Behavioural Brain Research 133 (2002) 279 /291

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Research report

Hippocampal lesioned rats are able to learn a spatial position using

non-spatial strategies
Bruno Pouzet a,1, Wei-Ning Zhang a, Joram Feldon a,*, J. Nicholas P. Rawlins b
a
Behavioral Neurobiology Laboratory, Swiss Federal Institute of Technology, Schorenstrasse 16, CH 8603 Schwerzenbach, Switzerland
b
Department of Experimental Psychology, University of Oxford, South Parks Road, Oxford OX1 3UD, UK

Received 10 August 2001; received in revised form 2 January 2002; accepted 2 January 2002

Abstract

In the last two decades, many experiments have demonstrated that the hippocampus plays a role in the learning and processing of
spatial and contextual information. Despite these demonstrations, some recent publications have indicated that the hippocampus is
not the only structure involved in spatial learning and that even after hippocampal lesions, rats can perform spatial tasks. However,
it is not well established whether animals with hippocampal dysfunction still have some spatial learning capacities or develop non-
spatial solutions; these may require lengthier acquisition training. We now report the effects of conventional, dorsal hippocampal
ablation on rats’ performance on the water maze. We tested rats using a short (4 days) versus a long (16 days) acquisition period. We
demonstrated that animals with dorsal hippocampal lesions have some residual capacity for learning the localization of a hidden
escape platform in a pool during both a reference memory task and a working memory task. The animals with dorsal hippocampal
lesions learned to escape at a fixed location, but only with extended training. It is suggested that these animals used non-spatial
strategies to compensate for a spatial memory impairment. The results are discussed with respect to the experimental procedure and
the strategy applied by the lesioned rats. # 2002 Elsevier Science B.V. All rights reserved.

Keywords: Hippocampus; Spatial learning; Morris water maze; Lesion

1. Introduction handling (even complex) non-spatial information

Since the studies of Scoville and Milner in 1957 [44], it
has been demonstrated by several investigators in
humans that, under some task conditions, damage to
the hippocampal formation results in severe memory
impairment, affecting non-spatial learning processes
[11], or spatial learning processes [22,45,46,57] (but see
[40,56]). In parallel, two decades of animal research have
aimed at creating experimental models of the memory
dysfunctions observed in humans. The general finding
that rats without a hippocampus are impaired on tasks
that require the utilization of spatial [4] and contextual
information [17,20,35], stands in contrast to the spared
performance that has been found in learning about and
* Corresponding author. Tel.:
41-1-655-7448; fax:
41-1-655-
7203
E-mail address: feldon@toxi.biol.ethz.ch (J. Feldon).
1
Present address: H. Lundbeck A/S, Ottilia vej 7/9,
Psychopharmacology Psychosis, DK 2500 Valby, Denmark.
0166-4328/02/$ - see front matter # 2002 Elsevier Science B.V. All rights reserved.
PII: S 0 1 6 6 - 4 3 2 8 ( 0 2 ) 0 0 0 0 7 - 4
[1,8,14], although this spared capacity is subject to
discussion [41,66]. Other structures anatomically related
to the hippocampus, such as the dorsal striatum [21], the
subiculum [26], subcortical structures [51,64] or the
parietal [42] and entorhinal cortex [43] have also been
implicated in the spatial memory capacities of animals
or humans [36,47]. Consequently, there have been many
attempts to establish models of memory impairments in
hippocampectomized animals, but the results have been
variable, depending on both the experimental paradigms
used and the precise location of the lesion, i.e. in the
hippocampus, or more generally in the hippocampal
formation, the definition of which is also variable [2]. In
the 1980s, Morris [23,25] designed the water maze task
that has been used in hundreds of studies with rodents,
many of which led to the claim that the hippocampus,
perhaps disproportionately, is the substrate of learning
and more precisely of spatial learning [29,31,55]. This
conclusion was based on the observation that in the
water maze, normal rats quickly acquire a place naviga-
280 B. Pouzet et al. / Behavioural Brain Research 133 (2002) 279 /291
tion response when required to find and to learn about
the location of a hidden escape platform in a swimming
pool [23], whereas rats with hippocampal dysfunction
induced by hippocampal lesions [25,54] or fimbria /
fornix lesions [51] are severely impaired on this task.
Current positions regarding hippocampal involvement
in learning and memory differ primarily in proposing
either that the hippocampus is involved in the processing
of and memory for one type of information, specifically,
spatial information [29,31,32,65] or that the structure is
more involved in particular learning and/or memory
processes that are non-specific for information type, e.g.
declarative memory [7,10,48,49], working memory [5],
temporary memory [39], and configural learning [52].
