Locomotor, avoidance and maze behavior in rats with the dorsal fornix transected

Physiology and Behavior, Vol. 14, pp. 847-853. Brain Research Publications Inc., 1975. Printed in the U.S.A.

Locomotor, Avoidance and Maze Behavior in Rats with the Dorsal Fornix Transected I TROND MYHRER AND BIRGER KAADA

Institute o f Neurophysiology, University o f Oslo, Oslo, Norway

(Received 12 November 1974) MYHRER, T. AND B. KAADA. Locomotor, avoidance and maze behavior in rats with the dorsal fornix transected. PHYSIOL. BEHAV. 14(6) 847-853, 1975. - Transection of the dorsal fornix bundle in rats resulted in impaired maze learning, while the behavior in open field, passive avoidance and spontaneous alternation test was unchanged. The results are discussed in terms of an association deficit. It is concluded that the dorsal fornix is probably not to be regarded as part of the hippoeampal output system. Dorsal fornix

Rat

Open field

Passiveavoidance

Hebb-Williamsmaze

THE dorsal fornix in rats is a well-defined bundle of axons which increases in size as it courses rostrally close to the midline between the corpus callosum and the hippocampal commissures. The fibers are distributed mainly through the post-commissural fornix to the anterior thalamic nuclei and the mamillary bodies [32]. The close relationship between the dorsal fornix and the mamillary bodies has also been observed by Guillery [15] and Cragg and Hamlyn [6,7]. The fibers of the dorsal fornix have been reported to arise largely in the subiculum [4, 6, 26] and in the area CA1 of the hippocampus [6, 8, 29, 31, 32]. However, recent histological [ 17 ] as well as electrophysiological data [ 1 ] suggest that the CA1 pyramidal cells project to the subiculum only. In addition to the fibers originating in the subiculum, a system of ventro-rostrally directed fibers has been reported in a number of species to perforate the corpus callosum from above (from the splenium towards the genu) and then to join the longitudinal fibers of the dorsal fornix [6, 11, 26]. The origin of these perforating fibers has primarily been attributed to the cingulate cortex [6, 13, 26] and the retrosplenial cortex [6], but to the subiculum [26] and the cingulum fibers as well [4]. The perforating fibers have been traced by some investigators into the septal area [13,26]; however, others have been able to follow the fibers only as far as the post-commissural fornix [6]. The main purpose of this study was to investigate whether the dorsal fornix contains hippocampal CA1 output. Rats with damage to the subfield CA1 are more active in open field test than control animals, but no significant differences are seen in passive avoidance, maze learning or alternation behavior [28]. These behaviors were tested in the present study in dorsal fornix-lesioned rats. Another object of this study was to assess the behavioral importance of the perforating fibers. To study this

Spontaneous alternation

question, the dorsal fornix was severed at a rostral and a caudal level in two groups of rats (Fig. 1A). Differences in behavior between the two groups may then be attributed to lesion of the perforating fibers joining the dorsal fornix between the two levels of transection. By means of the present approach, an attempt was also made to elucidate some of the contradictory results reported after hippocampal lesions. Contradictions may be due, at least in part, to damage of structures adjoining the hippocampus, such as the dorsal fornix. GENERAL METHOD

Animals Thirty-three male albino rats of the M¢ll Wistar strain, weighing 2 5 0 - 3 0 0 g at the time of surgery, were randomly assigned to 4 groups: 8 animals received bilateral division of the dorsal fornix at a rostral level and 8 at a caudal level, 8 received control lesions (cf. below), and 9 served as normal controls. The rats were housed in groups of 3 and fed commercial rat pellets and water ad lib, except for a later described deprivation. Rats from different groups were housed together, and their group assignment was not known during testing. The room containing the cages was kept on a 1 2 - 1 2 hr reversed day/night cycle.

