- Email: [email protected]
Spatial memory impairment in ventral subicular lesioned rats
Brain Research 816 Ž1999. 245–248
Short communication
Spatial memory impairment in ventral subicular lesioned rats T.R. Laxmi, P.N. Bindu, T.R. Raju, B.L. Meti
)
Department of Neurophysiology, National Institute of Mental Health and Neurosciences, P.B. 2900, Hosur Road, Bangalore-560 029, Karnataka, India Accepted 27 October 1998
Abstract The present study examined the effects of ibotenic acid lesions of the ventral subiculum ŽSUB. on the ability of rats to memorize a rewarded alternation test in a T-maze. Results indicated that rats with ibotenic acid lesions ŽIL. of the ventral subiculum were impaired in postoperative acquisition of the spatial discrimination task, making more errors than the vehicle treated and normal control rats. In addition, all rats, including the IL group of rats, were able to memorize an acquired spatial behaviour. These findings suggest that the SUB play an important role in spatial information processing in rats. q 1999 Elsevier Science B.V. All rights reserved. Keywords: Ventral subiculum; Ibotenic acid; T-maze; Rewarded alternation task
Subiculum, an area of the hippocampal formation, is considered to constitute the major output structure of the hippocampus and sends their projections to various subcortical and neocortical regions w7,17,18x. The experimental evidence suggests that the subiculum has both afferent and efferent connections with hippocampus, entorhinal cortex, medial septum, nucleus accumbens and amygdala w14x. The earlier studies on subiculum showed its involvement in the working memory. The lesioning of this area by electrolyticrchemical means caused an impairment in acquisition of operant behaviour and the reduction in the number of neurons in CA1 area of the hippocampus w4,9x. The ibotenic acid lesioning of the subiculum and entorhinal cortex ŽEC. showed an impairment in eight-arm radial maze tasks w2x. Similarly, the lesions of the retrohippocampal area, including the subicular complex and EC, lead to impaired performance on the Morris water maze task w8,13x. The electrophysiological data have shown that cells in the subiculum fired in both location- and directionspecific manner w14x. This report is consistent with the concept that the role of the subiculum is as part of the neural network involved in spatial information processing. All these data support the idea that the EC and subiculum might, either in concert with the hippocampus or as separate functional units, mediate spatial memory representa-
) Corresponding author. [email protected]
Fax:
q 91-080-663830;
Em ail:
tion into the higher cortical regions. But to date, no reports are available to indicate the role of the ventral subiculum in spatial learning using T-maze paradigm. The present study was, thus, aimed at determining whether selective lesions of the ventral subiculum using ibotenic acid in rats disrupts the postoperative acquisition of a spatial learning Žrewarded alternation task. in a T-maze. Young male Wistar rats, housed separately under a 12-h dark–light cycle with food and water available ad libitum, were used. The rats were divided into: normal control ŽNC., sham control ŽSC. and ibotenic acid lesioned ŽIL. having six animals in each group.The behavioural study was carried out in two sets of experiments.In the first set, the ventral subiculum was lesioned in naive 30-day-old rats and exposed for the spatial learning test in T-maze. While in the second set, the rats were lesioned after learning the spatial task and then exposed them for the retention test. The lesioning was performed under ketamine anaesthesia by injecting ibotenic acid into the ventral subiculum at multiple sites with the help of a microinjector Ž0.05 mlrmin, 0.25 mlrsite. at two different sites using modified coordinates adapted from Paxinos and Watson w12x ŽAP s y6.0 mm; ML s 4.0 to 4.5 mm; and DV s 7.0 mm. stereotaxic atlas. Seven days after the surgery, the first set of rats were trained for the rewarded alternation test wherein the rats were placed in T-maze w21x. Initially, the rats were kept in T-maze to familiarise with the environment. For the orientation session, the reward Žfood pellet. was placed alter-
0006-8993r99r$ - see front matter q 1999 Elsevier Science B.V. All rights reserved. PII: S 0 0 0 6 - 8 9 9 3 Ž 9 8 . 0 1 1 8 7 - 1
246
T.R. Laxmi et al.r Brain Research 816 (1999) 245–248
nately in goal area of the maze and allowed the rats to eat food pellets. These rats were then subjected to 10 trials per session until they reach the criterion of nine correct choices. In the second set of experiments, the rats were trained for the rewarded alternation test. After the completion of the spatial task, these rats were divided into three groups: one group Ž n s 6. was subjected for bilateral ventral subicular lesion ŽIL.; the second group Ž n s 6. was sham control and the third group Ž n s 6. did not undergo any surgery. These rats were then exposed for one more experimental session after the seven days of postsurgical recovery to check the retention of the acquired behaviour. All the rats tested this way were active and no immobility was observed. Following completion of the behavioural experiments, the rats were perfused transcardially under deep anaesthesia with a formyl saline solution for the histological verification of electrode placement sites and the extent of subicular damage by ibotenic acid, using cresyl-violet staining ŽFig. 1.. Data were analysed for statistical significance by means of two-factor Žtreatmentrsession. analysis of variance with repeated measures on one-factor Žsession.
