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Appetitive behavior in rats after circumsection of the hypothalamus
Phvsiolog.v and Behavior. Vol. 3, pp. 221-226. Pergamon Press, 1968 Printed in Great Britain
Appetitive Behavior in Rats after Circumsection of the Hypothalamus' GAYLORD
D. E L L I S O N
Department of Psychology, University of California, Los Angeles (Received 2 June 1967) ELLISON,G.D. Appetitivebehaviorin rats after circumsectionof the hypothalamus. PHYSIOL.BEHAV.3 (2) 221--226, 1968.-Hypothalamic islands were made in rats by means of a knife which was inserted down into the brain and then rotated so as to sever the neural connections of the hypothalamus with the rest of the brain while leaving intact its connections with the pituitary gland. Rats are aphagic and adipsic after the major pathways from the hypothalamus are cut, but their syndrome is similar to that seen in decerebrate rats rather than like that in rats with lateral hypothalamic lesions. These results stand in contrast with those obtained from cats, who can show eating behavior immediately after similar neural isolation of the hypothalamus. Hypothalamus
Adipsia
Aphagia
Rats
had been malleted flat, honed sharp, and bent into shape, and was housed in a shaft made of 20 gauge hypodermic tubing so that it could be rotated while in the brain, cutting the sides and top of a cylinder 7 mm in dia. and 1.5 mm deep.
ALTHOUGH the hypothalamus is generally considered to be essential for the occurrence of spontaneous motivated behavior in an integrated form, there have been few studies of the behavioral capabilities of animals lacking an entire hypothalamus but with the rest of the brain intact. This is undoubtedly due to the technical difficulties involved in making extensive lesions of this area. It has recently proved possible to study animals in which an island of hypothalamic tissue has been created by means of a knife initially inserted down through the brain along the midline and then rotated so as to sever the neural connections of the hypothalamus with the rest of the brain while leaving intact its connections with the pituitary body. In a recent study using this revolving knife technique [5], it was found that cats even though deprived of neural influences from the hypothalamus showed a wide range of aggressive and appetitive behaviors, and in particular voluntarily ingested food within minutes after lesioning. This result was unexpected since it is widely believed that voluntary eating and more generally hunger depend upon the integrity of a lateral hypothalamic "hunger" center which is normally held in check by a medial hypothalamic "satiety" center. Because many of the studies which have given rise to this conception have used rats as subjects, further experiments were undertaken to study feeding behavior in the rat following neural isolation of the hypothalamus. Previous studies using the revolving knife technique on rats have been confined to the use of a small knife designed to deafferent the pituitary and medial hypothalamus alone [7, 8].
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FIG. 1. The knife used to produce the lesions, as described in the text. The blades, one of which faces the viewer, were sharpened under a microscope until they would break the skin when stroked across the experimenter's finger.
METHOD
The lesions were produced by means of the knife shown in Fig. 1. It was made from stainless steel of 0.020 in. dia. which
XThis research supported in part by NIH grant MH 12,841. I thank F. Helmholz, D. Parker, and H. Reznick for assistance in conduction of these experiments, R. Gorski for advice in construction of the knife, and D. Novin for histological assistance. 221
222
ELLISON
The rats were placed in a stereotaxic instrument like that described by deGroot [4] in order to make the lesion. A bone flap about 3 × 5 mm was removed along the midline with care taken not to rupture the superior saggital sinus, and the dura was cut immediately adjacent to the sinus. The knife, the shaft of which was fixed at 70 ° to horizontal in the saggital plane (the top of the shaft being most posterior), was then lowered into the brain immediately adjacent to the sinus. When the blade of the knife had passed the level of the sinus, the knife was moved medially so as to be exactly along the midline and then ventrally (along the angle of the shaft) until the anterior tip of the knife rested at AP + 9.9, H-1.3, and L 0. The knife was then rotated several times in both directions, returned to its original position with the blade facing anteriorly, and retracted in the same manner it had been lowered. In the preceding description the final position of the knife is given in deGroot coordinates. In actual practice the final position of the knife was arrived at by placing the hub of the knife at stereotaxic zero with the shaft at the 70 ° angle to horizontal and then calculating coordinates so that the knife was moved anteriorly 7.75 mm and dorsally 4.75 mm along the angle of the shaft. The knife (facing anteriorly) is shown in position using these latter measurements in Fig. 2 with the rat oriented in the stereotaxic instrument.
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29c of Krieg) had been damaged unilaterally when the knife was inserted. The anterior half of the corpus callosum had been sectioned by the knife as it was lowered, as was the hippocampal commissure. There was considerable damage to the medial and lateral septal nuclei and some damage to the preoptic area and to the most anterior parts of the paraventricular and reuniens nuclei of the thalamus. Eating behavior returned in such control animals on the first or second day following surgery and appeared normal thereafter. In 7 animals in which the knife was rotated, the knife cuts typically started anterior to the optic chiasm, and at the level of the anterior commissure extended out to include all of the medial and much of the lateral preoptic area but usually failed to extend completely to the base of the brain. At the level of the ventromedial nuclei of the hypothalamus, the island included all of the lateral hypothalamus. The lesion remained as far lateral as the internal capsule more posteriorly and extended dorsally to include part of the ventral thalamus. The island ended just posterior to the mammillary bodies. Figure 3 presents four sections from an animal which survived for 29 days following surgery. In this animal the knife cuts extend ventrally to the base of the brain in the posterior hypothalamus but stop short more anteriorly, a pattern which varied from animal to animal. Because the main efferents from the hypothalamus generally course in either a dorsal or a posterior direction, the main outflows from the hypothalamus have been eliminated in this animal. Figure 4 shows an enlarged segment from one of the sections in Fig. 3 so that the lesion can be seen more clearly. Sections from five other animals are presented in Fig. 5. In assessing the extent to which the lesions have effectively created an animal in which the neural influences from the hypothalamus have been eliminated, attention should be directed toward the degree of interruption of fiber systems to and from the hypothalamus rather than the extent of destruction p e r se. I n
TABLE EXTENT OF DAMAGE
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TO THE MAJOR HYPOTHALAMIC PATHWAYS IN EACH OF THE ANIMALS.
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Animal No.
FIG. 2. The knife shown in position and facing anteriorly. The diagram represents a rat held in place in the stereotaxic instrument.
HI2 H13 H16 H19 H20 H22 H25 Dorsal longitudinal fase. t t tt tt tt ¢t tt tt Columns of fomix tt tt tt tt tt tt tt Habenulopeduncular
Postoperatively the animals were housed in an incubator. The temperature of the incubator was regulated so as to maintain the rectal temperature of the rats at about 34C °. Each animal had constant access to a liquid diet, water, and lab chow pellets, the edges of which had been ground smooth so that it was possible to detect any attempts to eat them. The liquid diet, which was similar to that used in previous studies, was a mixture of 270 ml of Sego or Nutrament brand liquid diet (chocolate flavor), 30 g sucrose, 15ml. Kaopectate, and 0.4 cc formaldehyde as a preservative.