Surgery The animals were anesthetized with sodium pentobarbital (60 mg/kg) and placed with flat skull in a stereotaxic head holder. Lesions were produced mechanically with the sharp edges of a cannula that was mounted on a syringe and provided with a small adjustable collar. The cannula was inserted through a small hole drilled in the

1This research was supported by the Norwegian Research Council for Science and the Humanities. 847

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MYHRER AND KAADA

skull to the depth permitted by the collar. Since the dorsal fornices course close to the midline, both could be reached with the cannula from one side; care being taken not to destroy the superior sagittal sinus and the cingulum bundle. In one group of rats (designated DF-I), the dorsal fornix was divided at a rostral level corresponding to the fornix-septum junction, 0.5 mm posterior to the bregma and 0.5 mm lateral to the midline. The cannula was inserted in a vertical position 5 mm below the surface of the skull. From this position the tip of the needle was moved 1 . 5 - 2 . 0 mm to the opposite hemisphere with the sharp edges in the frontal plane. In a second group of animals (designated DF-II), the dorsal fornix was sectioned at a caudal level, corresponding to posterior part of the dorsal hippocampal commissure. The cannula was introduced 4.8 mm posterior to the bregma, 0.5 mm lateral to the midline and to a depth of 4 mm from surface of the skull. From a vertical position the tip of the needle was moved about 2 mm to the opposite hemisphere. Animals assigned to the lesioned control group received similar treatment except that the needle was lowered only 3.5 mm or 2.5 mm corresponding to level I (4 rats) and level II (4 rats) respectively. The normal control animals received an incision in the scalp only.

A

B

DFI

DFII

C

Histology At termination of the testing all lesioned rats were sacrificed and the brains removed, fixed in Formalin and embedded in paraffin. Serial sections (16 u thick) from the area of the lesion were prepared, and every third section was stained with thionin. The dorsal fornices were found to be completely transected at the rostral level I in all 8 animals (Fig. 1B). In addition to lesion in the target area, only minor additional damage could be observed in the neocortex and in the corpus callosum. Four rats assigned to the lesioned control group with insertions at level I had no damage other than a small track in the neocortex. At the caudal level II the dorsal fornix also appeared to be completely severed bilaterally in all 8 rats (Fig. 1C). Additional damage accompanying these lesions was observed as a slight track in the neocortex and a narrow cut in the corpus callosum, the dorsal hippocampal commissure and the most dorso-medial portions of the presubiculum. Since the two cingulum bundles join in the area of level II, some cingulum fibers (less than 10 percent) close to the midline were damaged. In addition, the ventro-medial portion of the cingulum was lesioned unilaterally in 5 animals o f the DF-II group. Among the 4 rats with control lesions at level II, only a track in the neocortex was observed in 2 of them. In the remaining 2 animals, a small portion of the cingulum had been damaged on one side.

FIG. 1. Diagram of a sagittal section showing the two sites of dorsal fornix transection (A). Examples of DF-I lesion (B) and DF-II lesion (C). Abbreviations: cc = corpus callosum; fo = fornix; hipp = hippocampus.

Method A Hebb-Williams closed field maze described elsewhere [27], was used as the open field. In short, the open field consisted of a square floor (96 cm) divided in 36 equal squares. The entire apparatus was covered by a 73 cm high pyramidal-shaped enclosure with observation windows. A 40 W bulb was located in the apex of the pyramid. A start box (22 × 14 x 9 cm) was placed in one corner. The floor and the inside of the enclosure were painted white and all other components were black. The rats were tested individually for 2 min each day for 4 consecutive days, starting on Postoperative Day 12. The animals were placed in the start box, and the latency of entering the field was measured. The pattern of running was traced on section paper, and the number of squares traversed was used as an activity measure. The number of fecal boluses dropped in the field and the start box was recorded.

Results EXPERIMENT 1: OPEN FIELD Several authors have demonstrated augmented activity in open field tests as a result of hippocampal lesions [3, 10, 20, 23, 25, 35], while others have failed to reveal such effects [2,18]. These conflicting results may have resulted from additional section of the dorsal fornix which has often been severed in the reported experiments, in particular those dealing with dorsal hippocampal lesions.

The DF-II group traversed twice as many squares as did the DF-I group and the two control groups (Table 1). Model I analysis of variance [ 16] yielded significant treatment effect, F(3,29) = 4.4, p<0.025. Mean comparisons with two-tailed t test revealed that the DF-II group was significantly more active than both control groups (p< 0.02) and the DF-I group (p<0.05). Neither control group had significantly different activity measures, nor did they differ from the DF-I group.

