Operant responding in rats with posterior midline cortical lesions

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Brain Research, 125 (1977) 356-361 © Elsevier/North-Holland Biomedical Press, Amsterdam - Printed in The Netherlands

Operant responding in ,rats with posterior midline cortical lesions

R O D E R I C K M. COOPER, ROBERT J. F E R R I E R and M U R R A Y P. B I R C H

Department of Psychology, University of Calgary, Calgary, Alberta T2N 1N4 (Canada) (Accepted January 17th, 1977)

Damage to limbic system brain structures causes abnormal operant responding on intermittent schedules of reinforcement. Animals with septal lesions bar press at higher rates on fixed interval (FI), variable interval (VI) and differential reinforcement of low rate (DRL) schedules1,2,9-11; animals with hippocampal lesions also lever press at higher-than-normal rates on VI and D R L scheduleslS,1L (On the FI schedule an operant response is reinforced only after a fixed interval of time, while VI schedules vary the interval length between reinforced responses, around a predetermined average time interval. On D R L schedules, the subject must delay the operant response for a fixed time period to obtain reinforcement.) Such findings are well substantiated in the literatureS,12,1L However, posterior cingulate and retrosplenial cortex, long considered integral to limbic circuitry 14,17, can apparently be ablated without affecting operant behavior in such tasks ~,4,~3. The present work suggests that this apparent discrepancy simply reflects unsuitable lesion placement, and that disruption of intermittent reinforcement schedule responding may be a sine qua non of limbic system damage. Our experiments indicate that lesions to very caudal posterior midline cortex (which apparently suffered little damage in previous studies) do cause defective operant behavior on intermittent reinforcement schedules. The work developed from studies of rats given large posterior cortical lesions. The visual areas and adjacent cortex had both been extirpated; thus the abnormally high VI-30 sec bar pressing rates displayed might have reflected midline tissue damage. Results of our first experiment supported such a hypothesis. Experiment 1 compared bar pressing rates on 'CRF' ('continuous reinforcement', whereby every bar press is reinforced) and VI reinforcement schedules, for 'normal', 'midline' and 'lateral' rats. Each group consisted of 10 animals. The 'normal' group remained unoperated, while the 'midline' and 'lateral' groups underwent removal of the medial and lateral posterior two-thirds of the cortex respectively, under deep sodium pentobarbital anesthesia. Fig. 2 illustrates the lesions made in midline and lateral animals. After a 49 day recovery period, subjects were food deprived to 80 ~ of their body weights, then trained in Skinner boxes with levers requiring a 20 g depression force. On day 1 of box exposure, the animals were trained to press on CRF until

357 they had received about seventy 45 mg food pellets. The next day, one-half of each group continued on CRF while the other half began VI training. After several sessions, rats trained on CRF were switched to the VI schedule and those trained on the VI schedule were placed on C R F (see Fig. 1). A daily testing session ended when an animal had earned 70 pellets. Fig. 1 reveals that midline subjects pressed at higher VI rates than either the lateral or normal animals. (Fig. 1 also implies that lateral animals were abnormal, since their VI rates reached asymptote sooner than normal subjects. However, no such effect appeared in later experiments.) Fig. 1 also shows that C R F rates for both lesion groups were indistinguishable, with both responding at a lower rate than normal subjects. We tentatively ascribe this difference to a lesion-induced eatingimpairment: a separate test showed that lateral and midline animals could not consume food pellets as rapidly as normal animals. The data were viewed as support for our suspicion that destruction of posterior midline cortex, like destruction of other limbic areas, disposes subjects to overrespond on VI schedules. In experiment 2 additional groups of cortically lesioned animals were included for more precise location of the critical lesion site. Fifty-one days after surgery, all 6 groups of 8 rats were trained on the VI-30 sec schedule as in experiment 1, except that daily testing sessions ended after 1 h rather than after collection of 70 food pellets. As in experiment 1, midline rats pressed at higher rates than either the normal (given 'sham' surgery) or the lateral animals. Of special interest are the 3 additional lesion groups. Two groups received midline lesions equal in rostrocaudal