Despite attempts to integrate these theories [15], the
precise involvement of the hippocampus, and the stage
of memory processing at which the hippocampus plays a
role, remain unclear. In addition, it has been suggested
that rats use two different strategies to handle spatial
information, i.e. an idiocentric strategy, based on the
subject’s body position in space, and an allocentric
strategy, which is independent of the subject’s body
position in space [19,58]. Recently, Whishaw and cow-
orkers demonstrated that rats with hippocampal lesions
have more difficulty in deriving and using an appro-
priate strategy to reach a defined location in space than
in learning about a spatial location [63]. Moreover, the
same author using a non-water maze task suggested that
the hippocampal formation of rats might be involved
not in spatial mapping itself, but instead in the move-
ments required for exploration and in the integration of
these movements to permit mapping [59,61]. Thus,
determining the involvement and the precise role of
the hippocampus in spatial memory processing appears
to be difficult and requires specific lesions to be
combined with careful behavioral analyses in precise
paradigms. The learning of spatial cues during a test is
expected to occur much faster than the development of
non-spatial strategies [60]. Thus, spatial learning should
permit subjects attempting to solve a spatial memory
test to perform more quickly than subjects using non-
spatial strategies.
The aim of the present study was to extend our
previous studies on the role of the hippocampal forma-
tion in spatial learning processes [37] and to clarify
whether any spared abilities in hippocampal lesioned
animals are due to the sparing of spatial memory
capacities, or are consequences of improved non-spatial
strategies. Based on a detailed time study showing that
lesioned animals performed much slower than normal
subjects in an identical task, we expected to be able to
differentiate spatial and non-spatial strategies in solving
a reference or working memory task in control versus
lesioned subjects. This would enable us to demonstrate
whether dorsal hippocampal lesions spared either spatial
or non-spatial strategies in rats permitting to solve a
reference or working memory task. In the present
experiment, we used variants of water-maze procedures
to extend Whishaw et al.’s analysis of the role of
allocentric and idiocentric strategies in spatial memory
in rats with hippocampal lesions. As the nature of the
spatial memory impairment appears to vary depending
on the localization of the lesion in the hippocampal
formation [13] or afferent and efferent pathways [6], we
chose to operate rats at the level of the dorsal
hippocampus, which is recognized as a crucial area of
the hippocampus for spatial memory impairment [3,28].
Our hypothesis was that hippocampal lesioned rats
would have difficulty in learning or recalling informa-
tion about spatial locations and how to reach them; that
this would result in a clear navigational deficit; but that
the rats would be able to compensate for this deficit by
using an appropriate strategy, although they would
therefore require more time than normal rats to solve
the task. We therefore compared controls with dorsal
hippocampal lesioned rats that were given either a
normal acquisition task (16 trials) or an extended
training (64 trials), to determine their ultimate perfor-
mance capabilities. We carried out probe tests as
additional assessments of spatial learning; and we
subsequently retrained the animals on a spatial working
memory task. This provided a further test of the
lesioned rats’ use of allocentric and idiocentric strate-
gies.
2. Materials and methods
2.1. Subjects
Twenty-four male Wistar rats (Zur:WIST[HanIbm],
Institute of Toxicology, Schwerzenbach, Switzerland),
approximately 2.5 months old and weighing approxi-
mately 300 g, were used in this experiment. They were
housed four to a cage under a reversed light /dark cycle
(lights on: 19:00 /07:00) with free access to food and
water. After surgery, rats were individually caged.
2.2. Surgery
2.2.1. Dorsal hippocampal electrolytic lesion
The rats were allocated to two groups: 14 dorsal
hippocampal operated (DHE) and 10 sham operated
(Sham). Rats were anaesthetized with 1 ml/kg body
weight of pentobarbital (50 mg/ml) and placed in a Kopf
stereotaxic frame. An incision was made in the scalp to
expose the skull. The vertical coordinates of bregma and
lambda were measured in order to align them in the
same (level head) plane, and a square hole approxi-
mately 3 /4 mm was drilled on each side of the skull
overlying the dorsal hippocampus. Bilateral electrolytic
lesions were made using a 0.3 mm stainless steel
 B. Pouzet et al. / Behavioural Brain Research 133 (2002) 279 /291
electrode used as cathode, insulated except for the tip
(0.5 mm). The anode was a clip fixed on the left subject’s
ear. A constant current DC source was used. Rats
received three bilateral lesions using a 2 mA, 15 s current
at the following coordinates, in mm, posterior (P) to
bregma, lateral (L) to bregma and ventral (V) to dura: P
2.5, L 1.4, V 3.8; P 3.6, L 1.8, V 3.4; P 4.7, L 2.8, V 3.2
[33]. The electrodes were left in place for 30 s before
being retracted from the brain. Sham operated rats
underwent the same surgical procedure, but the electro-
des were inserted 1.2 mm ventral to dura and no current
was passed. Rats were allowed to recover for 2 weeks in
their animal room. One animal did not survive the
recovery period.
