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The subcommissural organ.

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THE SUBCOMMISSURAL ORGAN
GORDON J. GILBERT
Department of Anatomy, N e w Pork University College of Yedioine
N e w Pork, N . P.
FIVE FIGURES
One of the most archaic structures in the body, the subcommissural organ occurs throughout the vertebrate series,
from the lowest fishes to the primates (Sargent, '00, '01;
Nicholls, '17; Jordan, '19). Situated at the oral end of the
posterior commissure, the organ gives rise to fibrils which
unite to form Reissner's fiber, a delicate thread extending
down the center of the spinal canal. Since the time of Sargent 's
hypothesis (1900) that the sabcommissural organ and Reissner's fiber constitute a mechanism for the facilitation of optic
reflexes, there has been considerable disagreement concerning
the function of this strangely persistent structure. Recent
histochemical studies (Leduc and Wislocki, '52 ; Wislocki and
Leduc, '52a, '52b, '54) have indicated that the organ is secretory and exhibits a high level of enzymatic activity. Preliminary experiments by the author, in which the organ was electrically ablated, have suggested a role for the subcommissural
organ in water-electrolyte metabolism. The experiments presently described represent an extension of these studies in an
attempt to ascertain more clearly (1) the effects of electrocoagulative ablation of the subcommissural organ, relating to
the water metabolism; and (2) whether the organ manufactures a secretion of physiological significance.
MATERIALS AND METHODS
(A) Forty-six white rats, of both sexes, weighing 200 to
250 gm, were used. The daily consumption of food and water
253
254
GORDON J. GILBERT
was followed in each rat for at least one week prior to operation. Such intake in a rat under controlled environmental
conditions is quite regular, a typical range of water consumption over a 5 day period being 25 to 30ml per day.
The operation was completed within 20 minutes. The animal
was anesthetized (ether) and its head placed in a stereotaxic
instrument. A small opening was then drilled in the midline of
the skull over the midbrain, a needle inserted for a distance
of 2.5 to 3 mm by a micromanipulator, and electrocoagulation
performed. The skin was sutured, and the animal returned to
its cage.
Each rat underwent either one or two operations (two when
the first was without any observed effect). Post-operatively,
the animals were observed daily for at least two weeks, where
possible. Often, however, the fall in water consumption was
such that the rat’s weight-loss became severe within 4 or 5
days, necessitating earlier sacrifice.
The heads were fixed in formalin, decalcified, celloidin embedded, sectioned transversely (50 p), stained with thionin,
and studied microscopically. The presence or absence of the
subcommissural organ was noted, as were the size and location
of the lesion.
(B) Fourteen white rats, of both sexes, were used. Water
consumption was followed for at least one week, until the daily
water intake had become regular. These rats received subcutaneous injections of subcommissural organ extract prepared
as outlined below.
The brain of another rat was removed, and the subcommissural organ quickly (one minute) dissected out. This dissection was facilitated by the relative prominence of the posterior
commissure in the r a t ; a portion of the posterior commissure
was removed together with the subcommissural organ. The
total operational procedure was completed within 45 minutes.
The subcommissural area was next mashed, mixed with 2 ml
of isotonic saline solution, and injected subcutaneously into
one of the observed rats. As the control, a piece of cerebrum
THE SUBCOMMISSURAL ORGAN
255
from the same (donor) animal, and of approximately equal
size, was mashed, mixed with 2 ml of isotonic saline, and subcutaneously injected into a second rat. Animals receiving injections were observed during the following days for any alteration in water consumption.
One operation was performed in the morning; the others
were begun in the afternoon ( 1 4 ~ . ~Since
. ) . rats do their
heavy drinking nocturnally, daily water intakes were measured at 1 0 a . ~each
.
day.
RESULTS
(A) Ablation of the subcommissural organ. I n this first
series, the rats recovered quickly from the operation, and within an hour returned to normal behavior and activity. Any animal which, following operation, appeared sickly or in any way
incapacitated was not included in our list of “successful operations.” Sixteen such rats, showing some signs of weakness,
“emotionalism” (aggression), or disability (limp, paralysis)
during the post-operative period, were eliminated from the
experiment.
The 30 animals remaining were found each to fit into one of
the following 5 categories :
Category I : Immediate, lasting post-operative fall in
water consumption ; microscopic examination revealed
subcommisural organ completely destroyed. 13 rats.