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DORSAL FORNIX AND BEHAVIOR TABLE 1 MEANS AND STANDARD ERRORS OF OPEN FIELD MEASURES BASED ON AVERAGE SCORES FOR 4 DAYS No. Squares Traversedin Entire Field

No. Squares Traversedin Interior Field

Group

N

Start Box Exit Latency in Sec

DF-I

8

31.6 -+ 28.7

11.1 ± 11.0

0.4 ± 0.6

1.7 ± 1.3

DF-II

8

15.5 ± 16.4

27.8 ± 17.7

1.1 ± 1.5

2.2 ± 1.8

L Cont

8

42.0 ± 31.1

8.3 +- 8.3

0.1 ± 0.4

1.8 ± 1.0

Normal

9

56.5 ± 44.8

8.1 ± 12.2

0.2 -+ 0.3

1.8 ± 1.5

Analysis of the running pattern revealed that the DF-II animals tended to enter more squares outside the perimeter of the open field than both categories of control rats (Table 1). However, analysis of variance did not yield a significant treatment effect. No reliable differences occurred among the groups in start box exit latency or defecation (Table 1). Discussion Transection of the dorsal fornix at level II resulted in increased open field activity, whereas level I lesion did not do so at a statistical significantly level. The difference in performance between the two experimental groups might be due to additional damage to the cingulum fibers and/or the dorso-medial portion of the presubiculum among the DF-II animals. An interaction effect caused by lesions of the dorsal fornix, cingulum fibers and presubiculum could be responsible for the behavioral change. For anatomical reasons an investigation of the effects of selective lesion of these three components at this dorso-caudal level appears difficult to perform.

No. Fecal Boluses

before testing and again one hr following testing, after they had been allowed to drink again in their home cage. Results Analysis of variance showed no reliable differences among the groups in terms of shocks accepted (Fig. 2A) or intake of water after testing (Fig. 2B). Discussion Neither lesion of the dorsal fornix bundle nor the perforating fibers produced a passive avoidance deficit. Extensive bilateral hippocampal lesions produce passive avoidance deficit in the apparatus employed in the present study (Myhrer, unpublished observations). The results, therefore, may indicated that the dorsal fornix system is not significantly related to hippocampal structures affecting passive avoidance behavior. The occurrence of impaired passive avoidance following hippocampectomy is probably associated with both lesion size and the type of passive avoidance test used [34].

EXPERIMENT 2: PASSIVE AVOIDANCE Conflicting results have been obtained in passive avoidance tests after hippocampectomy. It has been suggested that investigators who used very small lesions failed to find a passive avoidance deficit, while those who used larger lesions did find a deficit (cf., [9]). However, large lesions are more likely to interrupt the dorsal fornix and the perforating fibers. Method A wooden box (50 x 52 x 23 cm), described elsewhere [28], was provided with a water dish wired to one terminal of a weak electric source. The other terminal was connected to a grid floor. Upon touching the water, the rat completed the circuit and received a relatively mild shock of about 0.35 mA. The rats were deprived of water for 48 hr and tested individually from Postoperative Day 20. Each rat was permitted to drink from the water dish for a total period of 2 rain. Then it was placed in the opposite corner of the apparatus; the water dish was electrified, and remained so for the 20 rain test period. The total n u m b e r of shocks accepted by the rat was recorded. In order to assess their motivational level the animals were weighed immediately

EXPERIMENT 3: HEBB-WILLIAMSMAZE LEARNING Several workers have shown impaired Hebb-Williams maze performance in hippocampectomized rats [19, 23, 27], but others have failed to reveal such an effect [14]. Hughes [19] has observed that antero-dorsal hippocampal lesions produced greater impairment than did posteroventral lesions. Since his antero-dorsal lesions were located near the midline, the dorsal fornix might have been damaged. Method The Hebb-Williams maze was the same as used for open field testing. For configurations of the 12 maze problems see Rabinovitch and Rosvold [30]. Since Problems 3 and 8 have low discrimination ability for both neocortical and hippocampal ablations [27], they were not used in the present study. From Postoperative Day 34 the rats only received water ½ hr following each training session; they had free access to food. The pretraining was carried out in 12 consecutive days. After having established an approach response to the goal box, the animals were run on the 6 pretraining problems, following which the actual testing begun. Animals

850

MYHRER AND K A A D A

200

A

150

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Y o o

4-

7

(/I

i

0 w

I00

hi

I

i

50

B 50

T

(/1

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I I

(.9

DF I (N7)

DFII (N7)

L Cont Norm (N7) (N7)

FIG. 3. Total number of errors committed in 10 Hebb-Williams maze problems in mean and -+ S. E. M.

