Physiology & Behavior, Vol. 23, pp. 439--443.PergamonPress and BrainResearch Publ., 1979. Printedin the U.S.A.
Mouse Killing and Hyperreactivity Following Lesions of the Medial Hypothalamus, the Lateral Septum, the Bed Nucleus of the Stria Terminalis, or the Region Ventral to the Anterior Septum D. J. A L B E R T a A N D K. N. B R A Y L E Y P s y c h o l o g y D e p a r t m e n t , U n i v e r s i t y o f British C o l u m b i a Vancouver, B.C., Canada, V6T 1W5 R e c e i v e d 26 J a n u a r y 1979 ALBERT, D. J. AND K. N. BRAYLEY. Mouse killing and hyperreactivity following lesions of the medial hypothalamus, the lateral septum, the bed nucleus of the stria terminalis, or the region ventral to the anterior septum. PHYSIOL. BEHAV. 23(3)439--443, 1979.--Electrolytic lesions in the medial hypothalamus, the lateral septum, or the region ventral to the anterior septum induced home cage mouse killing in 85 to 100% of rats when tested 2 days postoperatively and in 50 to 70% when tested at 21 days. When tested in a novel and larger test chamber, 100% of the rats with medial hypothalamic lesions killed mice at 2 days postoperatively but only 30% killed at 21 days postoperatively. Ten to thirty percent of animals with lesions of the lateral septum or of the region ventral to the anterior septum killed at any time in the novel environment. Lesions of the stria terminalis produced a slight increase in mouse killing in both the home cage and the novel environment. A high level of reactivity was produced by lesions of the medial hypothalamus, the lateral septum or the region ventral to the anterior septum but only that caused by the medial hypothalamic lesions was sustained over the 21 day test period. These results support previous evidence that the lateral septum, the region ventral to the anterior septum, and the medial hypothalamus are each important areas modulating mouse killing. Aggression
Lateral septum
Medial hypothalamus
MOUSE killing is increased by electrolytic lesions in the medial hypothalamus, the septum, and the stria terminalis. It occurs in 30 to 50% of rats with lesions of the medial hypothalamus [5, 6, 9]. In contrast, lesions of the medial and lateral septum have induced mouse killing in 100% of rats in one experiment but in only 12% in another [6,7]. Stria terminalis lesions appear to slightly augment mouse killing particularly when the rats are food deprived [14], yet lesions of the bed nucleus of the stria terminalis reportedly are without effect [8]. These studies suggest that the septum and the medial hypothalamus may not be equally involved in the modulation of mouse killing and that the stria terminalis may be involved in yet a quite different way. However, the validity of these conclusions is difficult to evaluate because the experiments have been conducted differently and, in addition, the size of the lesions in each area have been quite variable. Recent
Mouse killing
Reactix,ity
Stria terminalis
work using temporary chemical lesions purports to have localized the regions in the septal area [4] and the medial hypothalamus [3] which are involved in modulating mouse killing. In addition, an area ventral to the anterior septum has been found to modulate mouse killing [4]. Accordingly, it now seems possible to compare the effect of electrolytic lesions in these various areas in a single study using a common procedure and where the tissue thought to be involved in modulating mouse killing in each area is consistently removed. The present experiments compared the effect on mouse killing of lesions at four sites: the medial hypothalamus, the lateral septum, the region ventral to the anterior septum, and the bed nucleus of the stria terminalis. Mouse killing was examined both in the home cage and in a novel test chamber at various intervals following the lesions. The effect of each lesion on reactivity to the experimenter was also examined.
~Supported by a grant from the National Research Council of Canada. Reprint requests to: D. J. Albert, Psychology Department, University of British Columbia, Vancouver, B.C., Canada V6T IW5.
C o p y r i g h t © 1979 B r a i n R e s e a r c h P u b l i c a t i o n s Inc.--0031-9384/79/090439-05501.00/0
440
ALBERT AND BRAYI.EY METHOD
Animals The animals were 41 male hooded rats weighing 350-450 g (Canadian Breeding Farms and Laboratories, Quebec, Canada). They were housed in group cages prior to surgery and in individual cages thereafter.
ttistology Following behavioral testing the brains of all animals were removed and placed in formol-saline. They were later sectioned on a cryostat and stained with cresyl violet. RESU LTS
Mouse Killing Surgical Procedure The animals were divided into five groups according to the intended location of their lesions. Bilateral DC lesions were made using a stainless steel electrode (0.5 mm dia.) connected to the anode and the cathode attached to the tall. The hypothalamic coordinates were: anterior to bregma 0.0 ram, lateral 0.7 mm, ventral to the cortical surface 9.0 mm (DeGroot c.oordinates; 2.0 mA, 30 sec). Bilateral lesions ventral to the anterior septum (2.0 mA, 25 sec) were made at 2.9 mm anterior to bregma, 1.2 mm lateral to the midline, and 6.8 mm ventral to the cortical surface. Bilateral lesions of the bed nucleus of the stria terminalis (2.0 mA, 20 sec) were located 1.1 mm anterior to bregma, 1.3 mm lateral, and 5.7 mm ventral to the cortical surface. Bilateral lesions were made at two sites in the lateral septum of each animal. The coordinates for the first were: 1.6 mm anterior to bregrna, 0.7 mm lateral, and 4.5 mm ventral to the cortical surface. The second lesion was made at 2.3 mm anterior to bregma, 0.7 mm lateral, and 4.5 mm ventral to the cortical surface (both lesions were made with 2.0 mA, 25 sec). Animals in the control group had electrodes lowered at one of these lesion sites but no current was passed.