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Fig. 2. Frontal sections from brains of rats sustaining different cortical lesions. In columns, from left to right, brains with: midline, lateral, midline M, midline P and striate lesions. length to roughly half that of the midline group. Thus, the 'midline M' group sustained lesions in the middle third of midline cortex, while 'midline P' animals received lesions to the most caudal third (Fig. 2). F and t tests showed that the midline and midline P groups did not differ significantly from each other in VI pressing rate, but that both pressed more than the normal sham, midline M and lateral groups, whose rates were all similar. Thus the overresponding effect appears to depend on destruction of the more caudal region of midline cortex. In addition, the abnormally low VI rate of the 'striate' group (Fig. 2) implies that the critical lesion locus fails to encroach on area 17, and is confined to the midline region. In experiment 3 the posterior midline deficit was further explored by applying a DRL-20 sec reinforcement schedule to the animals tested in experiment 2. Results, summarized in Fig. 3, parallel the VI data from experiment 2 : the midline and midline P animals bar pressed more (thus earning fewer pellets on D R L ) than all the other groups. Results for experiments 1-3 indicated that posterior midline, like septal and hippocampal lesions, produce an overresponding impairment on VI and D R L

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schedules. This tendency can apparently be corrected under certain conditions: Ellen and Butter 9 used a cue light to signal the end of delay periods on a D R L schedule, and rats with septal lesions then earned as many reinforcements as control animals. Experiment 4 examined whether posterior midline animals would similarly benefit from such a cue. The midline, midline P and normal sham groups of experiment 3 served as subjects for experiment 4. H a l f of each group remained on an uncued version of the DRL-20 sec schedule. For the other half, a light came on after the 20 sec delay, and stayed on until a lever press occurred. After five 1 h sessions, the cue condition was switched for the 6 subgroups and testing continued for another 8 sessions. Fig. 4 shows the number of pellets earned by the 3 groups on the two versions of the task. Like septal rats, the midline and midline P subjects soon succeeded in collecting as many pellets as normal sham animals, on the cued version of the task only. The study implies that the rat's posterior midline cortex is 'limbic' in function. Lesions in the region mimic the effects of septal and hippocampal lesions - - increased VI rates, and impaired D R L performance corrected when an overt cue designates the end of required delays. K a a d a 16 has also reported similarities between septal and posterior midline cortical regions • he found respiration inhibited both by stimulation of the septal and retrosplenial areas. Designating posterior midline cortex as limbic in function may seem inconsistent

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Fig. 4. Experiment 4: pellets earned by midline, midline P and normal sham rats on light-cued and regular versions of DRL task. Left, groups receivedregular DRL followed by cued DRL; on the right, groups received cued DRL followed by regular DRL sessions. with certain previous studies. Thomas and his collaborators 3,4,13 claim that posterior midline lesions do not alter performance on tasks typically disrupted by limbic damage. However, the present study suggests their lesions were not placed far enough posterior to demonstrate the deficit: their lesions apparently resembled those of experiment 3 midline M animals, which performed normally on VI and D R L schedules. The cingulum bundle was largely destroyed in both the midline M and midline P animals, but behavioral signs of limbic damage only appeared in the latter group. This implies that overresponding results from destruction of posterior midline cortex per se rather than from cingulum damage. However, Domesick's 5-7 assertion, that midline cortex has far fewer connections to other limbic structures than Papez suggested, challenges the designation ofmidline cortex as a limbic component. Domesick proposes that the classical Papez view arose spuriously from anatomical work involving damage to the cingulum bundle, which contains thalamic projection fibers that bypass midline cortex. However, the difference in behavioral effects between anterior and posterior lesions noted in our study implies that Domesick's work should be extended with emphasis on posterior midline cortex. While the present results may endorse an overresponding tendency as a sine qua non behavioral consequence of limbic damage, recent work by Ross and Grossman is suggests a different possibility. Although they found that severing the fornix, a major route between septum and hippocampus, produces overresponding, severing the median forebrain bundle connecting the septal area and hypothalamus had no such