followed by Newman Keul’s post-hoc test and one-way ANOVA w15x. In the first set of experiments, the ventral subicular lesioned rats showed an impairment in the acquisition of rewarded alternation test. They were unable to attain the criterion Žnine correct choices out of 10 trials. even in seven sessions, though the control rats reached the criterion in three to five sessions Ž p - 0.001, Fig. 2..The statistical analysis revealed a significant effect on treatment Ž F2,15 s 58.47, p - 0.001., time Ž F6,90 s 7.15, p 0.01. as well as on the interaction Ž F2,90 s 3.90, p - 0.01. ŽFig. 2.. In the second set of experiments, the retention of spatial learning was assessed and it was found that subicular lesioned rats could retain the acquired spatial behaviour. Their performance in the retention trials was similar to that of normal and sham control rats. Hence the results indicate that the bilateral subicular lesions cause an impairment in the acquisition, but not the retention of the spatial tasks. The morphological studies from our laboratory indicated that the electrolyticrchemical lesioning of ventral
Fig. 1. Schematic representation of the extent of damage of ventral subiculum in ibotenic acid lesioned rats. Shaded areas indicates cell damage in different planes from bregma y5.8 to 7.3 mm, corresponding to the Paxinos and Watson rat atlas.
T.R. Laxmi et al.r Brain Research 816 (1999) 245–248
Fig. 2. Mean number of alternations in rats during acquisition of rewarded alternation test in T-maze. Each point on the graph represents the mean ŽqS.D.. data from six rats in a group. Note a significantly Ž) p- 0.001. less number of alternations performed in IL group of rats from 4th to 7th sessions.
247
an eight-arm radial maze. Also, the ibotenic acid lesioning of the ventral subiculum alone was reported to produce an impairment in the pedal press rate of operant behaviour w4x. Interestingly, the present study revealed that the ventral subicular lesion by ibotenic acid caused an impairment in the acquisition of spatial task, rewarded alternation test, but not the retention. It is important to note that the rats with selective lesions of the subiculum were not able to learn the rewarded alternation task but were normal in acquiring stored spatial information. Apparently, the normal retention may be possible because animals can use an alternative strategy that involves the learning to approach the correct area of the maze using the neocortical regions w16x, whereas the impairment in acquiring new information may be due to the selective damage in these areas, which may participate in the transferring the processed hippocampal information to the neocortex. In conclusion, the present study suggests that the subiculum is found to be an important area for spatial information coding and processing during the early stages of learning in rats.
References subiculum in young rats led to substantial cell shrinkage in CA1 pyramidal cells w4x and a significant reduction in dendritic branching and intersection points of apical and basal dendrites of CA1 and CA3 neurons w9x. Various behavioral studies suggest that the different kinds of lesions of hippocampus along with related structures invariably cause an impairment in long-term spatial memories w1,5,6,8,10,11x. Similarly, the study includes the bilateral lesions of the fimbria-fornix or EC produced a severe impairment in the ability of the rat to choose the goal accurately in a radial arm maze task w1,10,11x. Subsequent research showed that the selective ibotenic acid lesions of the CA1 cell field were found to produce an impairment in the acquisition of complex place and cue tasks in rats w8x. Volpe et al. w20x correlated the selective loss of hippocampal CA1 pyramidal neurons produced due to ischemia or neurotoxicity with the memory impairments in rats. Therefore, the CA1 pyramidal neurons play a crucial role in learning and memory and the loss of these neurons may cause severe impairments in various tasks. In addition, bilateral electrolytic or neurotoxic lesions of the postsubiculum produced an impairment in eight-arm radial maze task and a Morris water maze task, although the performance scores of both lesioned groups improved over the course of behaviour testing w19x. Goodlett et al. w3x reported that the lesioning of the entire retrohippocampal area, including subicular complex and EC caused an impairment in a T-maze task, whereas Cho and Jaffard w2x have reported that the discrete and selective ibotenic acid lesions of the entorhinal cortex or subiculum impairs the animal’s capacity to memorize a single spatial location in