2.3. Histology
2.3.1. Gallyas fiber and cresyl violet stains
After the completion of behavioral testing, all hippo-
campal lesioned and five sham operated rats were
anaesthetized with an overdose of equithesin and
exsanguinated transcardially with 50 ml of 0.9% NaCl,
followed by a perfusion with 200 ml of 4% formalin. The
part of the brain at the level of the hippocampus was
post fixed in 30% sucrose in phosphate buffered saline
for 48 h and cut in 40 mm coronal sections on a freezing
microtome. For the examination of the hippocampal
lesions, every fourth section through the hippocampus
was mounted on gelatin coated slides and stained with
cresyl violet. After staining, the sections were dehy-
drated through an alcohol series, cleared with xylene,
and coverslipped with Eukitt (Kindler, Freiburg, Ger-
many). Subsequently, the sections were studied with a
Zeiss Axiophot light microscope to verify the location
and extent of the lesions (according to the atlas of
Paxinos and Watson [33]).
2.4. Apparatus and procedure
2.4.1. Morris water maze
The water maze was a circular tank 2 m in diameter
and 0.6 m in height, made of Fiberglas and painted
black. It was positioned in the middle of a well-lit testing
room (3 /4.9 /2.9 m) enriched with distal visual
stimuli. The bottom of the maze was raised 0.45 m
above the room floor. At the beginning of each day, the
tank was filled with a mixture of cold and hot tap water
to a depth of 0.3 m, and the water temperature was
maintained at 219/2 8C. A stable circular platform,
measuring 11 cm in diameter and painted black, was
submerged 2 cm below the surface of the water hidden
from the rat’s view. It had a rough surface, which
allowed the rat to climb onto it easily once its presence
was detected. A separate white circular disk, also
measuring 11 cm in diameter, could be mounted on
top of the hidden platform so that it was 10 cm above
281
the water surface. When in place, the white disk served
as a distinct visual cue for the location of the otherwise
hidden platform. Four points, equally spaced along the
circumference of the pool, were arbitrarily assigned as:
N, E, S, W. These points served as the starting positions
at which the rat was lowered gently into the water, with
its head facing the wall of the water maze. The area of
the pool was also conceptually divided into four
quadrants (NE, SE, SW and NW) of equal size. A
video camera, connected to an image analysis system
(HVS Image, UK) which in turn was connected to a
microcomputer running the HVS maze software, was
mounted above the center of the water maze. The swim
path of the animal was tracked, digitized and stored for
subsequent behavioral analysis using the same software.
Each trial was started and ended manually by the
experimenter, who operated a remote switch connected
to the microcomputer.
2.4.2. Reference memory task
The reference memory water maze task consisted of 5
stages organized as follows: 4 (Group A) or 16 days
(Group B) of acquisition with a hidden platform, 1 day
of probe test, 4 days of reversal, 1 additional day of
probe test and finally 3 days of visible platform.
2.4.2.1. Acquisition. Rats were given four trials per day
with a submerged platform that the rats could climb
onto, to escape from the water. On each of the four
trials, a different starting point (varied among N, E, S
and W) was used and the location of the escape platform
was fixed (in the middle of quadrant NW, 38 cm from
the wall). The starting points were different for con-
secutive trials. At the beginning of a trial, the rat was
placed into the water at the start location. A trial ended
when the rat escaped onto the platform and the escape
latency for each trial was recorded. If a rat failed to
escape within 90 s, it was either guided to the platform,
or placed onto it, by the experimenter. On such trials, an
escape latency of 90 s was recorded. The rat was allowed
to spend 15 s on the escape platform and then placed for
20 s in a holding cage before the next trial began,
resulting in an inter-trial interval of 35 s. At the end of
the session, the rat was dried with a towel before being
returned to its home cage.
2.4.2.2. First probe test. In this 1-day test, the escape
platform was removed from the water maze. The animal
was allowed to swim for 60 s before being removed from
the maze.
2.4.2.3. Reversal. Rats were given four trials per day
similar to those described for the acquisition, but the
escape platform was located in a novel position,
opposite the location used for the acquisition trials (in
the middle of quadrant SE, 38 cm from the wall).
