
Due to the above discrepancies, and since
the objection has been raised that the EThG
synchrony in the acute experiments may be due to
irritation or diaschisis it was felt that a
reexamination of the EThG and behavior of
unrestrained freely moving decorticate cats was
justified. A clarification of this problem could
shed light upon the role of the thalamus in the
generation of rhythmic activity in the alpha
range of the-human EEG as well as upon its
behavioral significance.
Early in the course of this EThG study,
marked changes were noticed in the
sleep-wakefulness patterns, especially in rapid
eye movement sleep (REMs). These observations
led to a systematic study of the
sleep-wakefulness cycle in these " diencephalic"
animals, which became an important part of this
investigation. Recent research has emphasized
the role of caudal brain stem mechanisms
controffing REMs. However, the finding of motor
hyperactivity in neodecorticate and
"diencephalic" cats and dogs could imply that
forebrain lesions alter the sleep-wakefulness
cycle. Furthermore a virtual absence of NREMs in
decorticate cats and a clear, although
transitory suppression of REMs after lesions of
the basal forebrain area in cats has been
recently demonstrated. Because of these last
mentioned results and data reported by other
authors and ourselves, it was felt that a
demonstration of a consistent alteration in
sleep-wakefulness in " diencephalic" cats would
further document forebrain participation in the
control of sleep and wakefulness.
It is well known that barbiturates induce
EEG spindle burst activity in intact animals.
This effect has also been shown to occur in the
diencephalon acutely separated from both rostral
d caudal brain stem structures. Since it has
been claimed hat barbiturates do not induce
spindle activity in decorticate eats, it was
decided to reexamine their effects in the
"diencephalic" cat. Quite unexpectantly, it was
noticed that thiopental induced changes in the
sleep-wakefulness patterns. This effect
wasstudied in detail since it was interpreted as
a pharmacological interference witha
hypopthetical mechanism of the rostral brain
controlling sleep and wakefulness.
In summary, this paper is concerned with the
following aspects of "diencephalic" cats:
1) neurology and overt behavior;
2) sleep wakefulness;
3) EEG-behavioral correlations;
4) effects of thiopental on the EEG and
sleep-wakefulness.
....page 352-358
1. - Neurology and overt
behavior.
1. Locomotion and reflexes. - The
"diencephalic" cats were able to walk on the
second postoperative day. During the following
one and a half months they were extremely
hyperactive, their main usually for hours (a
maximum of 17 hours of, uninterrup ed walking
was recorded in one cat). Any attempt to stop
the cats only enhanced the strength of their
progression. In three cats, this tendency was so
vigorous that if stopped they would fight, hiss,
and growl, and when released, would jump
forward. Although the hyperactivity declined
progressively, they spent a large part of their
time restlessly standing, sitting, or crouching;
episodes of obstinate progression persisted in
relation to defecation or micturation until they
were sacrificed.
Some degree of locomotor ataxia, including
moderate "goose step "-like gait was observed
during the first two postoperative days. Later,
locomotion was slower, and clumsy and there was
a tendency toward ventroflexion of the head and
lowering of the spine. During the early
postoperative days, hyperextension of the legs
could be induced by suspending the cat by the
scruff of the neck or when the Magnus reflex was
tested in dorsal decubitus; however, there was
no extensor rigidity or hyperextension of the
neck when the cat stood or walked. Indeed,
stretch reflexes. appeared to be diminished in
these animals since the tendon jerks were not
exaggerated and patting the pelvic girdle or the
spine produced flexion of the limbs, thus
suggesting a weakness of the positive supporting
reaction. Curiously enough, this latter maneuver
always stopped the animal's ongoing movements.
On the other hand, the righting reflexes were
hyperactive. The cats struggled to recover their
upright position after being placed on the floor
on their flanks or when suspended from the
pelvis with the head hanging. In the cats which
lived for up to six months there was a marked
flexor rigidity such that when the cats were
suspended from a flexed elbow the spine arched
forward and the head and hind limbs flexed
strongly.