w1x J.B. Brierley, Neuropathology of amnesic states, in: C.W.M. Witty, O.L. Zangwill ŽEds.., Amnesia, 2nd edn., Butterworth, London, 1997, pp. 199–223. w2x Y.H. Cho, R. Jaffard, Spatial location learning in mice with ibotenate lesions of entorhinal cortex or subiculum, Neurobiol. Learn. Mem. 64 Ž1995. 285–290. w3x C.R. Goodlett, J.M. Nichols, R.W. Halloran, J.R. West, Long-term deficits in water maze spatial conditional alternation performance following retrohippocampal lesions in rats, Behav. Brain Res. 32 Ž1989. 63–67. w4x Govindaiah, B.S.S. Rao, T.R. Raju, B.L. Meti, Loss of hippocampal CA1 neurons and learning impairment in subicular lesioned rats, Brain Res. 745 Ž1997. 121–126. w5x L.E. Jarrard, H. Okaichi, R. Gold Schmidt, O. Steward, On the role of hippocampal connections in the performance of place and cue tasks: comparison with damage to hippocampus, Behav. Neurosci. 98 Ž1984. 946–954. w6x L.E. Jarrard, Selective hippocampal lesions: differential effects on performance by rats of spatial tasks with pre-operative and post-operative training, J. Comp. Physiol. Psychol. 92 Ž1978. 1119–1127. w7x F.H. Lopes da Silva, M.P. Witter, P.H. Boeijinga, A.H.M. Lohman, Anatomic organization and physiology of the limbic cortex, Physiol. Rev. 70 Ž1990. 453–511. w8x R.G.M. Morris, F. Schenk, F. Tweedie, L.E. Jarrard, Ibotenate lesions of hippocampus andror subiculum: dissociating components of allocentric spatial learning, Eur. J. Neurosci. 2 Ž1990. 1016–1028. w9x W.D. Nutan, B.L. Meti, Effects of subicular lesions on operant behaviour and dendritic arborizations of CA1, CA3 hippocampal neurons, Neurol. India 44 Ž4. Ž1996. 14, Abstr. w10x D.S. Olton, J.J. Becker, G.E. Handelman, Hippocampus, space and memory, Behav. Brain Sci. 2 Ž1979. 313–322. w11x D.S. Olton, J.A. Walker, F.H. Gage, Hippocampal connections and spatial discrimination, Brain Res. 139 Ž1978. 295–308. w12x G. Paxinos, C. Watson, The Rat Brain in Stereotaxic Coordinates, Academic Press, Sydney, 1986. w13x F. Schenk, R.G.M. Morris, Dissociation between components of
248
w14x
w15x w16x
w17x w18x
T.R. Laxmi et al.r Brain Research 816 (1999) 245–248 spatial memory in rats after recovery from the hippocampal lesions, Exp. Brain Res. 58 Ž1985. 11–28. P.E. Sharp, J.B. Ranck Jr., R.U. Muller, Direction and location correlates of cell firing in the rat subiculum, Soc. Neurosci. Abstr. 16 Ž1990. 737. G.W. Snedecor, W.G. Cochran, Statistical Methods, Oxford and IBH Publications, New Delhi, 1967. R.J. Sutherland, I.Q. Whishaw, B. Kolb, Contribution of cingulate cortex to two forms of spatial learning and memory, J. Neurosci. 8 Ž1988. 1863–1872. L.W. Swanson, W.M. Cowan, The connections of the septal region in the rat, J. Comp. Neurol. 186 Ž1979. 621–656. L.W. Swanson, W.M. Cowan, An autoradiographic study of the
organization of the efferent connections of the hippocampal formation in rat, J. Comp. Neurol. 172 Ž1997. 49–84. w19x J.S. Taube, J.P. Kesslak, C.W. Cotman, Lesions of the rat postsubiculum impair performance on spatial tasks, Behav. Neural Biol. 57 Ž1992. 131–143. w20x B.T. Volpe, A. Towle, W.P. Dunlop, Loss of hippocampal CA1 pyramidal neurons correlates with memory impairment in rats with ischemic or neurotoxic lesions, Behav. Neurosci. 106 Ž1992. 457– 464. w21x D. Yoganarasimha, B.S.S. Rao, T.R. Raju, B.L. Meti, Facilitation of acquisition and performance of operant and spatial learning tasks in self-stimulation experienced rats, Behav. Neurosci. 112 Ž1998. 725– 729.