Inferior thalamic peduncle Mammillary peduncle Mamrnillothalamictract Mammillotegmental tract Medial forebrain bundle: rostrally caudally Periventricular thal-hypothal, Stria medullaris Stria terrninalis Ventral amyg-subeortical
tract
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*
RESULTS
In 4 control animals in which the knife was lowered into position and withdrawn without being rotated, subsequent histology revealed that the midline cortex (parts of areas 4 and
¢tindicates bilateral destruction; "]'indicates unilateral destruction; indicates not destroyed; *indicates that it was not possible to determine amolmt of destruction because of an error in histology.
r
II
FIG. 3. Photographs of 4 sections from animal H22. Section " a " is at the level of the optic chiasm, sect/on "'b" at the level of the ventromedial nuclei of the hypothalamus, section "c" at the posterior tip of the ventromedial nuclei, and section " d " at the level of the mammillary bodies. Paraffin sections with cresyl violet stain.
( 1 o ¢ i ~ pa~ e
222)
FIG. 4. An enlarged segment of section "c" in Fig. 3. The cut can be seen extending bilaterally to the base of the brain.
FIG. 5. Sections showing the lesion in 5 other animals. From the top down, the sections are from animal H25, H20, HI3, HI2, and HI6. Paraffin sections with cresyl violet stain.
APPETITIVE BEHAVIOR AND HYPOTHALAMIC CIRCUMSECTION Table 1 the extent of damage to the major afferent and efferent pathways of the hypothalamus is listed for each animal. In order to better present the pattern of destruction of structures other than the hypothalamus, drawings corresponding to sections from the deGroot atlas were made and the lesions of three rats projected upon these figures. The results are presented as Fig. 6. As was found previously using the revolving knife technique on cats, chronic animals prepared in this manner frequently are found to have expanded ventricles, and the wound caused by the knives also frequently appears to have been expanded. This is why the size of the lesions in Fig. 6 often do not appear to correspond exactly to those in Figs. 3 and 5. These six animals were observed postoperatively for periods ranging from 20 to 33 days; one other animal was
223
hind paw of a lesioned rat was pinched. Because the lesions were near, and sometimes encroached upon, the medial lemniseus, further experiments were performed to determine if taste impulses could still be recorded at the cortex after lesioning. It was found that the cortical evoked potential elicited by stimulation of the ninth cranial nerve after sectioning of the pharyngeal branch was not destroyed by the hypothalamic island lesion. Auditory startle reflexes were present in these animals but it was not determined whether or not these animals were blind, although a number of attempts were made to do so. The behavior of these rats was consistent from animal to animal. By the third day postoperatively they had recovered sufficiently so that a number of behaviors could be observed. They were not comatose, but rather could usually be observed
FIG. 6. Reconstructionsofthelesionssuperimposed ondrawingsrepresenting sections from deGroot. The column on the left presents the lesion in H22, the column in the center is from animal H20, and the column on the right represents the lesion in animal HI9. The top row of drawings are from a section through the optic chiasm, the second row through the ventromedial nuclei of the hypothalamus, the third row through the mammiUary bodies, and the last row just posterior to the rnammillary bodies. The lesion in each case is represented by the solid dark area.
sacrificed 9 days after lesioning. Immediately upon lesioning the body temperature of these animals fell drastically, and so they were housed in an incubator which was thermostatically regulated. As the animals recovered from the lesion it was possible to gradually lower the temperature of the incubator, but no animal ever reached the point where it could be left at room temperature. Because the operation to isolate the hypothalamus also produced some thalamic damage, it was necessary to demonstrate that these rats were not functional decerebrates. It was found that tactile placing reactions, which are absent in decerebrate rats [12], were present bilaterally in all rats. Olfactory reflexes were present to pyridine, although trigeminal involvement could not be ruled out. A synchronizer E E G recorded from the cortex desynchronized rapidly when the
sitting in their cages grooming. When picked up roughly or pinched on the flank, vigorous escape efforts were observed, including squealing, struggling, and attempts to bite the experimenter's hand. When placed on the floor after such escape attempts the rat would run from the experimenter. Polyuria was not observed in any of these animals, indicating that the hypothalamic island was functioning [3, 13]. A Richter drinking tube containing liquid diet was constantly available to each of these animals. The high ambient temperature of the incubator increased evaporation loss, so each animal's daily diet intake was measured by comparing the loss from the animal's tube with that from a control tube. Using this measure, none of the animals postoperatively drank any liquid diet while in the home cage. The same was true of water intake, which was also compared with a control tube.
224 The laboratory chow pellets never showed any evidence of gnawing. The aphagia and adipsia were in contrast to the behavior of" these rats when hand-fed. When an eyedropper filled with liquid diet was brought to the lips of a lesioned rat, it would frequently open its mouth, turn its head toward the dropper, and grasp the dropper with its teeth. Care was taken to insure that the dropper was not inserted deep into the rat's mouth. Rather, the tip was normally inserted only 2-3 mm into the mouth. Diet then injected into the rat's mouth was immediately swallowed while the rat held the dropper with its front paws. Daily feedings of 15 cc's of the liquid diet were routinely given in this manner. In order to insure that this fluid was really being consumed, the rats were weighed both before and after daily feedings. After the first 3 cc's of diet the average weight gain of 4 rats was 2.8 g, and after 15 cc's the average weight gain was 13.1 g. These data are for the last 4 rats, from whom the most data were collected, but comparable data were collected from the other rats as well. A similar acceptance of food was observed when the rats were placed on a solid surface and bits of milk chocolate or lab chow were placed against their lips. A lesioned rat would grasp the food with a paw, gnaw on the food, and consume it. Similar behavior was also observed, however, when inedible objects were brought to the rat's lips. A pencil would be repeatedly grasped with the paw and gnawed, although unpleasant tasting substances were rejected. These rats, then, showed feeding reactions identical to those reported for decerebrate rats [12]. It should be noted that these feeding reactions were not merely aggressive attempts on the part of the rats to bite at anything placed in their mouths. The pattern of feeding reactions reported could be observed only during times when the rats were relatively calm and consisted principally of repetitive lapping movements with frequent swallowing and little biting. The experimenter's finger could be safely inserted into their mouths during feeding sessions; this resulted merely in a gnawing on the finger without the drawing of blood. Animals can be forced to swallow food by manipulation of aggressive reactions, but the pattern of swallowing in such a case is entirely different. It occurs during vigorous struggling to escape. Such swallowing also occurs mainly when the mouth is very full and food is on the back of the tongue, and is invariably accompanied by biting at the utensil used to place the food in the mouth. When struggling occurred in the rats reported here (this occurred more frequently just after lesioning, as these animals had not been pretamed), the rat was placed on the floor and calmed rather than having diet forcibly injected into the mouth. Some liquid diet was inevitably spilled while feeding these rats with the eyedropper. This diet dried on their fur, and most of the spontaneous activity observed in these rats consisted of grooming. Grooming attempts also accounted for most of the interruptions in hand feeding. Aphagia and adipsia also occur after smaller electrolytic lesions of the lateral hypothalamus alone, but previous descriptions of such rats have indicated that they will not readily accept food placed directly into the mouth [9, 11]. In order to better compare feeding reactions of lateral hypothalamic rats with hypothalamic island rats, bilateral electrolytic lesions of the lateral hypothalamus were attempted in 12 rats. In 5 of these rats long term aphagia and adipsia were successfully obtained. These 5 rats, which were apparently healthy after lesioning but subsequently died from starvation even though dry food, liquid diet, and water were available,
