Physiology & Behavior, Vol. 23, pp. 803-806. Pergamon Press and Brain Research Publ., 1979. Primed in the U.S.A
Impaired Patterned Responding in Rats With Electrolytic Median Raphe L e s i o n s I K A R E N E. A S I N , D A V I D W I R T S H A F T E R A N D E R N E S T W. K E N T
University of Illinois--Chicago Circle, Department of Psychology, P.O. Box 4348, Chicago, IL 60680 Received 25 March 1979 ASIN, K. E., D. WIRTSHAFTER AND E. W. KENT. Impaired patterned responding in rats with electrolytic median raphe lesions. PHYSIOL. BEHAV. 23(4) 803-806, 1979.--Rats with electrolytic lesions of the median nucleus of the raphe were severely impaired in the acquisition of a straight alley, single alternation response compared to sham operated controls. This deficit was due to the failure of lesioned animals to reduce their running speeds on non-reinforced trials. As similar results have been obtained following damage to several limbic structures, this study provides behavioral evidence for the concept of a limbic midbrain circuit.
Median raphe nucleus
Patternedresponding
Singlealternation
NAUTA [15] has used the term limbic midbrain circuit to refer to the system of profuse interconnections between the limbic system and the paramedian tegmentum of the midbrain, an area which he labels the limbic midbrain region. Although anatomical studies suggest that this region may play an important role in the functioning of the forebrain limbic system [15], there have been few attempts to determine if there are any similarities between the behavioral effects of midbrain and limbic lesions. Electrolytic lesions of the median nucleus of the raphe, a component of Nauta's limbic midbrain region, lead to perseverative responding in tests of spontaneous alternation [1,9] and we have recently observed that these lesions impair the extinction of a foodrewarded straight alley task [2]. Similar results have been reported following lesions of limbic structures, including the hippocampus, septum, and, in the case of impaired alley extinction, the cingulate gyrus [5, 6, 10, 12, 17]. In view of these similarities between the effects of median raphe and limbic lesions, the current study was undertaken to investigate the role of the median nucleus of the raphe in the acquisition of a straight alley single alternation response. The acquisition of this task has shown to be impaired following damage to several limbic structures in the rat [3, 7, 18]. METHOD
Animals Animals were seventeen male, Sprague-Dawley derived rats obtained from a colony maintained by the University of Illinois. Animals weighed 300 _+ 15 g at the time of surgery and were individually housed under conditions of constant illumination; water was available ad lib. Nine randomly selected rats received electrolytic raphe lesions and the remainder were sham operated
Limbicmidbrain circuit
Serotonin
Surgical Procedures Surgery was performed under sodium pentobarbitol anesthesia (50 mg/kg IP). A stainless steel electrode, 0.23mm in diameter and insulated except for 0.5mm at the tip, was placed stereotaxically at coordinates [16]: AP: +.2, Lat: 0 H: -4.3, and a 1 mA current was passed for 8 see through a rectal cathode. In sham operated animals, burr holes were drilled and the mid-saggital sinus was punctured, but the electrode was not lowered.
Apparatus and procedure The alley was constructed of clear Plexiglas except for the floor, which was composed of metal rods 2 mm in diameter, spaced 10ram apart. The alley was partitioned by metal guillotine doors to form a start box (16x 11.5x 10 era), a runway (110 x 15 × 10 cm) and a goal box (30.3 x 15 x 10 era). Latencies were measured to the nearest one-hundredth of a second by the use of two photocells situated 14 and 103 cm from the start box which were connected to a Hunter Klockounter. A single Froot Loop (Kellogs) was placed in a small glass coaster in the rear of the goal box on rewarded trials. Beginning ten days following surgery, rats were maintained on a restricted feeding schedule which reduced them to approximately 85% of their free-feeding weight. After eight days on the diet, rats were placed in the alley and were allowed to explore it for 5 min; the following day they were confined to the goal box until thay had consumed a Froot Loop placed in the coaster. The next day, acquisition training was begun. Each rat was placed in the start box of the alley facing away from the lowered guillotine door. This door was raised when the animal oriented toward it. After the animal had left the start box the door was lowered to prevent retracing. After the animal had entered the goal box the door to that compartment was
1Portions of this study were presented at the Seventh Annual Meeting of the Society for Neuroscience, 1977.