Category I1 : “Controls.” Water consumption unaffected
by the operation. Microscopic examination revealed
subcommissural organ intact. 8 rats.
Category 111: Water intake increased on the day of the
operation, then normal. Subcommissural organ found
intact, but lesion very close to it. 2 rats.
Category IV : Water consumption initially low following
the operation, returning to normal levels within a few
days. Microscopic examination revealed subcommissural organ partially destroyed. 6 rats.
Category V: Water intake normal for several days following the operation, then diminished ; subcommissural
organ intact. 1rat.
256
GORDON J. GILBERT
Figure 1describes the post-operative course of two animals
placed in category 11. One of these rats received one operation,
the other, two. I n each case, it will be noted that following the
operation, water intake remains within normal limits for that
animal, either rising slightly or falling a small amount. The
subcommissural organ was found to be spared in each animal.
I n figure 2 is represented the daily water consumption of 5
category I rats. Note that in each animal post-operative water
intake is consistently subnormal, in rats of excellent appear-
2 40
animal 3c
I
I
1
I
I
I
I
0
-
cQ
s3
401
OPERATION
I
OPERATION
s
animal 9b
0
I
I
I
I
1
3
5
7
I
I
I
9 1 1 1 3
DAYS
Fig. 1 The daily water consumption of two rats receiving the operation. Postmortem examination revealed subcommissural organ intact.
ance. Individual variations are seen among the animals, 4 rats
(nos. 7d, 2c, 3d, and 4c) having almost no post-operative intake, while the 5th (no. 11)maintains a moderate, persistently
subnormal water consumption over a period of three weeks.
Post-mortem examination revealed the subcommissural organ
to be completely destroyed in each rat.
Plate 1was prepared to determine more decisively the role
of the subcommisural organ per se, apart from other, adjacent
structures also involved in the various lesions which we pro-
257
THE SUBCOMMISSURAL ORGAN
duced. It portrays all lesions associated with a drastic and
persistent post-operative fall in water consumption. Most of
these lesions are centered about the aqueduct, and even the eccentric lesions involve it. The shaded zone in plate 1 is the
“common denominator” for ALL these lesions, and is thus
the area which we find e.ssentia1for normal water consumption.
There are but two structures in this zone: a portion of the
posterior commissure, and the subcommissural organ.
c
OPERATION
0PERATION
20
SACRIFICE
SACRIFICE
animal 7d
0
2
4
animal 2c
6
8
10
~
2
4
6
8
1
0
L
SACRIFICE
SACRlFICE
10
anirnal3d
0
0
2
4
6
8
0
0
2
4
6
8
D A Y S
Fig. 2 The daily water consumption of 5 operated rats. Histological examination of the brains showed subcommissural organ completely destroyed.
258
GORDON J. GILBERT
(B) Table 1lists the results of the 9 experiments in which
an extract of subcommissural area (or, as the control, of a
single piece of cerebrum) was subcutaneously injected into another animal. F o r reasons to be subsequently stated, we have
separated the 8 experiments carried out in the afternoon from
the one performed in the morning. A fall in water intake of
about 20% occurred in 6 of the 8 rats receiving injection of subcommissural area. Not one of the animals receiving the control
TABLE 1
T h e effect on water consumption achieved by t h e subcutaneous injection of t h e
szcbcornmisissural area or of cerebrum (control) of t h e same rat. Ezpressed as p e r centage deviation f r o m the mean of t h e contror period.
~~
EXPERIMENT
1
2
3
4
5
6
7
8
Total
Mean deviation from
mean of control periods :
Morning operation
9
SCO-INJECTION
CONTROL I N J E C T I O N
%
%
-23
-24
+7
- 11
- 20
0
-6
+5
- 20
- 9
- 20
- 20
- 10
- 12
- 147
-34
- 18
-4
+5
-6
-7
- 11
injection of cerebrum had a deviation of this magnitude. Indeed, in the afternoon group, approximately 4i times the control deviation of - 4% (the latter may well be considered
within the normal limits of day to day variability of water
consumption in the rat) was obtained following the subcutaneous injection of subcommissural area.