ELLISON consistently rejected the liquid diet when placed in the mouth. These animals would typically push the eyedropper away with the paws when it was brought to the mouth and viciously bite the dropper when it was forced into the mouth. The head was turned from side to side, apparently in attempts to escape from the dropper. When diet was forcibly injected into the mouth, some would initially be swallowed (this amount varied from 0.3-1.5 cc in different rats) but then the rat would stop swallowing and allow any further diet to run out of the mouth. The average weight gain after 3 cc's were injected into their mouth was 0.9 cc, some of which was spilled diet on the rat's fur. This value was significantly less (p <0.05) than the comparable weight gain for rats with a hypothalamic island. A number of rating scales were devised in an attempt to further quantify the differences in food acceptance between the hypothalamic island and the lateral hypothalamic lesion groups. None of these were consistently successful, chiefly because of the wide variety of behaviors used by different animals with lateral hypothalamic lesions to avoid the dropper. A double-blind control experiment was also impracticable because of other obvious differences in behavior between the two groups. However, all of the weight gain after feeding data reported here were obtained by two independent observers, both of whom were technicians and neither of whom understood the nature of the experiment. Each of these observers fed both hypothalamic island and lateral hypothalamic lesion animals. Each used terms similar to "acceptance" and "rejection" to describe the feeding behavior of the two respective groups. The remainder of the animals with lateral lesions can be divided into two groups. Five animals accepted diet from the eyedropper after lesioning, and voluntary feeding returned in each of these animals from two to six days after lesioning. Two other animals were comatose just after lesioning, and these animals did not reject liquid diet placed in their mouth while they were comatose. One of these animals died a week after lesioning; the second recovered spontaneous activity and began rejecting food until it died on the 15th postoperative day. DISCUSSION
Rats after circumsection of the hypothalamus are aphagic and adipsic, behaving toward food and water exactly as do deeerebrate rats. In some of these rats almost all of the tracts to and from the hypothalamus have been sectioned (cf. Table 1), and their behavior therefore is probably representative of rats after the elimination of neural influences from the hypothalamus. Other rats subjected to control lesions which cause damage to the midline thalamus and septum comparable to that in the hypothalamic island rats show no deficiencies in food and water intake. In fact, the operation which produces a neurally isolated hypothalamus in addition interrupts the important pathways passing through the hypothalamus between the brain stem and the limbic system, and so the animals studied here may be considered to be partial decerebrates. In this context, these experiments indicate that the extrahypothalamic pathways to and from the cerebrum participate little, if any, in the long term control of eating and drinking in the rat. This may not be true for cats, however, for a lesion similar to that described here for the rat produces a cat which will still voluntarily eat and drink [5]. There were two important differences which should be discussed between the study on
APPETITIVE BEHAVIOR AND HYPOTHALAMIC CIRCUMSECTION cats and that reported here. In the previous study the cats were usually observed for only a number of hours following lesioning, whereas the present study used chronic animals which were not observed until after at least a day following surgery. The possibility that this was a crucial difference would be strengthened if it were found that the aphagia resulting from lateral hypothalamic lesions developed slowly rather than immediately. However, in several studies [2, 9] rats have been observed as soon as 20 min following lesioning of the lateral hypothalamus and have been found to be immediately aphagic. Furthermore, two cats were observed in the previous study for several weeks following lesioning. Although neither of these cats had a perfect hypothalamic lesion, in both cases even though there was massive destruction of the hypothalamus and interruption of most of the pathways carrying hypothalamic outflows, eating continued until the time of death. A second difference is in the shape of lesions. The lesions have a slightly different form in the two studies, and this is due to species differences in shape of the hypothalamus and also is probably due to the fact that with a smaller knife, such as used in the present study, the lesion produced does not conform so exactly to the shape of the knife as it does with larger knives. However, a number of arguments are opposed to this having been a crucial difference between the two studies. The general pattern of destruction was similar in the two studies. In both cats and rats, insertion of the knife alone caused damage to the corpus callosum, septal region; and preoptic area, and in both cases eating behavior returned soon afterwards. In both cases after the knives were turned there was also some damage to the ventral and midline thalamus and to the subthalamic region. Although each animal in the present study had a slightly different lesion, each animal behaved in exactly the same manner toward food, suggesting that the exact pattern of the lesion was not too important. Although the lesions in the present study did not so closely and exactly isolate the hypothalamus as some of those in the cat did, the major pathways to and from the hypothalamus had been severed in both studies. The only hypothalamic tissue which could have escaped destruction in the study on cats was the most dorsal lateral hypothalarnic tissue at the level of the mammillary bodies. This tissue was dorsal to the fornix and medial forebrain bundle at this level, and is dorsal to the areas usually implicated in studies of eating behavior. Furthermore, this thin region had been subjected to severe trauma, was infiltrated with blood, and had its connections severed in several directions within minutes prior to the observation of eating behavior. For these reasons it seems difficult to invoke the activity of this tissue to explain the differences in eating behavior between cats and rats. Other observations on rats with hypothalamic islands which have been performed in this laboratory further argue against differences in patterns of lesions as the crucial difference between cats and rats. In one rat reeently studied, it was subsequently found that the lesion spared the posterior half of the entire lateral hypothalamus on one side. Nevertheless, this rat, studied by Mr. Paul Farel, remained aphagic for 30 days following lesioning and only then began to eat again. Another rat with a complete lesion remained aphagic until it was sacrificed 60 days after lesioning. It is difficult to explain the eating behavior in cats in terms of remaining hypothalamic tissue, for one must simultaneously explain why rats, including some of those described in Table 1, remain aphagic for long periods following lesioning in spite of similarly incomplete lesions. Although not all of the cats ate after