Tactile placing and hopping reactions were
absent and only a coarse placing of the forelegs
was observed in the long-term cats. Their
sitting position was awkward, in that the hind
legs were usually thrust forward between the
forelegs.
A few apparently purposeful movements were
occasionally observed; for example, they could
use their forepaws skillfully in an attempt to
reject the insertion of the eye pieces of the
feeding tube and this was accompanied by
avoiding movements of the head.
2. Reaction to external stimuli. -
During the first two months, the cats shivered
when they were changed to a room slightly cooler
than the vivarium, when placed upon cold
surfaces or when tubefed a cool meal. This
reaction, however, was not reflected by changes
in rectal temperature. The threshold to
nociceptive stimuli (pinprick, heat) was not
changed in the acute state however, in the
chronic condition pain sensitivity appeared to
be rather enhanced. Although olfactory stimuli
induced vigorous sniffing and searching, the
cats were unable to locate the stimulus source;
the olfactory behavior was absent in those cats
in which the olfactory tracts were ablated.
There were no overt signs of vision in"
diencephalic" cats. They did not show a
visual-palpebral reflex and in walking they
bumped into objects irregardless of their size
or brightness. In contrast to this apparent
blindness, however, the pupils reacted briskly
to changes of illumination, and even a very weak
light source, & g., a burning match,
produced pupillary constriction. A strong light
source always produced (after the third mouth) a
type of avoidance reaction in that the pupils
constricted intensely, the nictitating membranes
covered the eye and the head deviated away from
the source of illumination.
One of the most striking reactions to
external stimuli was the exquisite reactivity to
auditory stimulation. Subtle noisse triggered
brisk body movements with ocular arousal,
perkings of the ears and orientation of the head
toward the source of the noise; this reaction
usually rapidly habituated. After the third
month, a stronger, sudden sound, e. g., a
handclap, induced a startle reaction often
accompanied by hissing and growling. In two
cats, sudden, loud noises produced an escape
reaction with sudden, fast, slinky running.
3. Eating and licking. Licking and
swallowing occurred when food was placed in
front of the animal's nostrils. Tube feeding
apparently induced some type of conditioning, i.
e., the chronic cats reacted with salivation to
the introduction of the feeding tube but later
salivation occurred simply by handling the cat
at the customary feeding time.
In four of the five chronic cats,
spontaneous licking occurred. They often licked
their chests and paws with occasional attempts
to rub their face with few, weak, paw strokes.
This grooming activity, however, was completely
inefficient. In three cats after the fourth
postoperative month, licking the floor, other
cats and the walls often occurred, this activity
being triggered by disturbing stimuli.
4. Other behavior. - Two to three
months following decortication, the cats often
engaged in many iterative motor activities, e.
g., soft mewing, licking, or various movements
of the legs (scratching, kneading, etc.). These
activities were exaggerated by noises or by
handling to which some cats reacted with
continuous mewing. Stronger handling, like
brushing, or pressing their bladders out, often
triggered growling, hissing, loud guttural
mewing or more rarely, biting. Thus, a striking
behavioral feature of all chronic "
diencephalic" cats was their increased
irritability in response to minor environmental
changes.
The only " social" trait observed in these
cats was their tendency to congregate when
placed in the same corral. This behavior is
probably related to the finding that when placed
on a hard, cold floor, but having a small, soft
pad, the cats invariably were later found on the
pad. After 2-3 months there were other signs of
" awareness" to objects or surfaces; thus the
cat would stop or turn around after touching a
wall with its face (or even whiskers) or upon
reaching a border (i. e., the edge of a table)
with a paw. A similar behavior occurred when a
foot was wet or soiled; in this case the leg was
lifted and shaken vigorously as an intact cat
would do.
II. - Sleep-wakefulness
patterns.