Short communication
Spatial memory impairment in ventral subicular lesioned rats T.R. Laxmi, P.N. Bindu, T.R. Raju, B.L. Meti
)
Department of Neurophysiology, National Institute of Mental Health and Neurosciences, P.B. 2900, Hosur Road, Bangalore-560 029, Karnataka, India Accepted 27 October 1998
Abstract The present study examined the effects of ibotenic acid lesions of the ventral subiculum ŽSUB. on the ability of rats to memorize a rewarded alternation test in a T-maze. Results indicated that rats with ibotenic acid lesions ŽIL. of the ventral subiculum were impaired in postoperative acquisition of the spatial discrimination task, making more errors than the vehicle treated and normal control rats. In addition, all rats, including the IL group of rats, were able to memorize an acquired spatial behaviour. These findings suggest that the SUB play an important role in spatial information processing in rats. q 1999 Elsevier Science B.V. All rights reserved. Keywords: Ventral subiculum; Ibotenic acid; T-maze; Rewarded alternation task
Subiculum, an area of the hippocampal formation, is considered to constitute the major output structure of the hippocampus and sends their projections to various subcortical and neocortical regions w7,17,18x. The experimental evidence suggests that the subiculum has both afferent and efferent connections with hippocampus, entorhinal cortex, medial septum, nucleus accumbens and amygdala w14x. The earlier studies on subiculum showed its involvement in the working memory. The lesioning of this area by electrolyticrchemical means caused an impairment in acquisition of operant behaviour and the reduction in the number of neurons in CA1 area of the hippocampus w4,9x. The ibotenic acid lesioning of the subiculum and entorhinal cortex ŽEC. showed an impairment in eight-arm radial maze tasks w2x. Similarly, the lesions of the retrohippocampal area, including the subicular complex and EC, lead to impaired performance on the Morris water maze task w8,13x. The electrophysiological data have shown that cells in the subiculum fired in both location- and directionspecific manner w14x. This report is consistent with the concept that the role of the subiculum is as part of the neural network involved in spatial information processing. All these data support the idea that the EC and subiculum might, either in concert with the hippocampus or as separate functional units, mediate spatial memory representa-
) Corresponding author. [email protected]
Fax:
q 91-080-663830;
Em ail:
tion into the higher cortical regions. But to date, no reports are available to indicate the role of the ventral subiculum in spatial learning using T-maze paradigm. The present study was, thus, aimed at determining whether selective lesions of the ventral subiculum using ibotenic acid in rats disrupts the postoperative acquisition of a spatial learning Žrewarded alternation task. in a T-maze. Young male Wistar rats, housed separately under a 12-h dark–light cycle with food and water available ad libitum, were used. The rats were divided into: normal control ŽNC., sham control ŽSC. and ibotenic acid lesioned ŽIL. having six animals in each group.The behavioural study was carried out in two sets of experiments.In the first set, the ventral subiculum was lesioned in naive 30-day-old rats and exposed for the spatial learning test in T-maze. While in the second set, the rats were lesioned after learning the spatial task and then exposed them for the retention test. The lesioning was performed under ketamine anaesthesia by injecting ibotenic acid into the ventral subiculum at multiple sites with the help of a microinjector Ž0.05 mlrmin, 0.25 mlrsite. at two different sites using modified coordinates adapted from Paxinos and Watson w12x ŽAP s y6.0 mm; ML s 4.0 to 4.5 mm; and DV s 7.0 mm. stereotaxic atlas. Seven days after the surgery, the first set of rats were trained for the rewarded alternation test wherein the rats were placed in T-maze w21x. Initially, the rats were kept in T-maze to familiarise with the environment. For the orientation session, the reward Žfood pellet. was placed alter-
0006-8993r99r$ - see front matter q 1999 Elsevier Science B.V. All rights reserved. PII: S 0 0 0 6 - 8 9 9 3 Ž 9 8 . 0 1 1 8 7 - 1
246
T.R. Laxmi et al.r Brain Research 816 (1999) 245–248
nately in goal area of the maze and allowed the rats to eat food pellets. These rats were then subjected to 10 trials per session until they reach the criterion of nine correct choices. In the second set of experiments, the rats were trained for the rewarded alternation test. After the completion of the spatial task, these rats were divided into three groups: one group Ž n s 6. was subjected for bilateral ventral subicular lesion ŽIL.; the second group Ž n s 6. was sham control and the third group Ž n s 6. did not undergo any surgery. These rats were then exposed for one more experimental session after the seven days of postsurgical recovery to check the retention of the acquired behaviour. All the rats tested this way were active and no immobility was observed. Following completion of the behavioural experiments, the rats were perfused transcardially under deep anaesthesia with a formyl saline solution for the histological verification of electrode placement sites and the extent of subicular damage by ibotenic acid, using cresyl-violet staining ŽFig. 1.. Data were analysed for statistical significance by means of two-factor Žtreatmentrsession. analysis of variance with repeated measures on one-factor Žsession.