225
lesioning, this did not seem to correlate with shape of lesion and was probably due to the recent trauma and loss of dignity caused by the recent lesioning. The results from the cats clearly stand in contrast to those obtained from rats, none of whom ate for long periods following lesioning. Finally, there arc logical considerations which argue against using remaining lateral hypothalamic tissue to explain the eating behavior in cats without making additional assumptions, for considerably more lateral hypothalamic tissue remains intact following bilateral electrolytic lesions at just one plane of the hypothalamns than does after the operation to produce a hypothalamic island. In other words, it is difficult to explain the lack of aphagia observed in cats after circumsection of the hypothalamus solely in terms of remaining lateral hypothalamic tissue because considerably more lateral hypothalamic tissue is destroyed in the circumsection operation than is destroyed using the usual electrolytic lesion methods. The amount of lateral hypothalamic tissue which could have escaped isolation in the study on cats was perhaps 5 per cent of the total lateral hypothalamus. Because of the large differences in size and shape of brain between cats and rats, it is virtually impossible to achieve lesions in the two species which are exactly comparable. The brain of the rat is smaller than that of the cat, and the hypothalamus constitutes a larger part of its brain than does the hypothalamus of a cat. Damage to structures other than the hypothalamus must of necessity be greater when a hypothalamic island is made in the rat, and it is possible that this is in fact the crucial difference between the study on cats and that on rats. Some of the considerations raised above, on the other hand, can also be used to argue against this possibility, and more work is clearly needed on this problem. Nevertheless, the differences in behavior between cats and rats after neural isolation of the hypothalamus are indicative of some encephalization of appetitive motivation in the cat. Such a phenomenon is not unreasonable as learned factors come to play a greater role in the feeding behavior of higher species. A previous study which compared the effects of lateral hypothalamic lesions in monkeys and cats [1] also found evidence for encephalization of appetitive motivational function. The observation that cats in which the hypothalamus is the highest remaining structure intact do not show eating behavior [6] indicates that hypothalamic influences alone are not sufficient for appetitive behavior in the cat. A second implication of the present results also deserves discussion. Cutting the major pathways to and from the hypothalamus results in a rat which neither spontaneously consumes nor actively rejects food, whereas a rat with lateral hypothalamic lesions actively rejects food placed in the mouth. If a rat after removal of all hypothalamic influences behaves as though he were not motivated to eat, a rat after destruction of only the lateral hypothalamus behaves as though he were motivated not to eat. Aphagia seems to be only a partial description of an animal after lateral hypothalamic lesions. Not only are they aphagic, as are decerebrates, but they in addition actively reject food placed in their mouths, and this is something a decerebrate does not do. This active rejection of food after lateral hypothalamic lesions has been reported for rats [11], cats [1], and most monkeys [1] after lateral hypothalamic damage. The active rejection of food after discrete lesions of the lateral hypothalamus seems to be a result not so much of a reduction in the lateral hypothalamic "hunger" signals p e r se, but rather is due to the now unbalanced inhibitory signals emanating from the medial "satiety" center. According to this notion, these inhibitory
226
ELLISON
signals apparently have a motivational effect all their own and do not act solely upon the lateral hypothalamus. The inhibitory effects of unbalanced satiety signals can be so pronounced as to allow cats with lesions of only the lateral hypothalamus to actively reject food placed in their mouths but to actively eat with all hypothalamic influences removed. A recent study of the visual system [10] has verified that such long term inhibitory effects can occur in lesion studies. Further attempts have been made in this laboratory to study animals with electrolytic lesions of both the lateral and ventromedial hypothalamus in order to confirm this notion, but such animals have been invariably comatose following lesioning and have never recovered to the extent where meaningful behavioral observations could be made before recovery of function took place.
The finding that a lateral animal is not the same as a hypothalarnic animal has implications for general notions of hypothalamic function. It indicates that inflated estimates of the extent of hypothalamic control can be obtained from discrete lesion studies, for an animal after partial hypothalamic destruction can show behavior toward food which differs more from normal behavior than that observed in an animal with total hypothalamic destruction. These results also suggest that the phenomenon of recovery of function following partial lesions of the lateral hypothalamus alone could be understood not only in terms of the recovery of lateral function, but also alternatively in terms of a gradual functional diminution of influence from an underbalanced medial hypothalamus.
REFERENCES 1. Anand, B. K., S. Dua and K. Schoenberg. Hypothalarnic control of food intake in cats and monkeys. J. Physiol., London, 127: 143-152, 1955. 2. Baille, P. and S. D. Morrison. The nature of the suppression of food intake by lateral hypothalamic lesions in rats. J. PhysioL, London. 165: 227-245, 1963. 3. Bard, P. and M. B. Maeht. The behavior of chronically decerebrate cats. In: The Neurological Basis of Behavior, edited by M. O'Connor and G. E. W. Wolstenholme. London: J. and A. Churchill, pp. 55-75, 1958. 4. deGroot, J. The rat forebraln in stereotaxic coordinates. Verh. Kon. Ned. Akad. Wet., A. Natuurkunde, 52: 1--40, 1959. 5. Ellison, G. and J. P. Flynn. Organized aggressive behavior in cats after neural isolation of the hypothalamus. Arch. ital. Biol. (in press). 6. Emmers, R., R. Chun and G. Wang. Behavior and reflexes of chronic thalamic eats. Arch. ital. Biol. 103: 178-193, 1965. 7. Halasz, B. and R. A. Gorski. Gonadotrophic hormone secretion in female rats after partial or total interruption of neural afferents to the medial basal hypothalamus. Endocrinology 80: 608--622, 1967.
8. Halasz, B. and L. Pupp. Hormone secretion of the anterior pituitary gland after physical interruption of all nervous pathways to the hypophysiotrophic area. Endocrinology 77: 553-562, 1965. 9. Rogers, W. L., A. N. Epstein and P. Teitelbanm. Lateral hypothalamic aphagia: motor failure or motivational deficit? Am. J. PhysioL 208: 334-342, 1965. 10. Sprague, J. M. Interaction of cortex and superior colloculus in mediation of visually guided behavior in the cat. Science 153: 1544-1547, 1966. 11. Teitelbaum, P. and A. N. Epstein. The lateral hypothalamic syndrome: recovery of feeding and drinking after lateral hypothalamic lesions. Psychol. Rev. 69: 74-90, 1962. 12. Woods, J. W. Behavior of chronic decerebrate rats. J. Neurophysiol. 27: 635-644, 1964. 13. Woods, J. W., P. Bard and R. Bleier. Functional capacity of the deafferented hypothalamus: water balance and responses to osmotic stimuli in the decerebrate cat and rat. J. Neurophysiol. 29: 751-767, 1966.