282 B. Pouzet et al. / Behavioural Brain Research 133 (2002) 279 /291
2.4.2.4. Second probe test. Identical to the first probe
test.
2.4.2.5. Visible platform. Rats were given four trials per
day similar to those described above for the acquisition,
but the escape platform was made ‘visible’ by mounting
a visual cue on top of it. The starting point was constant
across trials, but the location of the escape platform
varied among three possible positions (in the middle of
the quadrant NW, NE or SW, 38 cm from the wall). The
positions were different for consecutive trials, and a new
starting point was fixed every day.
2.4.3. Working memory task
The working memory water maze task consisted of 9
days of acquisition.
2.4.3.1. Acquisition. Rats were given four trials per day
similar to those described for the acquisition of the
reference memory task, but a new platform location was
fixed every day and a different starting point (varied
among N, E, S and W) was used for each trial. Nine
platform positions were possible, either in the middle of
quadrant NW, NE, SW or SE, 38 cm from the wall, or
adjacent to the wall, midway between each pair of
starting points. The last platform location was located at
the center of the pool.
2.5. Experimental design
Twenty-three rats (thirteen lesioned, ten sham) were
run in the reference memory task. Eleven rats (six
lesioned, five sham) previously run in the reference
memory task were run in the working memory task. For
the reference memory task, the total batch of rats was
subdivided on day 4 after a common acquisition training
into two groups: Group A (Group A; six DHE
/ five
Sham) received no further acquisition training (4 days in
total), and group B (Group B: seven DHE
/ five Sham)
received a further 12 days of acquisition, making 16 days
in total. Rats were matched for their mean latencies to
reach the escape platform during the four acquisition
days prior to their allocation to Group A and B. Group
A but not Group B was subsequently tested in the
working memory task.
After the completion of behavioral testing, all of the
operated animals and five randomly chosen sham
operated rats were analyzed histologically.
2.6. Data analysis
The data were analyzed using an analysis of variance
(ANOVA), calculated with the StatView and Super-
ANOVA software system (Abacus Concepts, Inc., Berke-
ley, CA, 1992). We present escape latency data. Parallel
analyses were conducted to compare path lengths and
swim speeds, but are not presented here, because, results
for path lengths were always consistent with those from
the latency analyses, and speed was not affected.
2.6.1. Reference memory task visible platform
Data were analyzed by 2 /3 /4 (Lesion /Day /
Trial) ANOVAs of escape latency for the visible plat-
form session.
2.6.1.1. Acquisition and reversal. Data of the four first
days of the acquisition sessions were analyzed by 2/
2 /4 /4 (Lesion /Training /Day /Trial) ANOVAs
of escape latency. Training stands for the length of
acquisition training: 4 or 16 days. For Group B, the 16
days of the acquisition sessions were analyzed by a 2/
16 /4 (Lesion /Day /Trial) ANOVAs. Asymptotic
performance at the end of this extended training was
assessed using a 2 /3 /4 (Lesion /Day /Trial) ANO-
VAs that considered only the last 3 days. Data from the
reversal sessions were analyzed by a 2 /2 /4/4
(Lesion /Training/Day /Trial) ANOVAs of escape
latency for both Group A and B.
2.6.1.2. Probe tests. Data were analyzed by 2 /2/4/
6 (Lesion /Training /Quadrant /Block) ANOVAs of
the absolute time spent in each quadrant of the pool
defined as target, adjacent-left, adjacent-right and op-
posite. Block is a repeated measurements factor of six
bins (10 s) that permitted the description of the rat’s
travel over time within a trial. The target quadrant was
the one in which the platform had been placed during
the acquisition or reversal sessions. Since the fourth
quadrant data point is never independent of the other
three, the P values were adjusted to reflect a reduction in
the degrees of freedom for the effect of quadrant and for
the interactions involving the quadrant effect. Finally,
2 /2 /6 (Lesion /Training/Block) ANOVAs com-
pared the absolute times spent in the target quadrant
itself.
All results presented as a factor of day, refer to the
mean latency of the four daily trials.
2.6.2. Working memory task
2.6.2.1. Acquisition. Data of the acquisition sessions
were analyzed by a 2 /9 /4 (Lesion /Day /Trial)
ANOVAs of escape latency. Two similar but separate
ANOVAs were performed using the days with the
platform located at the edge of the wall (4 days), and
the days with the platform located in the center of the
quadrants or the center of the pool (5 days). As for the
reference memory task, all results presented as a factor
of day, refer to the mean latency of the four daily trials.