Four stages were identified in the
sleep-wakefulness continuum of the
"diencephalic" cats. The cat was considered to
be awake when it either stood, walked, or
engaged in any other activity, e. g. licking or
mewing, or when it was quiet but kept its
eyelids open, nictitating membranes retracted,
eyeballs centered in the orbit and its pupils
dilated. The animal was judged to be drowsy when
it sat quietly or crouched with eyelids
half-closed, nictitating membranes protruding
variably and the pupils reduced and fluctuating
in size (although no smaller than 5 mm in width)
with the eyeballs exhibiting slow, often
dissociated movements. The cat was considered to
be in NREMs when it lay in a random or curled
position with the eyelids closed, nictitating
membranes protruding and eyeballs tending to
rotate inward and downward, with the pupils
smaller than 5 mm in width and exhibiting less
fluctations. Finally, the animal occasionally
lapsed into typical episodes of REMs with all
the behavioral and ocular features described for
this stage of sleep in intact and chronic
decerebrate cats.
After one month the "diencephalic" cats
progressively recovered their presomnic and
postsomnic postural patterns which further
helped to define the sleep-wakefulness stages.
Thus, crouching often occurred at the onset of
oculo pupillary sleep patterns and the typical
curled posture of intact cats was frequently
observed when the eyes exhibited a deeper sleep
pattern. Likewise, at the end of a sleep period,
the cats often stretched their limbs,
arched their backs and even yawned, as
intact cats do upon awakening.
There was a large reduction in the sleeping
time of all " diencephalic " cats. During the
first two sessions, NREMs time decreased to an
average of 17% of the total observation period,
or less than 50% of the time control cats spend
in this stage. REMS time decreased to 1,1% of
the observation time or less than onetenth of
the control value. Both NREMs and REMs time
further decreased and reached a stable level
only after the second month. During the last
four months, NREMs was under 5% of the total
observation time-or about 1/8 of the controls.
REMs time was even more markedly affected since
after the second month it decreased to an
average of 0.65% of the observation time or less
than 1/20th of the controls. In fact, REMs was
completely absent in ten out of 48 sessions
whereas NREMs was never absent. Drowsiness was
not significantly affected. The normal cyclic
distribution of drowsiness or of the remaining
NREMs or REMs could not be demonstrated. Feeding
did not affect the distribution of sleep
time.
Since the cats in the chronic state were
exquisitely reactive to noise and the noise
level in the observation room was not uniform
day and night, a comparison was made between
time spent in sleep from 8:oo AM to 8:oo PM and
from 8:oo PM to 8:oo A. M. It was found that the
cats slept about the same during the day (6.2%
NREMs and 0.8% REMs) as during the night (5.4%
NREMs and 1.0% REMs).
Two other features differentiated the sleep
of " diencephalic" cats from that of intact
cats: 1) the mean duration of REMs period was
shortes in " diencephalic " cats (4-1/2 mm) than
in intact cats (6-1/3 mm) (35); 2) the amount of
phasic muscular events during REMs was higher in
"diencephalic" than in control cats.
page 369
Discussion
2. Sleep-wakefulness. - Although
observations concerning sleep wakefulness in
decorticate animals have been reported
previously, several factors limit their
comparability with the present results. First,
in most cases the authors were only secondarily
interested in sleep. Secondly, REMs was not
known as a separate entity at the time many of
those experiments were performed. Thirdly,
although the extent of the decortication was not
always clearly stated, it appears that usually
only a neodecortication was done. Finally,
quantitative studies of the sleep-wakefulness
patterns were not performed in the earlier
experiments.
Hyperactivity has been a common finding in
decorticate dogs. Kleitman and Camille reported
a predominance of locomotor activity in
decorticate dogs but they did not provide any
figures concerning the actual sleeping time of
their animals. Hypercativity after decortication
has been likewise described for cats and in a
more sleep-oriented study, it was found that
decorticate cats sleept approximately eight
hours whereas intact cats slept for 18-20
hours.