Appetitive Behavior in Rats after Circumsection of the Hypothalamus' GAYLORD
D. E L L I S O N
Department of Psychology, University of California, Los Angeles (Received 2 June 1967) ELLISON,G.D. Appetitivebehaviorin rats after circumsectionof the hypothalamus. PHYSIOL.BEHAV.3 (2) 221--226, 1968.-Hypothalamic islands were made in rats by means of a knife which was inserted down into the brain and then rotated so as to sever the neural connections of the hypothalamus with the rest of the brain while leaving intact its connections with the pituitary gland. Rats are aphagic and adipsic after the major pathways from the hypothalamus are cut, but their syndrome is similar to that seen in decerebrate rats rather than like that in rats with lateral hypothalamic lesions. These results stand in contrast with those obtained from cats, who can show eating behavior immediately after similar neural isolation of the hypothalamus. Hypothalamus
Adipsia
Aphagia
Rats
had been malleted flat, honed sharp, and bent into shape, and was housed in a shaft made of 20 gauge hypodermic tubing so that it could be rotated while in the brain, cutting the sides and top of a cylinder 7 mm in dia. and 1.5 mm deep.
ALTHOUGH the hypothalamus is generally considered to be essential for the occurrence of spontaneous motivated behavior in an integrated form, there have been few studies of the behavioral capabilities of animals lacking an entire hypothalamus but with the rest of the brain intact. This is undoubtedly due to the technical difficulties involved in making extensive lesions of this area. It has recently proved possible to study animals in which an island of hypothalamic tissue has been created by means of a knife initially inserted down through the brain along the midline and then rotated so as to sever the neural connections of the hypothalamus with the rest of the brain while leaving intact its connections with the pituitary body. In a recent study using this revolving knife technique [5], it was found that cats even though deprived of neural influences from the hypothalamus showed a wide range of aggressive and appetitive behaviors, and in particular voluntarily ingested food within minutes after lesioning. This result was unexpected since it is widely believed that voluntary eating and more generally hunger depend upon the integrity of a lateral hypothalamic "hunger" center which is normally held in check by a medial hypothalamic "satiety" center. Because many of the studies which have given rise to this conception have used rats as subjects, further experiments were undertaken to study feeding behavior in the rat following neural isolation of the hypothalamus. Previous studies using the revolving knife technique on rats have been confined to the use of a small knife designed to deafferent the pituitary and medial hypothalamus alone [7, 8].
/ ~/
,20 GAUGE TUBING
,,-7-i<--
35mm
FIG. 1. The knife used to produce the lesions, as described in the text. The blades, one of which faces the viewer, were sharpened under a microscope until they would break the skin when stroked across the experimenter's finger.
METHOD
The lesions were produced by means of the knife shown in Fig. 1. It was made from stainless steel of 0.020 in. dia. which
XThis research supported in part by NIH grant MH 12,841. I thank F. Helmholz, D. Parker, and H. Reznick for assistance in conduction of these experiments, R. Gorski for advice in construction of the knife, and D. Novin for histological assistance. 221
222
ELLISON
The rats were placed in a stereotaxic instrument like that described by deGroot [4] in order to make the lesion. A bone flap about 3 × 5 mm was removed along the midline with care taken not to rupture the superior saggital sinus, and the dura was cut immediately adjacent to the sinus. The knife, the shaft of which was fixed at 70 ° to horizontal in the saggital plane (the top of the shaft being most posterior), was then lowered into the brain immediately adjacent to the sinus. When the blade of the knife had passed the level of the sinus, the knife was moved medially so as to be exactly along the midline and then ventrally (along the angle of the shaft) until the anterior tip of the knife rested at AP + 9.9, H-1.3, and L 0. The knife was then rotated several times in both directions, returned to its original position with the blade facing anteriorly, and retracted in the same manner it had been lowered. In the preceding description the final position of the knife is given in deGroot coordinates. In actual practice the final position of the knife was arrived at by placing the hub of the knife at stereotaxic zero with the shaft at the 70 ° angle to horizontal and then calculating coordinates so that the knife was moved anteriorly 7.75 mm and dorsally 4.75 mm along the angle of the shaft. The knife (facing anteriorly) is shown in position using these latter measurements in Fig. 2 with the rat oriented in the stereotaxic instrument.
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29c of Krieg) had been damaged unilaterally when the knife was inserted. The anterior half of the corpus callosum had been sectioned by the knife as it was lowered, as was the hippocampal commissure. There was considerable damage to the medial and lateral septal nuclei and some damage to the preoptic area and to the most anterior parts of the paraventricular and reuniens nuclei of the thalamus. Eating behavior returned in such control animals on the first or second day following surgery and appeared normal thereafter. In 7 animals in which the knife was rotated, the knife cuts typically started anterior to the optic chiasm, and at the level of the anterior commissure extended out to include all of the medial and much of the lateral preoptic area but usually failed to extend completely to the base of the brain. At the level of the ventromedial nuclei of the hypothalamus, the island included all of the lateral hypothalamus. The lesion remained as far lateral as the internal capsule more posteriorly and extended dorsally to include part of the ventral thalamus. The island ended just posterior to the mammillary bodies. Figure 3 presents four sections from an animal which survived for 29 days following surgery. In this animal the knife cuts extend ventrally to the base of the brain in the posterior hypothalamus but stop short more anteriorly, a pattern which varied from animal to animal. Because the main efferents from the hypothalamus generally course in either a dorsal or a posterior direction, the main outflows from the hypothalamus have been eliminated in this animal. Figure 4 shows an enlarged segment from one of the sections in Fig. 3 so that the lesion can be seen more clearly. Sections from five other animals are presented in Fig. 5. In assessing the extent to which the lesions have effectively created an animal in which the neural influences from the hypothalamus have been eliminated, attention should be directed toward the degree of interruption of fiber systems to and from the hypothalamus rather than the extent of destruction p e r se. I n
TABLE EXTENT OF DAMAGE
llO° ~ , ~ n [ e r a u r a i
line
1
TO THE MAJOR HYPOTHALAMIC PATHWAYS IN EACH OF THE ANIMALS.
~"f 7.5 mm -~
Animal No.
FIG. 2. The knife shown in position and facing anteriorly. The diagram represents a rat held in place in the stereotaxic instrument.
HI2 H13 H16 H19 H20 H22 H25 Dorsal longitudinal fase. t t tt tt tt ¢t tt tt Columns of fomix tt tt tt tt tt tt tt Habenulopeduncular
Postoperatively the animals were housed in an incubator. The temperature of the incubator was regulated so as to maintain the rectal temperature of the rats at about 34C °. Each animal had constant access to a liquid diet, water, and lab chow pellets, the edges of which had been ground smooth so that it was possible to detect any attempts to eat them. The liquid diet, which was similar to that used in previous studies, was a mixture of 270 ml of Sego or Nutrament brand liquid diet (chocolate flavor), 30 g sucrose, 15ml. Kaopectate, and 0.4 cc formaldehyde as a preservative.