 B. Pouzet et al. / Behavioural Brain Research 133 (2002) 279 /291
3. Results
3.1. Histological
As can be seen in Fig. 1, which shows both drawings
and a photomicrograph of the brains of lesioned rats, in
rats with electrolytic lesions, the dorsal hippocampus
was always completely lesioned. In one lesioned rat, the
lesion damaged only the dentate gyrus and partially the
CA1 and CA3. This rat was rejected from the analysis.
Some damage at the level of the alveus and the external
capsula was observed in most of the animals, but only
Fig. 1. (A) Photomicrograph of the extent of the dorsal hippocampal
lesion (DHE) and a sham control rat (Sham). Cresyl violet stain. (B)
Schematic reconstruction of the smallest (solid black areas) and the
largest (solid grey areas) extents of damage to the dorsal hippocampal
region and the upper cortex. Coordinates of the horizontal sections are
indicated with reference to bregma according to the atlas of Paxinos
and Watson (1986).
283
minor damage was induced at the level of the fimbria.
The presence of neocortical damage was not taken as
ground for exclusion from the experimental lesion group
[16]. No damage could be discerned throughout the
hippocampus of the sham operated rats. The final
number of rats used in the behavioral analysis was 12
DHE and ten Sham. Six DHE and five Sham rats were
allocated to Group A, and six DHE and five Sham to
Group B.
3.2. Behavioral
3.2.1. Reference memory task
3.2.1.1. Acquisition. Fig. 2 presents the mean latency to
reach the hidden platform for the Sham and DHE rats
over 4 days of training after the matching of animals in
Group A and B. As can be seen, whereas the Sham rats
reduced their latency to find the platform as training
progressed, DHE rats showed no improvement through-
out. This was supported by the 2/2 /4 /4 ANOVA
(Lesion /Training/Day /Trial) which yielded a main
effect of Lesion (F1,18 /13.00, P B/0.005), and a
significant interaction of Lesion /Day (F3,54 /8.01,
P B/0.001). There was no significant main effect of
Training, and no interaction with Lesion (all F ’s B/1).
The overall mean latency collapsed over 4 days of
training, after matching the rats in Group A and B, was
30.819/3.94 and 27.449/6.87 s for the Sham, and
56.629/7.28 and 51.189/7.72 s for the DHE rats,
respectively.
Fig. 3 presents the mean latency to reach the hidden
platform of the Sham and DHE rats of Group B over 16
days of training. As can be seen, whereas the Sham rats
reached a stable latency to find the platform, DHE rats
showed a regular improvement as training progressed. A
2 /16/4 ANOVA (Lesion/Day /Trial) yielded a
main effect of Lesion (F 1,9 /31.02, P B/0.001) and an
interaction of Lesion/Day (F 15,135 /2.38, P B/
Fig. 2. Mean escape latency (in s) to reach a hidden platform during 4
days of acquisition training of the reference memory task for dorsal
hippocampal lesioned rats (DHE) and sham operated rats (Sham),
allocated to Group A and B (after matching based on latency to reach
the hidden platform on day 4).
284 B. Pouzet et al. / Behavioural Brain Research 133 (2002) 279 /291
Fig. 3. Mean escape latency (in s) to reach a hidden platform during
the 16 days of extended acquisition training of the reference memory
task for dorsal hippocampal lesioned rats (DHE) and sham operated
rats (Sham) allocated to Group B.
0.005). A main effect of Day (F 15,135 /8.26, P B/
0.001) showed an overall improvement between days.
For the last 3 days (days 14/16), a three way ANOVA
(Lesion /Day /Trial) of the mean latency to reach the
hidden platform yielded a main effect of Lesion (F 1,9 /
70.02, P B/0.001), but no significant interaction of
Lesion /Day (F B/1.0), which demonstrated a stable
latency for the DHE rats close to that of the Sham
operated rats, although consistently higher, confirmed
by the absence of significant main effect of Day (F B/
1.0).
3.2.1.2. Probe test 1. Fig. 4 presents the absolute time
spent in quadrant 4 of the pool, where the escape
platform was located during acquisition training, in bins
of 10 s for the Sham and DHE rats in Group A and B
over the 60 s of the session.
As can be seen in Fig. 4, the Sham operated rats
quickly chose quadrant NW (target), especially subjects
in Group B, reflecting their extended acquisition train-
ing. It can also be seen that the Sham animals from
Group B gave up after 20 s had elapsed. The DHE rats
from Group A never showed any preference for visiting
the target quadrant, in contrast to the DHE rats from
Fig. 4. Results of the first probe test (after acquisition) showing the
time spent in quadrant NW, where the escape platform was located
during acquisition training, i.e. the target quadrant, over six successive
10-s bins.