followed by Newman Keul’s post-hoc test and one-way ANOVA w15x. In the first set of experiments, the ventral subicular lesioned rats showed an impairment in the acquisition of rewarded alternation test. They were unable to attain the criterion Žnine correct choices out of 10 trials. even in seven sessions, though the control rats reached the criterion in three to five sessions Ž p - 0.001, Fig. 2..The statistical analysis revealed a significant effect on treatment Ž F2,15 s 58.47, p - 0.001., time Ž F6,90 s 7.15, p 0.01. as well as on the interaction Ž F2,90 s 3.90, p - 0.01. ŽFig. 2.. In the second set of experiments, the retention of spatial learning was assessed and it was found that subicular lesioned rats could retain the acquired spatial behaviour. Their performance in the retention trials was similar to that of normal and sham control rats. Hence the results indicate that the bilateral subicular lesions cause an impairment in the acquisition, but not the retention of the spatial tasks. The morphological studies from our laboratory indicated that the electrolyticrchemical lesioning of ventral
Fig. 1. Schematic representation of the extent of damage of ventral subiculum in ibotenic acid lesioned rats. Shaded areas indicates cell damage in different planes from bregma y5.8 to 7.3 mm, corresponding to the Paxinos and Watson rat atlas.
T.R. Laxmi et al.r Brain Research 816 (1999) 245–248
Fig. 2. Mean number of alternations in rats during acquisition of rewarded alternation test in T-maze. Each point on the graph represents the mean ŽqS.D.. data from six rats in a group. Note a significantly Ž) p- 0.001. less number of alternations performed in IL group of rats from 4th to 7th sessions.
247
an eight-arm radial maze. Also, the ibotenic acid lesioning of the ventral subiculum alone was reported to produce an impairment in the pedal press rate of operant behaviour w4x. Interestingly, the present study revealed that the ventral subicular lesion by ibotenic acid caused an impairment in the acquisition of spatial task, rewarded alternation test, but not the retention. It is important to note that the rats with selective lesions of the subiculum were not able to learn the rewarded alternation task but were normal in acquiring stored spatial information. Apparently, the normal retention may be possible because animals can use an alternative strategy that involves the learning to approach the correct area of the maze using the neocortical regions w16x, whereas the impairment in acquiring new information may be due to the selective damage in these areas, which may participate in the transferring the processed hippocampal information to the neocortex. In conclusion, the present study suggests that the subiculum is found to be an important area for spatial information coding and processing during the early stages of learning in rats.
References subiculum in young rats led to substantial cell shrinkage in CA1 pyramidal cells w4x and a significant reduction in dendritic branching and intersection points of apical and basal dendrites of CA1 and CA3 neurons w9x. Various behavioral studies suggest that the different kinds of lesions of hippocampus along with related structures invariably cause an impairment in long-term spatial memories w1,5,6,8,10,11x. Similarly, the study includes the bilateral lesions of the fimbria-fornix or EC produced a severe impairment in the ability of the rat to choose the goal accurately in a radial arm maze task w1,10,11x. Subsequent research showed that the selective ibotenic acid lesions of the CA1 cell field were found to produce an impairment in the acquisition of complex place and cue tasks in rats w8x. Volpe et al. w20x correlated the selective loss of hippocampal CA1 pyramidal neurons produced due to ischemia or neurotoxicity with the memory impairments in rats. Therefore, the CA1 pyramidal neurons play a crucial role in learning and memory and the loss of these neurons may cause severe impairments in various tasks. In addition, bilateral electrolytic or neurotoxic lesions of the postsubiculum produced an impairment in eight-arm radial maze task and a Morris water maze task, although the performance scores of both lesioned groups improved over the course of behaviour testing w19x. Goodlett et al. w3x reported that the lesioning of the entire retrohippocampal area, including subicular complex and EC caused an impairment in a T-maze task, whereas Cho and Jaffard w2x have reported that the discrete and selective ibotenic acid lesions of the entorhinal cortex or subiculum impairs the animal’s capacity to memorize a single spatial location in