Copyright © 1979 Brain Research Publications Inc.--0031-9384/79/100803-03500.80/0
804
A S I N , W I R T S H A F T E R AND KEN1
FIG. 1. Photograph of an unstained brain showing a typical electrolytic lesion of the median raphe. lowered and the rat was allowed to consume the reward or, in the case of non-rewarded trials, was retained in the goal box for 10 sec. He was then removed from the apparatus, placed in a holding cage, and run again 1 minute later, for a total of 10 trials per day. On the first day of acquisition, animals were reinforced every time they entered the goal box. F o r the following 22 days, rats were reinforced only on odd numbered trials. Any animal which failed to enter the goal box within 30 sec was placed in the goal box for ten seconds (such failures to enter the goal box occurred only in control animals on nonreinforced trials during the last 10 days of training).
1.25
~ i A
MR-R
A,e~w,A MR - N M
~ .75.
•2 5 .
f
"",.
RESULTS A photograph of a typical lesion is shown in Fig. 1. In all cases the lesions severely damaged the median raphe and the immediately adjacent reticular formation. The ventral tegmental nuclei of Gudden and and the nuclei reticularis tegmenti pontis were never involved. Figure 2 displays mean running speeds (l/latency) for lesioned and control animals across the 22 days of alternation training. Individual t-tests demonstrated that control animals ran significantly faster on reinforced than on nonreinforced trials during Days 15-22 of training (0.001< p 0.25) A 2×2 (lesion × reinforced condition) repeated measures analysis of variance conducted on mean running speeds across the last 5 days of training indicated a signi-
• 1
g
• 3
•
• 5
•
• 7
•
• 9
•
• • 11 DAYS
• 13
•
• 15
•
e 17
•
• 19
•
I 21
|
FIG. 2. Mean running speeds (1/latency) across twenty-two days of acquisition training of median raphe lesioned (MR) and control (CONT) rats on reinforced (-R) or non-reinforced ( - N ) trials.
ficant lesion x reinforcement condition interaction, F(1,15)=18.7, p
Impaired Patterned Responding in Rats With Electrolytic Median Raphe L e s i o n s I K A R E N E. A S I N , D A V I D W I R T S H A F T E R A N D E R N E S T W. K E N T
University of Illinois--Chicago Circle, Department of Psychology, P.O. Box 4348, Chicago, IL 60680 Received 25 March 1979 ASIN, K. E., D. WIRTSHAFTER AND E. W. KENT. Impaired patterned responding in rats with electrolytic median raphe lesions. PHYSIOL. BEHAV. 23(4) 803-806, 1979.--Rats with electrolytic lesions of the median nucleus of the raphe were severely impaired in the acquisition of a straight alley, single alternation response compared to sham operated controls. This deficit was due to the failure of lesioned animals to reduce their running speeds on non-reinforced trials. As similar results have been obtained following damage to several limbic structures, this study provides behavioral evidence for the concept of a limbic midbrain circuit.
Median raphe nucleus
Patternedresponding
Singlealternation
NAUTA [15] has used the term limbic midbrain circuit to refer to the system of profuse interconnections between the limbic system and the paramedian tegmentum of the midbrain, an area which he labels the limbic midbrain region. Although anatomical studies suggest that this region may play an important role in the functioning of the forebrain limbic system [15], there have been few attempts to determine if there are any similarities between the behavioral effects of midbrain and limbic lesions. Electrolytic lesions of the median nucleus of the raphe, a component of Nauta's limbic midbrain region, lead to perseverative responding in tests of spontaneous alternation [1,9] and we have recently observed that these lesions impair the extinction of a foodrewarded straight alley task [2]. Similar results have been reported following lesions of limbic structures, including the hippocampus, septum, and, in the case of impaired alley extinction, the cingulate gyrus [5, 6, 10, 12, 17]. In view of these similarities between the effects of median raphe and limbic lesions, the current study was undertaken to investigate the role of the median nucleus of the raphe in the acquisition of a straight alley single alternation response. The acquisition of this task has shown to be impaired following damage to several limbic structures in the rat [3, 7, 18]. METHOD
Animals Animals were seventeen male, Sprague-Dawley derived rats obtained from a colony maintained by the University of Illinois. Animals weighed 300 _+ 15 g at the time of surgery and were individually housed under conditions of constant illumination; water was available ad lib. Nine randomly selected rats received electrolytic raphe lesions and the remainder were sham operated
Limbicmidbrain circuit
Serotonin
Surgical Procedures Surgery was performed under sodium pentobarbitol anesthesia (50 mg/kg IP). A stainless steel electrode, 0.23mm in diameter and insulated except for 0.5mm at the tip, was placed stereotaxically at coordinates [16]: AP: +.2, Lat: 0 H: -4.3, and a 1 mA current was passed for 8 see through a rectal cathode. In sham operated animals, burr holes were drilled and the mid-saggital sinus was punctured, but the electrode was not lowered.