I0

DF I (N8)

DFI[ (N8)

LCont (N8)

Norm (N9)

FIG. 2. Results of passive avoidance test. (A) Mean number of shock responses. (B) Increase of body weight in mean number of grams 1 hr after testing. Bars represent +_S. E. M. Abbreviations for this and following figures: L Cont = lesioned control; Norm = normal.

were run for 7 trials in each problem, one new problem each day for 10 consecutive days. Every trial was rewarded by some laps of water in the goal box. An animal was considered to have made an error if its two forepaws crossed an error line. Errors were recorded as the total number committed during 7 complete runs to the goal box; i.e., errors made after retracing from the goal box were not recorded.

Results Due to signs of possible labyrinthitis [5] five rats were excluded from the material: 1 animal from each of the experimental groups, 1 from the lesioned control group and 2 from the normal control group. Thus, henceforth all groups consisted of 7 animals. Both experimental groups exhibited impaired maze performance (Fig. 3). Analysis of variance of the total number of errors committed in 10 maze problems yielded a reliable treatment effect, F(3,24) = 9.9, p<0.01. Mean comparisons with two-tailed t test revealed that both experimental groups made significantly more errors than both control

groups (p<0.01). The DF-I group and the DF-II group did not differ reliably from each other; the lesioned control group and the normal control group likewise did not differ from each other. Figure 4 shows the mean number of errors for the groups for each type of problem used. It appears from this figure that the various problems possessed different discrimination abilities regarding the effect of dorsal fornix lesion. Learning curves based on total number of errors in all 10 problems as a function of trials, revealed intertrial improvement among all groups (Fig. 5). The experimental subjects learned as fast as the control animals, but they started out with a handicap already on the first trial (Fig. 5).

Discussion Transection of the dorsal fornix at both level I and II brought about impaired maze learning. Damage to the perforating fibers did not produce a reliable additional effect, although there was a tendency in this direction. However, the additional damage probably underlying the high level of open field activity among the DF-II animals might have masked a possible difference between dorsal fornix lesions at level I and II, even if increased open field activity in general does not necessarily result in a larger number of errors in Hebb-Williams maze [33]. This notion of masking effect is reconcilable with the fact that the dorsal fornix contains a far larger number of fibers at level I than at level II. The finding that antero-dorsal hippocampal lesions produce greater impairment than postero-ventral lesions in a Hebb-Williams maze [19], may be due to interruption of the dorsal fornix by the antero-dorsal lesions. Consequently, it is somewhat presumptive to suggest functional differentiation along the axial extent of the hippocampus on the

DORSAL FORNIX AND BEHAVIOR

851

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D F I (N7)

[~LConl'(NT)

[]

DFII

•

(N7)

Norm (N7)

n~ 15

o n- I0

6Jl

I.tl

5

I

I

:

7 PROBL

io

I

I=

I

iz

I

EMS

FIG. 4. Mean number of errors on each type of maze problem used.

40

-"

--" D F I ( N 7 )

=

-- D F I I ( N 7 )

e

=

L Cont(N7)

mso n.. o ty-

~2o I0 I I

I 2

I 3

I 4

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I 6

i 7

TRIALS FIG. 5. Learning curves based on mean number of errors on 10 maze problems. basis of data obtained with the usual ablation technique. Most lesions of a discrete structure are nearly always accompanied by additional damage, of varying extent, to surrounding tissue. The present results suggest that the dorsal fornix is involved in cognitive functions. However, the exact nature of its involvement is not yet understood. Dorsal fornixlesioned rats showed improved performance over 7 trials in the maze, indicating that their learning ability was not lost but only reduced. These experimental animals made more errors starting from the first trial (Fig. 5) when the problem was completely new. Their impaired performance in the maze may be interpreted as due to a short-term memory deficit, making it difficult for the rats to remember what parts of the maze they had already explored. However, since their open field and passive avoidance behavior were normal, this explanation seems somewhat implausible. Another related, and maybe more acceptable possibility, is a lesion-induced deficit in the processes of association. According to this interpretation, the change in test situation with presentation of each new maze problem was more distracting for the experimental subjects than for controls. The possibility of a long-term memory deficit in the experi-