Inferior thalamic peduncle Mammillary peduncle Mamrnillothalamictract Mammillotegmental tract Medial forebrain bundle: rostrally caudally Periventricular thal-hypothal, Stria medullaris Stria terrninalis Ventral amyg-subeortical
tract
tt
tt
tt
tt
tt
tt
tt
tt
tt
tt
tt
tt
tt
tt
tt
¢ tt
tt
tt tt
tt tt
tt tt
* tt
tt
tt
tt
tt
tt
tt
tt
-
t
-
tt
tt
t tt
tt tt
t tt
tt
tt tt
tt
-
-
tt tt tt
tt tt tt
tt tt tt
tt tt tt
tt
tt
-
tt
tt
tt
tt tt tt
-
-
-
*
RESULTS
In 4 control animals in which the knife was lowered into position and withdrawn without being rotated, subsequent histology revealed that the midline cortex (parts of areas 4 and
¢tindicates bilateral destruction; "]'indicates unilateral destruction; indicates not destroyed; *indicates that it was not possible to determine amolmt of destruction because of an error in histology.
r
II
FIG. 3. Photographs of 4 sections from animal H22. Section " a " is at the level of the optic chiasm, sect/on "'b" at the level of the ventromedial nuclei of the hypothalamus, section "c" at the posterior tip of the ventromedial nuclei, and section " d " at the level of the mammillary bodies. Paraffin sections with cresyl violet stain.
( 1 o ¢ i ~ pa~ e
222)
FIG. 4. An enlarged segment of section "c" in Fig. 3. The cut can be seen extending bilaterally to the base of the brain.
FIG. 5. Sections showing the lesion in 5 other animals. From the top down, the sections are from animal H25, H20, HI3, HI2, and HI6. Paraffin sections with cresyl violet stain.
APPETITIVE BEHAVIOR AND HYPOTHALAMIC CIRCUMSECTION Table 1 the extent of damage to the major afferent and efferent pathways of the hypothalamus is listed for each animal. In order to better present the pattern of destruction of structures other than the hypothalamus, drawings corresponding to sections from the deGroot atlas were made and the lesions of three rats projected upon these figures. The results are presented as Fig. 6. As was found previously using the revolving knife technique on cats, chronic animals prepared in this manner frequently are found to have expanded ventricles, and the wound caused by the knives also frequently appears to have been expanded. This is why the size of the lesions in Fig. 6 often do not appear to correspond exactly to those in Figs. 3 and 5. These six animals were observed postoperatively for periods ranging from 20 to 33 days; one other animal was
223
hind paw of a lesioned rat was pinched. Because the lesions were near, and sometimes encroached upon, the medial lemniseus, further experiments were performed to determine if taste impulses could still be recorded at the cortex after lesioning. It was found that the cortical evoked potential elicited by stimulation of the ninth cranial nerve after sectioning of the pharyngeal branch was not destroyed by the hypothalamic island lesion. Auditory startle reflexes were present in these animals but it was not determined whether or not these animals were blind, although a number of attempts were made to do so. The behavior of these rats was consistent from animal to animal. By the third day postoperatively they had recovered sufficiently so that a number of behaviors could be observed. They were not comatose, but rather could usually be observed
FIG. 6. Reconstructionsofthelesionssuperimposed ondrawingsrepresenting sections from deGroot. The column on the left presents the lesion in H22, the column in the center is from animal H20, and the column on the right represents the lesion in animal HI9. The top row of drawings are from a section through the optic chiasm, the second row through the ventromedial nuclei of the hypothalamus, the third row through the mammiUary bodies, and the last row just posterior to the rnammillary bodies. The lesion in each case is represented by the solid dark area.
sacrificed 9 days after lesioning. Immediately upon lesioning the body temperature of these animals fell drastically, and so they were housed in an incubator which was thermostatically regulated. As the animals recovered from the lesion it was possible to gradually lower the temperature of the incubator, but no animal ever reached the point where it could be left at room temperature. Because the operation to isolate the hypothalamus also produced some thalamic damage, it was necessary to demonstrate that these rats were not functional decerebrates. It was found that tactile placing reactions, which are absent in decerebrate rats [12], were present bilaterally in all rats. Olfactory reflexes were present to pyridine, although trigeminal involvement could not be ruled out. A synchronizer E E G recorded from the cortex desynchronized rapidly when the
sitting in their cages grooming. When picked up roughly or pinched on the flank, vigorous escape efforts were observed, including squealing, struggling, and attempts to bite the experimenter's hand. When placed on the floor after such escape attempts the rat would run from the experimenter. Polyuria was not observed in any of these animals, indicating that the hypothalamic island was functioning [3, 13]. A Richter drinking tube containing liquid diet was constantly available to each of these animals. The high ambient temperature of the incubator increased evaporation loss, so each animal's daily diet intake was measured by comparing the loss from the animal's tube with that from a control tube. Using this measure, none of the animals postoperatively drank any liquid diet while in the home cage. The same was true of water intake, which was also compared with a control tube.