Group B, who persevered in the target quadrant. This
was supported by the 2/2/4/6 ANOVA (Lesion/
Training /Quadrant/Block) of the absolute time
spent per quadrant, which yielded a main effect of
Quadrant (F 2,36 /18.29, P B/0.001), and an interaction
of Lesion /Quadrant (F 2,36 /8.04, P B/0.002),
Training /Quadrant (F 2,36 /4.02, P B/0.05), and fi-
nally an interaction of Lesion /Training/Quadrant/
Block (F 10,180 /2.72, P B/0.01). A 2 /2 /6 ANOVA
(Lesion /Training/Block) of the absolute time spent
in quadrant four (target) showed a main effect of Lesion
(F 1,18 /20.63, P B/0.001), of Training (F1,18 /9.56,
P B/0.01), and of Block (F 5,90 /6.22, P B/0.001), an
interaction of Lesion /Block (F 5,90 /2.33, P B/0.05),
and more interestingly, an interaction of Lesion /
Training /Block (F 5,90 /5.12, P B/0.001).
3.2.1.3. Reversal task. Fig. 5 presents the mean latency
to reach the hidden platform, located in a different
quadrant (SE) from the one used in acquisition (NW),
for the Sham and DHE rats in Group A and B over 4
days of training. As had been observed in initial
acquisition, the Sham rats reduced their latency to find
the platform as training progressed, but DHE rats
improved their latency only slightly over the 4 days.
This was supported by a 2 /2 /4 /4 ANOVA
(Lesion /Training/Day /Trial) which yielded a
main effect of Lesion (F 1,18 /85.15, P B/0.001), of
Day (F 3,54 /10.66, P B/0.001), and of Trial (F 3,54 /
6.00, P B/0.002), and an interaction of Lesion /Trial
(F 3,54 /3.29, P B/0.03), and of Day /Trial (F 9,162 /
2.38, P B/0.02). The overall mean latency collapsed over
4 days of reversal training was 20.729/2.79 s for the
Sham and 61.379/6.26 s for the DHE rats in Group A,
and 16.639/2.21 s for the Sham and 54.179/3.34 s for the
DHE rats in Group B.
3.2.1.4. Probe test 2. Fig. 6 presents the absolute time
spent in quadrant 2 of the pool, where the escape
platform was located during reversal training, in bins of
Fig. 5. Mean escape latency (in s) to reach a hidden platform during
the 4 days of reversal training of the reference memory task for dorsal
hippocampal lesioned rats (DHE) and sham operated rats (Sham)
allocated to Group A and B.
 B. Pouzet et al. / Behavioural Brain Research 133 (2002) 279 /291
Fig. 6. Results of the second probe test (after reversal) showing the
time spent in quadrant SE, where the escape platform was located
during reversal training, i.e. the target quadrant, over six successive 10-
s bins.
10 s for the Sham and DHE rats in Group A and B over
the 60 s of the session. From the overall and block
analysis, it appears that the DHE group performed less
accurately than Sham animals, but compared with the
first probe test all groups expressed a low preference for
the target quadrant. The 2/2/4 /6 ANOVA
(Lesion /Training /Quadrant /Block) of the absolute
time spent per quadrant yielded a main effect of Block
(F 5,90 /38.87, P B/0.001), and a significant interaction
of Lesion /Quadrant (F 2,36 /4.86, P B/0.05). A sub-
sequent 2 /2 /6 ANOVA (Lesion /Training /Block)
of the absolute time spent in quadrant 2 (target) showed
a main effect of Lesion (F 1,18 /9.89, P B/0.006),
reflecting the poor performance of the DHE rats. A
further 2 /2 /6 ANOVA (Lesion /Training /Block)
of the absolute time spent in quadrant 4 (opposite
quadrant, target of the acquisition sessions) showed a
main effect of Training (F 1,18 /4.91, P B/0.04), result-
ing from the rats of Group B returning preferentially to
this quadrant.
3.2.1.5. Visible platform. All groups showed a consistent
reduction in escape latency across the 3 days and the
four trials within days. A 2 /3 /4 (Lesion /Day /
Trial) ANOVA on the escape latency measure yielded
no significant main effect of Lesion or interaction (all
P ’s /0.05). There was a significant effect of Day
(F 2,40 /11.81, P B/0.001) and Trial (F 3,60 /14.56,
P B/0.001).