mental rats appears untenable, since these animals showed during the pretraining in the maze situation that the previously acquired passive avoidance response was not extinguished. Alternative interpretations of the results should be considered. The impaired maze behavior is not likely attributable to a decrease in thirst drive, since the amount of water intake following the passive avoidance testing did not differ among the groups (Fig. 2B). Neither can emotional differences account for the results in view of the open field data, notably the defecation scores did not differentiate groups (Table 1). Normal performance in open field and passive avoidance tests appears to rule out the likelihood of sensory disturbances. However, a hypothesis of perseveration or repetition of body turns cannot be entirely excluded. As seen from Fig. 4 most maze problems were rather powerful in revealing the treatment effect. A similar configuration of the discrimination ability among the problems has also been shown after hippocampectomy [27]. However, in neither the latter study nor in the present one was a clear relationship found between the level of difficulty of the maze problems, as estimated by the performance of control animals, and the ability of the problems to distinguish between normal and brain-damaged rats. This finding may be explained by hypothesizing different rates of transfer of learning between experimental and control animals. EXPERIMENT 4: SPONTANEOUSALTERNATION Even if the D F - I animals of the present study did not show signs of perseveration in the open field and in the passive avoidance test, impaired maze performance may have been due to repetition of body turns. This hypothesis was investigated by measuring the rate of spontaneous alternation in a simple T-maze.

Method The testing was performed 60 days postoperatively in a s t a n d a r d unbaited T-maze (length of alleys 50 cm) previously described in detail [28]. The rat to be tested was placed in a start box and a sliding door to the main alley was opened after 5 sec. After traversing the maze and entering one of the goal boxes, the animal was placed on a table (60 x 120 cm) for 1 min before being returned to the

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MYHRER AND KAADA

start box for the next trial. Only 2 trials were given, and the choice of goal alley was recorded. Results The percentage of alternation among the groups was the following: DF-I, 57; DF-II, 57; lesioned control, 57; and normal, 71. Thus, no substantial differences occurred. Discussion Transection of the dorsal fornix did not affect spontaneous alternation behavior. The results imply that the maze deficit observed in the Hebb-Williams test was not due to repetition of body turns. The somewhat low level of alternation in all groups was likely related to the maze training. Even if the rats were very placid after prolonged handling in the maze learning situation, 1 1 of the 28 animals perseverated on the second trial, and in 8 instances the black goal box was chosen. The black alley was probably associated with reward, since the inserts making up the barriers in the Hebb-Williams maze were painted black as well. This finding indicates that the suggested association deficit among the experimental animals is rather slight and can only be revealed in situations like complex maze learning. GENERAL DISCUSSION The present study has shown that division of the dorsal fornix impaired Hebb-WiUiams problem solving, whereas damage to the fibers perforating the corpus callosum failed to yield reliable additional effect. Open field, passive avoidance and spontaneous alternation behavior remained unaffected by the target lesions of the dorsal fornix. As reported in the Introduction, the dorsal fornix has been supposed to contain a hippocampal output. If this is the case, some of the changes seen after CA1 damage may be expected to follow lesions of the dorsal fornix. Deefferentation of the hippocampal subfield CA1 at the subicular border results in increased open field activity [28], while section of the dorsal fornix does not produce this effect. This finding suggests that CA1 axons do not course in the dorsal fornix, and yields indirect support to the notion that the CA1 axons most likely terminate in the

subiculum [1,17]. Transection of the CA1 axons at the subicular border produces retrograde degeneration of the CA1 neurons [28], whereas corresponding degeneration was not observed in the present study. In further support of this view, fornicotomy [12, 22, 36, 39, 40, 411 fails to bring about the same behavioral changes observed after hippocampectomy (e.g., [9,24]). The output from the CA1 cells is likely unaffected by fornicotomy, although the CA3 output through the fimbria [4, 31, 32] is disrupted. In view of these considerations, the idea of subicular fiber contribution to the dorsal fornix is weakened. The behavioral changes seen after dorsal fornix sections have certain similarities with those occurring after neocortical lesions. Ablation of the neocortex overlying the dorsal hippocampus produces impaired Hebb-Williams maze learning, whereas open field, passive avoidance and spontaneous alternation behavior remains unaffected [28]. Even very slight cortical damage causes a Hebb-Williams maze deficit, with the cortical lesioned rats making more errors from the first trial [27]. Moreover, combined hippocampal an d c i n g u l a t e cortical damage appears to be more deleterious to maze performance than does injury to the hippocampus together with the cortex of dorsolateral aspects of the hemispheres [21]. Cingulate cortical lesions result in a pronounced loss in maze performance [38], whereas section of the cingulum bundle does not [37]. These findings, coupled with the previous considerations, indicate that the dorsal fornix fibers arise largely in the cingulate and retrosplenial cortex, as previously suggested to be the case for only a small portion of these fibers [6]. One may conclude that the dorsal fornix bundle is made up of fibers perforating the corpus callosum and not by axons from the hippocampus. The hypothesis that a slight association deficit results from dorsal fornix damage appears compatible with the assumption of neocortical origin of this fiber bundle. There is a close relationship between the dorsal fornix and the mamillary bodies [6, 7, 15, 32]. Removal of the latter results in defective maze learning in rats [21,38]. This is of interest, since damage to the mamillary bodies probably is related to Korsakoff psychosis in which disturban ces of memory are among the most conspicuous symptoms.