361 effect. Thus, h i p p o c a m p a l d y s f u n c ti o n m ay be the seat o f o v e r r e s p o n d i n g tendencies. Since midline cortex is considered an i m p o r t a n t c o n t r i b u t o r to h i p p o c a m p a l function 14, o u r results are c o m p a t i b l e with this conclusion. This study was s u p p o r t e d by a C a n a d i a n N R C G r a n t APA-135.

1 Aaron, M. and Thorne, B. N., Omission training and extinction in rats with septal damage, Physiol. Behav., 15 (1975) 149-154. 2 Atnip, G. and Hothersall, D., Response suppression in normal and septal rats, PhysioL Behav., 15 (1975) 417-421. 3 Barker, D. J., Alternations in sequential behavior of rats following ablation of midline limbic cortex, J. comp. physiol. Psychol., 64 (1967) 453-460. 4 Barker, D. J. and Thomas, G. J., Effects of regional ablation of midline cortex on alternation learning by rats, PhysioL Behav., 1 (1966) 313-317. 5 Domesick, V. B., Projections from the cingulate cortex in the rat, Brain Research, 12 (1969) 296-320. 6 Domesick, V. B., The fasciculus cinguli in the rat, Brain Research, 20 (1972) 19-32. 7 Domesick, V. B., Thalamic projections in the cingulum bundle to the parahippocampal cortex of the rat, Anat. Rec., 175 (1972) 308 (abstract). 8 Douglas, R. J., The hippocampus and behavior, Psychol. Bull., 67 (1967) 416~42. 9 Ellen, P. and Butter, J., External cue control of DRL performance in rats with septal lesions, Physiol. Behav., 4 (1969) 1-6. 10 Ellen, P. and Powell, E. W., Effects of septal lesions on behavior generated by positive reinforcement, Exp. Neurol., 6 (1962) 1-11. 11 Ellen, P., Wilson, P. and Powell, E. W., Septal inhibition and timing behavior in the rat, Exp. Neurol., 10 (1964) 120-132. 12 Fried, P. A., Septum and behavior: a review, PsyehoL Bull., 78 (1972) 292-310. 13 Glass, D. H., Ison, J. R. and Thomas, G. J., Anterior limbic cortex and partial reinforcement effects on acquisition and extinction of a runway response in rats, J. comp. physioL PsychoL, 69 (1969) 17-24. 14 Hall, E., The anatomy of the limbic system. In G. J. Mogenson and H. R. Calarescu, Neural Integration of Physiological Mechanisms and Behavior, University of Toronto Press, Toronto, 1975, pp. 68-94. 15 Jarrard, L. E., Hippocampal ablation and operant behavior in the rat,Psychon. Sci., 2 (1965) 115-116. 16 Kaada, B. R., Cingulate, posterior orbital, anterior insular and temporal pole cortex. In J. Field (Ed.), Handbook o f Physiology, Section 1, Neurophysiology, 1Ioi. 2, American Physiological Society, Washington, D.C., 1960, pp. 1345-1372. 17 Papez, J. W., A proposed mechanism of emotion, Arch. NeuroL Psychiat. (Chic.), 38 (1937) 725-744. 18 Ross, J. F. and Grossman, S. P., Septal influences on operant responding in the rat, J. comp. physioL Psychol., 89 (1975) 523-536. 19 Schmaltz, L. W. and Isaacson, R. L., Retention of a DRL 20 schedule by hippocampectomized and partially neodecorticate rats, J. comp. physioL PsychoL, 62 (1966) 128-132.