3.2.2. Working memory task
Over the trials and the 9 days, the Sham rats reduced
their latency to find the platform as training progressed,
but DHE rats did not show an equivalent overall
improvement. This was supported by the 2 /9 /4
ANOVA (Lesion /Day /Trial), which yielded a main
effect of Lesion (F 1,9 /34.45, P B/0.001), of Day
(F 8,72 /7.54, P B/0.001), of Trial (F 3,27 /35.50, P B/
0.001), an interaction of Lesion /Day (F 8,72 /2.65,
285
P B/0.02), and an interaction of Lesion /Trial
(F 3,27 /5.98, P B/0.003). The overall mean latency,
collapsed over 9 days of training, was 25.619/0.78 s for
the Sham and 43.279/2.65 s for the DHE rats.
Looking at the pattern of results of the overall
ANOVA day by day, it appeared that the lesioned rats
behaved differently depending on the day and, conse-
quently, on the platform location. Therefore, we ana-
lyzed separately the days on which the platform was
located either at the edge of the wall of the pool (days 2,
4, 6, 8) or in the center of the quadrants and pool (days
1, 3, 5, 7, 9). With respect to the trials for which the
platform was located at the edge of the wall, the between
days (Fig. 7A) and between trials (Fig. 7B) analyses
showed no differences between the lesioned group and
the Sham animals in their mean latency to reach the
hidden platform. This was supported by the 2/4/4
ANOVA (Lesion/Day /Trial), which yielded only a
main effect of Day (F 3,27 /3.92, P B/0.02) and of Trial
(F 3,27 /17.69, P B/0.001), but no main effect of Lesion
(F /1) and no interactions (all F ’s B/2). The overall
mean latency, collapsed over 4 days of training, was
22.869/2.76 s for the Sham and 27.959/3.97 s for the
DHE rats.
In contrast, when considering only the trials for which
the platform was located in the central area of the pool,
the between days (Fig. 8A) and between trials (Fig. 8B)
analyses of the mean latency to reach the hidden
platform demonstrated clear lesion effects. The 2/
5 /4 ANOVA (Lesion /Day /Trial) yielded a main
effect of Lesion (F 1,9 /24.18, P B/0.001), of Day
(F 4,36 /5.16, P B/0.003), and of Trial (F 3,27 /17.63,
P B/0.001) and an interaction of Lesion /Trial
(F 3,27 /4.63, P B/0.01). The overall mean latency,
collapsed over 5 days of training, was 27.819/1.97 s
for the Sham and 55.539/4.84 s for the DHE rats.
Fig. 7. Mean escape latency (in s) to reach a hidden platform shown
for days (A) and trials (B) over the 4 days of the working memory task
during which the escape platform was located at the edge of the
swimming pool (days 2, 4, 6, and 8).
286 B. Pouzet et al. / Behavioural Brain Research 133 (2002) 279 /291
Fig. 8. Mean escape latency (in s) to reach a hidden platform shown
for days (A) and trials (B) over the 5 days of the working memory task
during which the escape platform was located in the center of the
virtual quadrant of the swimming pool (days 1, 3, 5, and 7) or in the
center of the pool (day 9).
Fig. 9. Representative search patterns of dorsal hippocampal lesioned
rats (DHE) and sham operated rats (Sham) from group A (Group A)
and group B (Group B) during the last day of the acquisition training
(day 4 for Group A and day 16 for Group B) and the probe test day in
the reference memory task. The four starting points are indicated by
‘N’, ‘E’, ‘S’ and ‘W’, respectively. The location of the escape platform
(removed for the probe test) used during acquisition training is
represented by a solid circle. The end of an unsuccessful swim path
is marked by an arrowhead.
3.2.3. Spatial strategy
As can be seen in Fig. 9, an extensive training of
lesioned animals (Group B), permitted them to locate
the escape platform as effectively as control animals
who received a short training (Group A). However,
unlike controls, the lesioned animals never swam
straight towards the platform, but instead performed
at least one large loop before targeting the platform.
During the working memory test, the lesioned animals
benefited when the platform was located close to the
wall of the pool rather than being in a more central
Fig. 10. Representative search patterns of dorsal hippocampal le-
sioned rats (DHE) and sham operated rats (Sham) during days 7 and 8
of the acquisition training in the working memory task. The four
starting points are indicated by ‘N’, ‘E’, ‘S’ and ‘W’, respectively. The
location of the escape platform used during acquisition training is
represented by a solid circle. The top two rows show swim paths of rats
with the escape platform located in the center of one of the quadrants
of the pool. The bottom two rows show swim paths with the escape
platform at the edge of the wall.
location (see Fig. 10). When the platform was centrally
located in the pool, the lesioned animals’ large looping
swim courses prevented them from reaching the plat-
form efficiently, compared with the control animals who
improved very rapidly and swam almost straight toward
the platform after the second trial. When the platform
was located close to the edge of the pool, lesioned
animals positively benefited from their looping swim
courses, and were as accurate as the control animals in
finding the platform during and after the second trial.