REFERENCES 1. Andersen, P., B. H. Bland and J. D. Dudar. Organization of the hippocampal output. Expl Brain Res. 17: 152-168, 1973. 2. Bender, R. M., G. Hostetter and G. J. Thomas. Effects of lesions in hippocampus-entorhinal cortex on maze performance and activity in rats. Psychon. Sei. 10: 13-14, 1968. 3. Bermant, G., S. E. Glickman and J. M. Davidson. Effects of limbic lesions on copulatory behavior of male rats. J. cornp. physiol. Psychol. 65: 118-125, 1968. 4. Cajal, S. RamSn y. Histologie du Systdme Nerveux de l'Homme et des Vertdbrds. T. 2, Paris: A. Maloine, 1911. 5. Cotchin. E. and F. J. C. Roe, Pathology o f Laboratory Rats and Mice. Oxford: Blackwell Scientific Publications, 1967, pp. 259-260. 6. Cragg, B. G. and L. H. Hamlyn. Histologic connections and electrical and autonomic responses evoked by stimulation of the dorsal fornix in the rabbit. Expl Neurol. 1: 187-213, 1959.

7. Cragg, B. G. and L. H. Hamlyn. Histological connections and visceral actions of components of the fimbria in the rabbit. ExplNeuroL 2: 581-597, 1960. 8. Daitz, H. M. and T. P. S. Powell. Studies of the connexions of the fornix system. J. Neurol. Neurosurg. Psychiat. 17: 75-82, 1954. 9. Douglas, R. J. The hippocampus and behavior. Psychol. Bull. 67: 416-442, 1967. 10. Eichelman, B. S. Jr. Effect of subcortical lesions on shockinduced aggression in the rat. J. comp. physiol. Psychol. 74: 331-339, 1971. 11. Elliot Smith, G. The 'fornix superior'. J. Anat. Physiol. 31: 80-94, 1897. 12. Fischman, M. and R. A. McCleary. Cited by McCleary, Response-modulating functions of the limbic system: Initiation and suppression. In: Progress in Physiological Psychology, Vol. 1, edited by E. Stellar and J. M. Sprague. New York: Academic Press, 1966, pp. 209-272.