Behavioral Testing All animals were tested for muricide and reactivity on postoperative Days 2, 7, 14, and 21. Muricide was examined by putting a white albino mouse (about 35 g) into the rat's living cage (17x24x 17 cm high) for 5 min and recording the latency to kill. Reactivity was measured at 1 hr following the muricide test in a 6 0 x 6 0 x 6 0 cm high box with gray walls, an open top, and wood shavings on the floor. Testing was done in the animal's colony area. The animal was dumped from its living cage onto the floor of the test chamber and then allowed to explore for 5 min before the reactivity test began. The reactivity test has been described in detail previously [2]. Briefly, the animal is given a score of 0 to 3 (0 indicating little or no response, and 3 indicating a highly aggressive or reactive response) for its response to each of 6 stimuli (presentation of a pencil, a tap on the back, presentation of a gloved hand, a poke in the side, grasping by the tail, and grasping by the abdomen) and on the amount of vocalization and amount of biting observed during testing [2, 3, 4]. The maximum score possible is 24. Immediately following the reactivity test, each rat that had killed a mouse in its home cage was given a 5 min test for muricide in the less familiar surroundings of the reactivity test chamber. Only animals that had killed in the home cage were tested for mouse killing in the chamber because preliminary experiments showed that mouse killing in the novel test chamber is very unlikely to occur in animals that have not killed in the home cage. Latency to kill was again recorded.
Lesions of the medial hypothalamus (N =7), the region ventral to the anterior septum (N=8) or the lateral septum (N=8) each produced a high percentage of killers in the home cage muricide test (Fig. 1). The proportion of killers in each group was reliably greater than in the control group at each test interval (Fisher's exact probability tests, all p ' s < 0 . 0 5 ; all p-values are two-tailed unless indicated). The latency to kill for the animals which killed was similar in each of these groups (10 to 20 sec). Stria terminalis lesions (N =5) produced a greater frequency of muricide than the sham lesions only on the first day (Day 2; p
Mouse Killing and Hyperreactivity Following Lesions of the Medial Hypothalamus, the Lateral Septum, the Bed Nucleus of the Stria Terminalis, or the Region Ventral to the Anterior Septum D. J. A L B E R T a A N D K. N. B R A Y L E Y P s y c h o l o g y D e p a r t m e n t , U n i v e r s i t y o f British C o l u m b i a Vancouver, B.C., Canada, V6T 1W5 R e c e i v e d 26 J a n u a r y 1979 ALBERT, D. J. AND K. N. BRAYLEY. Mouse killing and hyperreactivity following lesions of the medial hypothalamus, the lateral septum, the bed nucleus of the stria terminalis, or the region ventral to the anterior septum. PHYSIOL. BEHAV. 23(3)439--443, 1979.--Electrolytic lesions in the medial hypothalamus, the lateral septum, or the region ventral to the anterior septum induced home cage mouse killing in 85 to 100% of rats when tested 2 days postoperatively and in 50 to 70% when tested at 21 days. When tested in a novel and larger test chamber, 100% of the rats with medial hypothalamic lesions killed mice at 2 days postoperatively but only 30% killed at 21 days postoperatively. Ten to thirty percent of animals with lesions of the lateral septum or of the region ventral to the anterior septum killed at any time in the novel environment. Lesions of the stria terminalis produced a slight increase in mouse killing in both the home cage and the novel environment. A high level of reactivity was produced by lesions of the medial hypothalamus, the lateral septum or the region ventral to the anterior septum but only that caused by the medial hypothalamic lesions was sustained over the 21 day test period. These results support previous evidence that the lateral septum, the region ventral to the anterior septum, and the medial hypothalamus are each important areas modulating mouse killing. Aggression
Lateral septum
Medial hypothalamus
MOUSE killing is increased by electrolytic lesions in the medial hypothalamus, the septum, and the stria terminalis. It occurs in 30 to 50% of rats with lesions of the medial hypothalamus [5, 6, 9]. In contrast, lesions of the medial and lateral septum have induced mouse killing in 100% of rats in one experiment but in only 12% in another [6,7]. Stria terminalis lesions appear to slightly augment mouse killing particularly when the rats are food deprived [14], yet lesions of the bed nucleus of the stria terminalis reportedly are without effect [8]. These studies suggest that the septum and the medial hypothalamus may not be equally involved in the modulation of mouse killing and that the stria terminalis may be involved in yet a quite different way. However, the validity of these conclusions is difficult to evaluate because the experiments have been conducted differently and, in addition, the size of the lesions in each area have been quite variable. Recent
Mouse killing
Reactix,ity
Stria terminalis
work using temporary chemical lesions purports to have localized the regions in the septal area [4] and the medial hypothalamus [3] which are involved in modulating mouse killing. In addition, an area ventral to the anterior septum has been found to modulate mouse killing [4]. Accordingly, it now seems possible to compare the effect of electrolytic lesions in these various areas in a single study using a common procedure and where the tissue thought to be involved in modulating mouse killing in each area is consistently removed. The present experiments compared the effect on mouse killing of lesions at four sites: the medial hypothalamus, the lateral septum, the region ventral to the anterior septum, and the bed nucleus of the stria terminalis. Mouse killing was examined both in the home cage and in a novel test chamber at various intervals following the lesions. The effect of each lesion on reactivity to the experimenter was also examined.