The daily water consumption of the 8 sets of rats is presented graphically in figure 3, along with that of a ninth rat
into which extracts from two subcommissural areas were in-
259
THE SUBCOMMISSURAL ORGAN
jected. The uniform pattern of reduced intake following injection of the subcommissural area is in marked contrast to
the random behavior following the control injections. The
animal receiving the extract from two subcommissural areas
is the one showing the lowest post-injection intake on the
z 4 0 -3 35 30 ' 25 45
s
:
2
0
i2
- I
0-
I
I
I
I
I
I
I
I
I
I
DAYS
Fig. 3 I n ( I ) the subcommissural area is injected subcutaneously after 6 control days. I n (11) cerebrum from the same donor rat is subcutaneously injected.
Nine such experiments are represented.
graph (26 ml/day), and remaining at that level for two days
rather than the usual one day.
Figure 4 is a graphic illustration of the water intakes of
three animals that received more than a single injection. One
can thus compare the effects of subcommissural area and cerebrum, on subcutaneous injection into the same rat. Note that
each injection of subcommissural area is followed by a record
260
GORDON J. GILBERT
Fig. 4 Daily water consumption of three rats receiving more than one subcutaneous injection.
Injection S -Inject subcommissural area subcutaneously.
Injection C -Inject
control (cerebrum) subcutaneously.
low in water consumption. The control injections are followed
by random changes in water consumption, in no case outside
the normal limits established during the pre-injection control
period. Also noteworthy is the consistency of results obtained
in the same animal. In animal no. 6, the first injection of subcommissural area resulted in a sharp fall in water intake to
27 ml; the second injection, in an equally precipitous drop to
28 ml.
DISCUSSION
Category I, the largest group of rats, strongly indicates a
correlation between the absence of the subcommissural organ
and decreased water consumption by the rat. Electrocoagulative ablation of the organ was in each instance associated'with
THE SUBCOMMISSURAL ORGAN
261
a sharp and persistent reduction, in wate.r intake. It may in4
deed be significant that Wislocki has found only four tissues in
the “brain’ which stain with Gomori’s chrome alum hematoxylin stain (originally used for selective staining of the
insulin-producing Beta cells of the pancreas). These tissues
are elastic tissue, the posterior pituitary, the subcommissural
organ, and Reissner ’s fiber (a protoplasmic extension of the
subcommissural organ down through the spinal canal). The
secretion of the posterior pituitary has been shown to consist
of octapeptides concerned with water metabolism at the output
level. Evidently the subcommissural organ, too, plays an important role in the water economy of the body, but at the intake
level. The site of thirst, the mechanism delicately balancing
intake against loss of fluid, has been sought but not disclosed
in several parts of the body, including mouth and stomach
(Holmes, ’50; Adolph, ’50). Apparently this elusive controlling factor is sssentially related to a small organ located beneath the posterior commissure of the brain.
Although only two rats fall into category 111, the transient
rise in water consumption following the operation suggests
that the thirst mechanism of the rat has been in some manner
stimulated. I n each case, the lesion was very near, but did not
damage the subcommissural organ. An electrical or postoperative stimulation of the organ, resulting in a short term
of excessive activity is postulated as the operative mechanism.
The second experimental procedure was designed to ascertain whether in the subcommissural area there is produced a
secretion having hormonal activity, and having some influence
on the water metabolism. Secretory activity by the organ was
strongly indicated by Wislocki’s histochemical work, and the
specific staining with Gomori’s stain offered hope for finding
an endocrine product similar to that produced by the Beta cells
(a protein of low molecular weight) or by the neurohypophysis
(polypeptide).
It will be noted that on the day of the subcutaneous injection
of subcommissural area, there occurred a decrease in drinking
averaging about 2070 of the mean of the control period. The
262
GORDON J. GILBERT
“control” group, however, tended to remain within the limits
defined during the control period. Reference to figure 3 further reveals a tendency toward increased water consumption
on the second day following injection, a n effect readily interpreted as a compensation by the animal’s own subcommissural
organ tending to reestablish normal fluid equilibrium.
I n experiment (A), the subcommissural area was found to
be essential for normal water metabolism. Experiment (B)
suggests that this function is endocrine in nature. Water
metabolism (and with it, electrolyte metabolism) is a delicately
balanced system of economics. This balance is vital among the
body’s homeostatic defenses. Hormones, adrenocortical and
neurohypophysial, are known to govern outflow. Evidently intake, too, is so regulated, and by a structure of such consequence that it exists throughout the vertebrate series. We
postulate that the subcommissural organ, perhaps regulated
by the osmotic pressure of the blood or cerebrospinal fluid,
secretes quantitatively a hormone which, acting on end-organs
presumably neural in nature, alters water consumption and
thus affects the fluid composition of the body.