w1x J.B. Brierley, Neuropathology of amnesic states, in: C.W.M. Witty, O.L. Zangwill ŽEds.., Amnesia, 2nd edn., Butterworth, London, 1997, pp. 199–223. w2x Y.H. Cho, R. Jaffard, Spatial location learning in mice with ibotenate lesions of entorhinal cortex or subiculum, Neurobiol. Learn. Mem. 64 Ž1995. 285–290. w3x C.R. Goodlett, J.M. Nichols, R.W. Halloran, J.R. West, Long-term deficits in water maze spatial conditional alternation performance following retrohippocampal lesions in rats, Behav. Brain Res. 32 Ž1989. 63–67. w4x Govindaiah, B.S.S. Rao, T.R. Raju, B.L. Meti, Loss of hippocampal CA1 neurons and learning impairment in subicular lesioned rats, Brain Res. 745 Ž1997. 121–126. w5x L.E. Jarrard, H. Okaichi, R. Gold Schmidt, O. Steward, On the role of hippocampal connections in the performance of place and cue tasks: comparison with damage to hippocampus, Behav. Neurosci. 98 Ž1984. 946–954. w6x L.E. Jarrard, Selective hippocampal lesions: differential effects on performance by rats of spatial tasks with pre-operative and post-operative training, J. Comp. Physiol. Psychol. 92 Ž1978. 1119–1127. w7x F.H. Lopes da Silva, M.P. Witter, P.H. Boeijinga, A.H.M. Lohman, Anatomic organization and physiology of the limbic cortex, Physiol. Rev. 70 Ž1990. 453–511. w8x R.G.M. Morris, F. Schenk, F. Tweedie, L.E. Jarrard, Ibotenate lesions of hippocampus andror subiculum: dissociating components of allocentric spatial learning, Eur. J. Neurosci. 2 Ž1990. 1016–1028. w9x W.D. Nutan, B.L. Meti, Effects of subicular lesions on operant behaviour and dendritic arborizations of CA1, CA3 hippocampal neurons, Neurol. India 44 Ž4. Ž1996. 14, Abstr. w10x D.S. Olton, J.J. Becker, G.E. Handelman, Hippocampus, space and memory, Behav. Brain Sci. 2 Ž1979. 313–322. w11x D.S. Olton, J.A. Walker, F.H. Gage, Hippocampal connections and spatial discrimination, Brain Res. 139 Ž1978. 295–308. w12x G. Paxinos, C. Watson, The Rat Brain in Stereotaxic Coordinates, Academic Press, Sydney, 1986. w13x F. Schenk, R.G.M. Morris, Dissociation between components of
248
w14x
w15x w16x
w17x w18x
T.R. Laxmi et al.r Brain Research 816 (1999) 245–248 spatial memory in rats after recovery from the hippocampal lesions, Exp. Brain Res. 58 Ž1985. 11–28. P.E. Sharp, J.B. Ranck Jr., R.U. Muller, Direction and location correlates of cell firing in the rat subiculum, Soc. Neurosci. Abstr. 16 Ž1990. 737. G.W. Snedecor, W.G. Cochran, Statistical Methods, Oxford and IBH Publications, New Delhi, 1967. R.J. Sutherland, I.Q. Whishaw, B. Kolb, Contribution of cingulate cortex to two forms of spatial learning and memory, J. Neurosci. 8 Ž1988. 1863–1872. L.W. Swanson, W.M. Cowan, The connections of the septal region in the rat, J. Comp. Neurol. 186 Ž1979. 621–656. L.W. Swanson, W.M. Cowan, An autoradiographic study of the
organization of the efferent connections of the hippocampal formation in rat, J. Comp. Neurol. 172 Ž1997. 49–84. w19x J.S. Taube, J.P. Kesslak, C.W. Cotman, Lesions of the rat postsubiculum impair performance on spatial tasks, Behav. Neural Biol. 57 Ž1992. 131–143. w20x B.T. Volpe, A. Towle, W.P. Dunlop, Loss of hippocampal CA1 pyramidal neurons correlates with memory impairment in rats with ischemic or neurotoxic lesions, Behav. Neurosci. 106 Ž1992. 457– 464. w21x D. Yoganarasimha, B.S.S. Rao, T.R. Raju, B.L. Meti, Facilitation of acquisition and performance of operant and spatial learning tasks in self-stimulation experienced rats, Behav. Neurosci. 112 Ž1998. 725– 729.