DORSAL FORNIX AND BEHAVIOR 13. Ganser, S. Vergleichend-anatomische Studien tiber das Gehirn des Maulwurfs. MorphoL Jahrb. 7: 5 9 1 - 7 2 5 , 1882. 14. Gross, C. G., S. L. Chorover and S. M. Cohen. Caudate, cortical, hippocampal and dorsal thalamic lesions in rats: Alternation and Hebb-Williams maze performance. Neuropsychologia 3: 5 3 - 6 8 , 1965. 15. Guillery, R. W. Degeneration in the post-commissural fomix and mammillary peduncle of the rat. J. Anat. 90: 3 5 0 - 3 7 0 , 1956. 16. Hays, W. L. Statistics. New York: Holt, Rinehart and Winston, 1963, pp. 4 8 4 - 4 8 9 . 17. Hjorth-Simonsen, A. Some intrinsic connections of the hippocampus in the rat: An experimental analysis. J. comp. Neur. 147: 145-161, 1973. 18. Hostetter, G. and G. J. Thomas. Evaluation of enhanced thigmotaxis as a condition of impaired maze learning by rats with hippocampal lesions. J. comp. physiol. Psychol. 63: 105-110, 1967. 19. Hughes, K. R. Dorsal and ventral hippocampus lesions and maze learning: influence of preoperative environment. Can. J. Psychol. 19: 3 2 5 - 3 3 2 , 1965. 20. Jarrard, L. E. Behavior of hippocampal lesioned rats in home cage and novel situations. Physiol. Behav. 3: 6 5 - 7 0 , 1968. 21. Kaada, B. R., E. W. Rasmussen and O. Kveim. Effects ofhippocampal lesions on maze learning and retention in rats. Expl Neurol. 3: 3 3 3 - 3 5 5 , 1961. 22. Kaada, B. R., E. W. Rasmussen and O. Kveim. Impaired acquisition of passive avoidance behavior by subcallosal, septal, hypothalamic and insular lesions in rats. J. comp. physiol. Psychol. 55: 6 6 1 - 6 7 0 , 1962. 23. Kimble, D. P. The effects of bilateral hippocampal lesions in rats. J. comp. physioL Psychol. 56: 2 7 3 - 2 8 3 , 1963. 24. Kimble, D. P. Hippoeampus and internal inhibition. Psychol. Bull. 70: 2 8 5 - 2 9 5 , 1968. 25. Kirkby, R. J., D. G. Stein, R. J. Kimble and D. P. Kimble. Effects of hippocampal lesions and duration of sensory input on spontaneous alternation. J. comp. physiol. Psychol. 64: 3 4 2 - 3 4 5 , 1967. 26. Koelliker, A. Handbuch der Gewebelehre des Menschen, Bd. 2, 6. Aufl. Leipzig: Engelmann, 1896, pp. 7 7 9 - 7 8 8 . 27. Kveim, O., J. Setekleiv and B. R. Kaada. Differential effects of hippocampal lesions on maze and passive avoidance learning in rats. ExplNeurol. 9: 5 9 - 7 2 , 1964.

853 28. Myhrer, T. Locomotor, avoidance and maze behavior in rats with selective disruption of hippocampal output. J. comp. physiol. Psyehol. in press. 29. Powell, T. P. S. and W. M. Cowan. An experimental study of the efferent connexions of the hippocampus. Brain 78: 115-132, 1955. 30. Rabinovitch, M. S. and H. E. Rosvold. A closed-field intelligence test for rats. Can. Z Psychol. 5: 122-128, 1951. 31. Raisman, G. The connections of the septum. Brain 89: 3 1 7 - 3 4 8 , 1966. 32. Raisman, G., W. M. Cowan and T. P. S. Powell. An experimental analysis of the efferent projection of the hippocampus. Brain 89: 8 3 - 1 0 8 , 1966. 33. Smith, H. V. Effects of environmental enrichment on openfield activity and Hebb-Williams problem solving in rats. J. comp. physiol. Psychol. 80: 163-168, 1972. 34. Snyder, D. R. and R. L. Isaacson. Effects of large and small bilateral hippocampal lesions on two types of passive avoidance responses. Psychol. Rep. 16: 1277-1290, 1965. 35. Strong, P. N. Jr. and W. J. Jackson. Effects of hippocampal lesions in rats on three measures of activity. Z comp. physiol. Psychol. 70: 6 0 - 6 5 , 1970. 36. Thomas, G. J. Maze retention by rats with hippocampal lesions and fornicotomies. J. comp. physiol. Psychol. 75: 4 1 - 4 9 , 1971. 37. Thomas, G. J. and B. Slotnick. Effects of lesions in the cingulum on maze learning and avoidance conditioning in the rat. J. comp. physiol. Psychol. 55: 1085-1091, 1962. 38. Thompson, R. Localization of the "maze memory system" in the white rat. Physiol. Psychol. 2: 1 - 1 7 , 1974. 39. Van Hoesen, G. W., J. M. MacDougall and J. C. Mitchell. Anatomical specificity of septal projections in active and passive avoidance behavior in rats. J. comp. physiol. Psychol. 68: 8 0 - 8 9 , 1969. 40. Van Hoesen, G. W., L. M: Wilson, J. M. MacDougaU and J. C. Mitchell. Selective hippocampal complex deafferentation and deefferentation and avoidance behavior in rats. Physiol. Behav. 8: 8 7 3 - 8 7 9 , 1972. 41. Woody, C. D. and F. R. Erwin. Memory function in cats with lesions of the fornix and mammillary bodies. Physiol. Behav. 1: 273-280, 1966.