We conclude from experiment (A) that the effect on drinking of the functioning subcommissural organ (or subcommissural gland, as we now feel it should be named) is probably
facilitative. We interpret the actual fall in water intake observed following the subcutaneous injection of the gland in
experiment (B) as an overcompensation by the animal’s own
subcommissural gland, antagonizing the tendency of the injected subcommissural area to i m r e a s e water consumption.
Two points appear pertinent in this connection: 1. The spike
in drinking seen in the graphs on the second day following the
injection; 2. I n the one rat receiving a morning injection (see
table l),there was no effect on water intake as observed the
following morning. Apparently during the first 15 to 20 hours,
the total effect achieved by the subcutaneous injection of a
single subcommissural area is a depression of intrinsic subcommissural activity, with lowered water intake but given a
THE SUBCOMMISSURAL ORGAN
263
full 24 hours the animal’s own subcommissural gland adapts
so as to compensate for this period of de,pressed activity.
SUMMARY
The subcommissural organ, long an enigma, has recently
been described as a site of possible secretory activity. The
work presented here, involving (1)the electrocoagulative ablation of the subcommissural organ, and (2) the subcutaneous
injection of its extract into rats, indicates an important endocrine function of the organ in water metabolism, probably as
an essential component of the mechanism for the control of
thirst. The microcoagulation of the subcommissural organ
leads to an immediate, drastic, and persisting fall in water consumption, while the effect of its subcutaneous injection into
rats strongly suggests distinct hormonal activity.
ACKNOWLEDGMENTS
The author wishes to express his sincere thanks to Dr.
Pinckney J. Harman for his generous support and wise counsel
during the course of the experiments. Dr. Harman and Professor Dona1 Sheehan have given much helpful advice during
the preparation of the manuscript. The author is also indebted
to Dr. Wilbur H. Sawyer f o r his kind aid since the initiation
of these studies, and to Mary Lorenc for the preparation of
the plate and figures.
LITERATURE CITED
ADOLPH,E. F. 1950 Thirst and its inhibition in the stomach. Am. J. Physiol.,
161: no. 3.
IIOLMES,
J. H., AND M. I. GREGERSEN1950 Observations of drinking induced by
hypertonic solutions. Am. J. Physiol., 162: no. 2.
JORDAN, H. 1919 Concerning Reissner’s fiber in teleosts. J. Comp. Neur., 30:
217-22 7.
LEDUC,ELIZABETH
H., AND GEORUE
B. WISLOCKI 1952 The histochemical localization of acid and alkaline phosphatase, non-specific esterase and suecinic dehydrogenase in the structure comprising the hematoencephalic
barrier of the rat. J. Comp. Neur., 97: 241-279.
R-ICHOLLS, G. E. 1917 Some experiments on the nature and function of Reissner ’s fiber. J. Comp. Neur., 27 :117-200.
264
GORDON J. GILBERT
SARGENT,
P. E. 1900 Reissner’s fiber in the canalis centralis of vertebrates.
Anat. AT., 17: 33-34.
1901 The development and function of Reissner’s fiber and it8
cellular connections. P.A.A., 36 :443-452.
TVISLOCKI, G. B., AND E. H. LEDUC 1952% The cytology and histochemistry of
the subcomrnissural organ and Reissner’s fiber i n rodents. Anat. Rec.,
11.2: 469 (abstract).
195213 The cytology and histochemistry of the subcommissural organ
and Reissner’s fiber i n rodents. J. Comp. Neur., 97: 515-544.
1954 The cytology of the subcommissural organ, Reissner’s fiber,
periventricular glial cells, and posterior collicular recess of the rat ’s
brain. J. Comp. Neur., 101 : 283-310.
J. GILBERT
PLATE 1
A generalized transverse section through the midbrain at the level of the subcommissural organ (central, blackened structure at the do]
sal margin of the aqueduct), outlining the lesions present in animals showing post-operatively a severe, persisting deficit of water consumption. The darkened area surrounding the subcommissural organ is the “common denominator” for all these lesions.
GORDON
THE SUBCOMMISSURAL ORGAN
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