~Supported by a grant from the National Research Council of Canada. Reprint requests to: D. J. Albert, Psychology Department, University of British Columbia, Vancouver, B.C., Canada V6T IW5.
C o p y r i g h t © 1979 B r a i n R e s e a r c h P u b l i c a t i o n s Inc.--0031-9384/79/090439-05501.00/0
440
ALBERT AND BRAYI.EY METHOD
Animals The animals were 41 male hooded rats weighing 350-450 g (Canadian Breeding Farms and Laboratories, Quebec, Canada). They were housed in group cages prior to surgery and in individual cages thereafter.
ttistology Following behavioral testing the brains of all animals were removed and placed in formol-saline. They were later sectioned on a cryostat and stained with cresyl violet. RESU LTS
Mouse Killing Surgical Procedure The animals were divided into five groups according to the intended location of their lesions. Bilateral DC lesions were made using a stainless steel electrode (0.5 mm dia.) connected to the anode and the cathode attached to the tall. The hypothalamic coordinates were: anterior to bregma 0.0 ram, lateral 0.7 mm, ventral to the cortical surface 9.0 mm (DeGroot c.oordinates; 2.0 mA, 30 sec). Bilateral lesions ventral to the anterior septum (2.0 mA, 25 sec) were made at 2.9 mm anterior to bregma, 1.2 mm lateral to the midline, and 6.8 mm ventral to the cortical surface. Bilateral lesions of the bed nucleus of the stria terminalis (2.0 mA, 20 sec) were located 1.1 mm anterior to bregma, 1.3 mm lateral, and 5.7 mm ventral to the cortical surface. Bilateral lesions were made at two sites in the lateral septum of each animal. The coordinates for the first were: 1.6 mm anterior to bregrna, 0.7 mm lateral, and 4.5 mm ventral to the cortical surface. The second lesion was made at 2.3 mm anterior to bregma, 0.7 mm lateral, and 4.5 mm ventral to the cortical surface (both lesions were made with 2.0 mA, 25 sec). Animals in the control group had electrodes lowered at one of these lesion sites but no current was passed.
Behavioral Testing All animals were tested for muricide and reactivity on postoperative Days 2, 7, 14, and 21. Muricide was examined by putting a white albino mouse (about 35 g) into the rat's living cage (17x24x 17 cm high) for 5 min and recording the latency to kill. Reactivity was measured at 1 hr following the muricide test in a 6 0 x 6 0 x 6 0 cm high box with gray walls, an open top, and wood shavings on the floor. Testing was done in the animal's colony area. The animal was dumped from its living cage onto the floor of the test chamber and then allowed to explore for 5 min before the reactivity test began. The reactivity test has been described in detail previously [2]. Briefly, the animal is given a score of 0 to 3 (0 indicating little or no response, and 3 indicating a highly aggressive or reactive response) for its response to each of 6 stimuli (presentation of a pencil, a tap on the back, presentation of a gloved hand, a poke in the side, grasping by the tail, and grasping by the abdomen) and on the amount of vocalization and amount of biting observed during testing [2, 3, 4]. The maximum score possible is 24. Immediately following the reactivity test, each rat that had killed a mouse in its home cage was given a 5 min test for muricide in the less familiar surroundings of the reactivity test chamber. Only animals that had killed in the home cage were tested for mouse killing in the chamber because preliminary experiments showed that mouse killing in the novel test chamber is very unlikely to occur in animals that have not killed in the home cage. Latency to kill was again recorded.
Lesions of the medial hypothalamus (N =7), the region ventral to the anterior septum (N=8) or the lateral septum (N=8) each produced a high percentage of killers in the home cage muricide test (Fig. 1). The proportion of killers in each group was reliably greater than in the control group at each test interval (Fisher's exact probability tests, all p ' s < 0 . 0 5 ; all p-values are two-tailed unless indicated). The latency to kill for the animals which killed was similar in each of these groups (10 to 20 sec). Stria terminalis lesions (N =5) produced a greater frequency of muricide than the sham lesions only on the first day (Day 2; p