Motor hyperactivity in decorticate animals
can be interpreted as the result of a "release"
phenomenon. The question then arises as to why
this hyperactivity decreased after one to one
and a half months. The reasons are probably
complex and may involve anatomical
(degenerative) alteration of the subcortical
structures originally "released" by
decortication, compensatory neuronal processes
and even prolonged sleep-deprivation.
On the basis of their studies, Mettier et
al. questioned the existence of hyperactivity in
decorticate animals. An important methodological
difference which may explain the discrepancy
between their study and the present findings is
that their dogs were decorticated in several
stages over a period of six months. It has been
shown that the effect of a CNS lesion is greatly
attenuated or changed when it is performed in
several steps.
There appears to be only one extensive EEG
and behavioral study concerning both REMS and
NREMs in decorticate animals. In that study,
NREMs was reported to be almost completely
absent whereas REMs was within the normal range
(15-20% of the observation time).
The present study appears to be the first
demonstrating a permanent, pronounced reduction
in both REMs and NREMs following a rostral brain
lesion. During the first postoperative month,
the insomnia might be attributed to an indirect
effect of the animal's motor hyperactivity.
However, since the hyperactivity decreased
following the second month while the
sleeplessness did not, the insomnia is probably
a primary phenomenon. An increased sensory input
does not appear to be a causative factor either
inasmuch as there was no difference in the
sleep-wakefulness pattern of the cats when
studied under different levels of environmental
noise (nighttime versus daytime study).
Unlike the present experiments, Jouvet's
study was performed in cats with the limbic
system and striatum essentially intact.
Furthermore, it has been repOrted that there is
a permanent behavioral activity in
"diencephalic" cats and rats, whereas
neodecorticate cats are inactive and
neodecorticate rats are only moderately active.
Therefore, it appears that the presence of the
striatum and/or rhinencephalon is important for
a normal sleep-wakefulness alternation.
The fact that chronic cats with high
complete mesencephalic transection do not
manifest a marked decrease in either REMs or
NREMs suggests that rostral structures do not
exert much control over caudal brain stem sleep
mechanisms. However, the present finding in
"cliencephalic" animals necessitates a revision
of this concept. Accordingly, we postulate that
in the intact animal, both enhancing and
suppressing rostra.l brain influences impinge
upon caudal brain stem sleep mechanisms and
modulate their function in a balanced manner.
Consequently, mesencephalic transection, by
completely removing both types of influences,
would not induce too large a disturbance. On the
other hand, a functional imbalance might occur
when only some parts of the rostral brain are
removed. More specifically, we postulate that in
"diencephalic" cats, a net loss of
sleep-enhancing influences descending upon the
brain stem from either the neocortex, striatum,
rhinencephalon, or from all of these areas
results in sleeplessness. The sleep-suppressing
effects may hypothetically be ascribed to the
hypothalamus and/or subthalamus. There is
evidence that these structures posses arousal
properties and both structures were undisturbed
by surgery in our experiments. Moreover, the
hypothalamus has been demonstrated to remain
functional even after complete isolation. The
hypothalamus may primarily favor wakefulness
rather than directly. supress sleep; if this is
the case, our basic hypothesis of an imbalance
among elements of the descending rostral brain
control would still be tenable.
At least two forebrain areas - i. e., the
caudate nucleus and the orbitofrontal cortex -
ablated in the present experiments have been
demonstrated to be involved in sleep, EEG
synchronization and behavioral inhibition. The
basal forebrain area, which was not directly
lesioned in the present cats, also shares these
properties and, according to Clemente, is the
main component of a descending synchronizing
system, which acts reciproally with. the
ascending reticular activating system to
regulate .... "the level of cortical activation
or synchronization.....". The lesioning of the
above forebrain areas most probably contributes
to the insomnia of the "diencepbalic" cats in
the present study However, mainly on the basis
of the lack of any striking insomnia in cats
with high mesencephalic transection, we propose
that the descending modulatory action of the
rostral brain consists of both activating and
deactivating influences rather than of a
descending deactivating system oppossing the
action of an ascending activating system.