Apparatus and procedure The alley was constructed of clear Plexiglas except for the floor, which was composed of metal rods 2 mm in diameter, spaced 10ram apart. The alley was partitioned by metal guillotine doors to form a start box (16x 11.5x 10 era), a runway (110 x 15 × 10 cm) and a goal box (30.3 x 15 x 10 era). Latencies were measured to the nearest one-hundredth of a second by the use of two photocells situated 14 and 103 cm from the start box which were connected to a Hunter Klockounter. A single Froot Loop (Kellogs) was placed in a small glass coaster in the rear of the goal box on rewarded trials. Beginning ten days following surgery, rats were maintained on a restricted feeding schedule which reduced them to approximately 85% of their free-feeding weight. After eight days on the diet, rats were placed in the alley and were allowed to explore it for 5 min; the following day they were confined to the goal box until thay had consumed a Froot Loop placed in the coaster. The next day, acquisition training was begun. Each rat was placed in the start box of the alley facing away from the lowered guillotine door. This door was raised when the animal oriented toward it. After the animal had left the start box the door was lowered to prevent retracing. After the animal had entered the goal box the door to that compartment was
1Portions of this study were presented at the Seventh Annual Meeting of the Society for Neuroscience, 1977.
Copyright © 1979 Brain Research Publications Inc.--0031-9384/79/100803-03500.80/0
804
A S I N , W I R T S H A F T E R AND KEN1
FIG. 1. Photograph of an unstained brain showing a typical electrolytic lesion of the median raphe. lowered and the rat was allowed to consume the reward or, in the case of non-rewarded trials, was retained in the goal box for 10 sec. He was then removed from the apparatus, placed in a holding cage, and run again 1 minute later, for a total of 10 trials per day. On the first day of acquisition, animals were reinforced every time they entered the goal box. F o r the following 22 days, rats were reinforced only on odd numbered trials. Any animal which failed to enter the goal box within 30 sec was placed in the goal box for ten seconds (such failures to enter the goal box occurred only in control animals on nonreinforced trials during the last 10 days of training).
1.25
~ i A
MR-R
A,e~w,A MR - N M
~ .75.
•2 5 .
f
"",.
RESULTS A photograph of a typical lesion is shown in Fig. 1. In all cases the lesions severely damaged the median raphe and the immediately adjacent reticular formation. The ventral tegmental nuclei of Gudden and and the nuclei reticularis tegmenti pontis were never involved. Figure 2 displays mean running speeds (l/latency) for lesioned and control animals across the 22 days of alternation training. Individual t-tests demonstrated that control animals ran significantly faster on reinforced than on nonreinforced trials during Days 15-22 of training (0.001< p 0.25) A 2×2 (lesion × reinforced condition) repeated measures analysis of variance conducted on mean running speeds across the last 5 days of training indicated a signi-
• 1
g
• 3
•
• 5
•
• 7
•
• 9
•
• • 11 DAYS
• 13
•
• 15
•
e 17
•
• 19
•
I 21
|
FIG. 2. Mean running speeds (1/latency) across twenty-two days of acquisition training of median raphe lesioned (MR) and control (CONT) rats on reinforced (-R) or non-reinforced ( - N ) trials.
ficant lesion x reinforcement condition interaction, F(1,15)=18.7, p