224 The laboratory chow pellets never showed any evidence of gnawing. The aphagia and adipsia were in contrast to the behavior of" these rats when hand-fed. When an eyedropper filled with liquid diet was brought to the lips of a lesioned rat, it would frequently open its mouth, turn its head toward the dropper, and grasp the dropper with its teeth. Care was taken to insure that the dropper was not inserted deep into the rat's mouth. Rather, the tip was normally inserted only 2-3 mm into the mouth. Diet then injected into the rat's mouth was immediately swallowed while the rat held the dropper with its front paws. Daily feedings of 15 cc's of the liquid diet were routinely given in this manner. In order to insure that this fluid was really being consumed, the rats were weighed both before and after daily feedings. After the first 3 cc's of diet the average weight gain of 4 rats was 2.8 g, and after 15 cc's the average weight gain was 13.1 g. These data are for the last 4 rats, from whom the most data were collected, but comparable data were collected from the other rats as well. A similar acceptance of food was observed when the rats were placed on a solid surface and bits of milk chocolate or lab chow were placed against their lips. A lesioned rat would grasp the food with a paw, gnaw on the food, and consume it. Similar behavior was also observed, however, when inedible objects were brought to the rat's lips. A pencil would be repeatedly grasped with the paw and gnawed, although unpleasant tasting substances were rejected. These rats, then, showed feeding reactions identical to those reported for decerebrate rats [12]. It should be noted that these feeding reactions were not merely aggressive attempts on the part of the rats to bite at anything placed in their mouths. The pattern of feeding reactions reported could be observed only during times when the rats were relatively calm and consisted principally of repetitive lapping movements with frequent swallowing and little biting. The experimenter's finger could be safely inserted into their mouths during feeding sessions; this resulted merely in a gnawing on the finger without the drawing of blood. Animals can be forced to swallow food by manipulation of aggressive reactions, but the pattern of swallowing in such a case is entirely different. It occurs during vigorous struggling to escape. Such swallowing also occurs mainly when the mouth is very full and food is on the back of the tongue, and is invariably accompanied by biting at the utensil used to place the food in the mouth. When struggling occurred in the rats reported here (this occurred more frequently just after lesioning, as these animals had not been pretamed), the rat was placed on the floor and calmed rather than having diet forcibly injected into the mouth. Some liquid diet was inevitably spilled while feeding these rats with the eyedropper. This diet dried on their fur, and most of the spontaneous activity observed in these rats consisted of grooming. Grooming attempts also accounted for most of the interruptions in hand feeding. Aphagia and adipsia also occur after smaller electrolytic lesions of the lateral hypothalamus alone, but previous descriptions of such rats have indicated that they will not readily accept food placed directly into the mouth [9, 11]. In order to better compare feeding reactions of lateral hypothalamic rats with hypothalamic island rats, bilateral electrolytic lesions of the lateral hypothalamus were attempted in 12 rats. In 5 of these rats long term aphagia and adipsia were successfully obtained. These 5 rats, which were apparently healthy after lesioning but subsequently died from starvation even though dry food, liquid diet, and water were available,
ELLISON consistently rejected the liquid diet when placed in the mouth. These animals would typically push the eyedropper away with the paws when it was brought to the mouth and viciously bite the dropper when it was forced into the mouth. The head was turned from side to side, apparently in attempts to escape from the dropper. When diet was forcibly injected into the mouth, some would initially be swallowed (this amount varied from 0.3-1.5 cc in different rats) but then the rat would stop swallowing and allow any further diet to run out of the mouth. The average weight gain after 3 cc's were injected into their mouth was 0.9 cc, some of which was spilled diet on the rat's fur. This value was significantly less (p <0.05) than the comparable weight gain for rats with a hypothalamic island. A number of rating scales were devised in an attempt to further quantify the differences in food acceptance between the hypothalamic island and the lateral hypothalamic lesion groups. None of these were consistently successful, chiefly because of the wide variety of behaviors used by different animals with lateral hypothalamic lesions to avoid the dropper. A double-blind control experiment was also impracticable because of other obvious differences in behavior between the two groups. However, all of the weight gain after feeding data reported here were obtained by two independent observers, both of whom were technicians and neither of whom understood the nature of the experiment. Each of these observers fed both hypothalamic island and lateral hypothalamic lesion animals. Each used terms similar to "acceptance" and "rejection" to describe the feeding behavior of the two respective groups. The remainder of the animals with lateral lesions can be divided into two groups. Five animals accepted diet from the eyedropper after lesioning, and voluntary feeding returned in each of these animals from two to six days after lesioning. Two other animals were comatose just after lesioning, and these animals did not reject liquid diet placed in their mouth while they were comatose. One of these animals died a week after lesioning; the second recovered spontaneous activity and began rejecting food until it died on the 15th postoperative day. DISCUSSION
Rats after circumsection of the hypothalamus are aphagic and adipsic, behaving toward food and water exactly as do deeerebrate rats. In some of these rats almost all of the tracts to and from the hypothalamus have been sectioned (cf. Table 1), and their behavior therefore is probably representative of rats after the elimination of neural influences from the hypothalamus. Other rats subjected to control lesions which cause damage to the midline thalamus and septum comparable to that in the hypothalamic island rats show no deficiencies in food and water intake. In fact, the operation which produces a neurally isolated hypothalamus in addition interrupts the important pathways passing through the hypothalamus between the brain stem and the limbic system, and so the animals studied here may be considered to be partial decerebrates. In this context, these experiments indicate that the extrahypothalamic pathways to and from the cerebrum participate little, if any, in the long term control of eating and drinking in the rat. This may not be true for cats, however, for a lesion similar to that described here for the rat produces a cat which will still voluntarily eat and drink [5]. There were two important differences which should be discussed between the study on
APPETITIVE BEHAVIOR AND HYPOTHALAMIC CIRCUMSECTION cats and that reported here. In the previous study the cats were usually observed for only a number of hours following lesioning, whereas the present study used chronic animals which were not observed until after at least a day following surgery. The possibility that this was a crucial difference would be strengthened if it were found that the aphagia resulting from lateral hypothalamic lesions developed slowly rather than immediately. However, in several studies [2, 9] rats have been observed as soon as 20 min following lesioning of the lateral hypothalamus and have been found to be immediately aphagic. Furthermore, two cats were observed in the previous study for several weeks following lesioning. Although neither of these cats had a perfect hypothalamic lesion, in both cases even though there was massive destruction of the hypothalamus and interruption of most of the pathways carrying hypothalamic outflows, eating continued until the time of death. A second difference is in the shape of lesions. The lesions have a slightly different form in the two studies, and this is due to species differences in shape of the hypothalamus and also is probably due to the fact that with a smaller knife, such as used in the present study, the lesion produced does not conform so exactly to the shape of the knife as it does with larger knives. However, a number of arguments are opposed to this having been a crucial difference between the two studies. The general pattern of destruction was similar in the two studies. In both cats and rats, insertion of the knife alone caused damage to the corpus callosum, septal region; and preoptic area, and in both cases eating behavior returned soon afterwards. In both cases after the knives were turned there was also some damage to the ventral and midline thalamus and to the subthalamic region. Although each animal in the present study had a slightly different lesion, each animal behaved in exactly the same manner toward food, suggesting that the exact pattern of the lesion was not too important. Although the lesions in the present study did not so closely and exactly isolate the hypothalamus as some of those in the cat did, the major pathways to and from the hypothalamus had been severed in both studies. The only hypothalamic tissue which could have escaped destruction in the study on cats was the most dorsal lateral hypothalarnic tissue at the level of the mammillary bodies. This tissue was dorsal to the fornix and medial forebrain bundle at this level, and is dorsal to the areas usually implicated in studies of eating behavior. Furthermore, this thin region had been subjected to severe trauma, was infiltrated with blood, and had its connections severed in several directions within minutes prior to the observation of eating behavior. For these reasons it seems difficult to invoke the activity of this tissue to explain the differences in eating behavior between cats and rats. Other observations on rats with hypothalamic islands which have been performed in this laboratory further argue against differences in patterns of lesions as the crucial difference between cats and rats. In one rat reeently studied, it was subsequently found that the lesion spared the posterior half of the entire lateral hypothalamus on one side. Nevertheless, this rat, studied by Mr. Paul Farel, remained aphagic for 30 days following lesioning and only then began to eat again. Another rat with a complete lesion remained aphagic until it was sacrificed 60 days after lesioning. It is difficult to explain the eating behavior in cats in terms of remaining hypothalamic tissue, for one must simultaneously explain why rats, including some of those described in Table 1, remain aphagic for long periods following lesioning in spite of similarly incomplete lesions. Although not all of the cats ate after
225
lesioning, this did not seem to correlate with shape of lesion and was probably due to the recent trauma and loss of dignity caused by the recent lesioning. The results from the cats clearly stand in contrast to those obtained from rats, none of whom ate for long periods following lesioning. Finally, there arc logical considerations which argue against using remaining lateral hypothalamic tissue to explain the eating behavior in cats without making additional assumptions, for considerably more lateral hypothalamic tissue remains intact following bilateral electrolytic lesions at just one plane of the hypothalamns than does after the operation to produce a hypothalamic island. In other words, it is difficult to explain the lack of aphagia observed in cats after circumsection of the hypothalamus solely in terms of remaining lateral hypothalamic tissue because considerably more lateral hypothalamic tissue is destroyed in the circumsection operation than is destroyed using the usual electrolytic lesion methods. The amount of lateral hypothalamic tissue which could have escaped isolation in the study on cats was perhaps 5 per cent of the total lateral hypothalamus. Because of the large differences in size and shape of brain between cats and rats, it is virtually impossible to achieve lesions in the two species which are exactly comparable. The brain of the rat is smaller than that of the cat, and the hypothalamus constitutes a larger part of its brain than does the hypothalamus of a cat. Damage to structures other than the hypothalamus must of necessity be greater when a hypothalamic island is made in the rat, and it is possible that this is in fact the crucial difference between the study on cats and that on rats. Some of the considerations raised above, on the other hand, can also be used to argue against this possibility, and more work is clearly needed on this problem. Nevertheless, the differences in behavior between cats and rats after neural isolation of the hypothalamus are indicative of some encephalization of appetitive motivation in the cat. Such a phenomenon is not unreasonable as learned factors come to play a greater role in the feeding behavior of higher species. A previous study which compared the effects of lateral hypothalamic lesions in monkeys and cats [1] also found evidence for encephalization of appetitive motivational function. The observation that cats in which the hypothalamus is the highest remaining structure intact do not show eating behavior [6] indicates that hypothalamic influences alone are not sufficient for appetitive behavior in the cat. A second implication of the present results also deserves discussion. Cutting the major pathways to and from the hypothalamus results in a rat which neither spontaneously consumes nor actively rejects food, whereas a rat with lateral hypothalamic lesions actively rejects food placed in the mouth. If a rat after removal of all hypothalamic influences behaves as though he were not motivated to eat, a rat after destruction of only the lateral hypothalamus behaves as though he were motivated not to eat. Aphagia seems to be only a partial description of an animal after lateral hypothalamic lesions. Not only are they aphagic, as are decerebrates, but they in addition actively reject food placed in their mouths, and this is something a decerebrate does not do. This active rejection of food after lateral hypothalamic lesions has been reported for rats [11], cats [1], and most monkeys [1] after lateral hypothalamic damage. The active rejection of food after discrete lesions of the lateral hypothalamus seems to be a result not so much of a reduction in the lateral hypothalamic "hunger" signals p e r se, but rather is due to the now unbalanced inhibitory signals emanating from the medial "satiety" center. According to this notion, these inhibitory
226
ELLISON
signals apparently have a motivational effect all their own and do not act solely upon the lateral hypothalamus. The inhibitory effects of unbalanced satiety signals can be so pronounced as to allow cats with lesions of only the lateral hypothalamus to actively reject food placed in their mouths but to actively eat with all hypothalamic influences removed. A recent study of the visual system [10] has verified that such long term inhibitory effects can occur in lesion studies. Further attempts have been made in this laboratory to study animals with electrolytic lesions of both the lateral and ventromedial hypothalamus in order to confirm this notion, but such animals have been invariably comatose following lesioning and have never recovered to the extent where meaningful behavioral observations could be made before recovery of function took place.
The finding that a lateral animal is not the same as a hypothalarnic animal has implications for general notions of hypothalamic function. It indicates that inflated estimates of the extent of hypothalamic control can be obtained from discrete lesion studies, for an animal after partial hypothalamic destruction can show behavior toward food which differs more from normal behavior than that observed in an animal with total hypothalamic destruction. These results also suggest that the phenomenon of recovery of function following partial lesions of the lateral hypothalamus alone could be understood not only in terms of the recovery of lateral function, but also alternatively in terms of a gradual functional diminution of influence from an underbalanced medial hypothalamus.
REFERENCES 1. Anand, B. K., S. Dua and K. Schoenberg. Hypothalarnic control of food intake in cats and monkeys. J. Physiol., London, 127: 143-152, 1955. 2. Baille, P. and S. D. Morrison. The nature of the suppression of food intake by lateral hypothalamic lesions in rats. J. PhysioL, London. 165: 227-245, 1963. 3. Bard, P. and M. B. Maeht. The behavior of chronically decerebrate cats. In: The Neurological Basis of Behavior, edited by M. O'Connor and G. E. W. Wolstenholme. London: J. and A. Churchill, pp. 55-75, 1958. 4. deGroot, J. The rat forebraln in stereotaxic coordinates. Verh. Kon. Ned. Akad. Wet., A. Natuurkunde, 52: 1--40, 1959. 5. Ellison, G. and J. P. Flynn. Organized aggressive behavior in cats after neural isolation of the hypothalamus. Arch. ital. Biol. (in press). 6. Emmers, R., R. Chun and G. Wang. Behavior and reflexes of chronic thalamic eats. Arch. ital. Biol. 103: 178-193, 1965. 7. Halasz, B. and R. A. Gorski. Gonadotrophic hormone secretion in female rats after partial or total interruption of neural afferents to the medial basal hypothalamus. Endocrinology 80: 608--622, 1967.
8. Halasz, B. and L. Pupp. Hormone secretion of the anterior pituitary gland after physical interruption of all nervous pathways to the hypophysiotrophic area. Endocrinology 77: 553-562, 1965. 9. Rogers, W. L., A. N. Epstein and P. Teitelbanm. Lateral hypothalamic aphagia: motor failure or motivational deficit? Am. J. PhysioL 208: 334-342, 1965. 10. Sprague, J. M. Interaction of cortex and superior colloculus in mediation of visually guided behavior in the cat. Science 153: 1544-1547, 1966. 11. Teitelbaum, P. and A. N. Epstein. The lateral hypothalamic syndrome: recovery of feeding and drinking after lateral hypothalamic lesions. Psychol. Rev. 69: 74-90, 1962. 12. Woods, J. W. Behavior of chronic decerebrate rats. J. Neurophysiol. 27: 635-644, 1964. 13. Woods, J. W., P. Bard and R. Bleier. Functional capacity of the deafferented hypothalamus: water balance and responses to osmotic stimuli in the decerebrate cat and rat. J. Neurophysiol. 29: 751-767, 1966.