4. Discussion
Our main findings in these experiments are that the
dorsal hippocampal lesioned rats showed clear ability to
solve the water maze task, as demonstrated by their
gradual decreases in latency to find and climb onto the
hidden platform, even if they never reached the score of
control animals. With extended training, lesioned ani-
mals reached an asymptotic level of performance, but
with a characteristic swim path different from control
swim paths, and were probably incapable of further
improvement to control level of efficiency. We suggest
that this swim path indicates the reliance of the lesioned
rats on idiocentric navigation strategies. As can be seen
in Fig. 9, the search pattern of lesioned animals shows
that following extended training (Group B), they were
 B. Pouzet et al. / Behavioural Brain Research 133 (2002) 279 /291
able to locate the escape platform in a large pool
similarly to control animals who received a short
training (Group A); moreover, lesioned animals with
extended training persevered on this place response task
during the first probe test (DHE-Group B) compared
with controls (Sham-Group B) who covered a larger
area, presumably because they gave up. In the reversal
task, all the hippocampal lesioned rats were as severely
impaired as at the beginning of the acquisition regard-
less of prior acquisition conditions. The working mem-
ory task demonstrated that the tendency toward
impairment resulting from hippocampal dysfunction
was still clear at the end of this long study, but is very
sensitive to the procedure and, more specifically, to the
location of the platform in the pool. Like the impair-
ment during the acquisition of the reference memory
task, this impairment reflected the different strategy
applied by the lesioned group of rats, which allowed
them to benefit when the platform was located close to
the wall of the pool, but disadvantaged them if the
platform was located in the central area of the pool (see
Fig. 10). The longer latency to find the platform cannot
be explained by a lower swimming speed, because, in no
session was there a significant difference in the speed of
the two groups of rats.
Histological analysis showed that the rats sustained
dorsal electrolytic lesions that covered at least 30% of
the hippocampus, which according to Moser et al. [28] is
crucial to obtain a measurable impairment of the latency
of animals to reach a hidden platform in a swimming
pool. The electrolytic lesion completely destroyed the
dorsal Ammon’s horn (the dentate gyrus, and the
hippocampal pyramid cell layers of both regio inferior
and regio superior). Our lesions were therefore sufficient
to produce the expected effect on water maze task
performance, while producing only very limited damage
to the retrohippocampal connection with the striatum
[2], which has been shown to be correlated with spatial
information processing impairments [19,21], as the
fimbria was essentially undamaged. The lesions pro-
duced little subcortical extrahippocampal damage at the
level of the track of the electrode, and the cortical area
surrounding this track. The learning deficiency observed
in this study cannot be explained by reference to these
minor areas of damage. Other previous studies have
demonstrated that similar or larger lesions at this level
of the cortex had no effect in a variety of spatial memory
tasks [16,25,27]. Some of these studies used a paradigm
identical to ours, but their lesions were produced with
more devastating techniques like aspiration, and even so
the authors could not demonstrate impairment of
cortical lesioned animals [25]. Thus, there is no reason
to consider that the learning deficiency observed in our
lesioned animals in comparison to sham animals in
which electrodes were inserted in the cortex, is a
consequence of cortical damage rather than hippocam-
287
pal damages. On the other hand, we can not completely
reject the possibility that the angular bundle was
damaged. Could this have been responsible for the
behavioral deficits in the lesioned animals? Damage at
the level of the angular bundle would mean disruption
of the perforant path from the entorhinal cortex to the
hippocampus. However, we demonstrated in a previous
study that cytotoxic lesions of the entorhinal cortex in
rats did not modify the ability of these animals to solve a
spatial memory task, using the Morris water maze
paradigm with an experimental design similar to the
one use in this study [37]. Consequently, we do not
believe that lesion of the angular bundle, if any, could
explain the memory dysfunction observed in this study
with dorso-hippocampal lesioned animals.
As has been shown by many groups, the hippocampal
lesioned rats were clearly impaired in comparison with
controls [25,53] when they received only a short
acquisition period (Group A), and to repeat Morris’s
comment, we did not need the histology study ‘to know
which of the rats have good lesions’ [24]. Our results are
completely consistent with the suggestion that the dorsal
part of the hippocampus is crucial for spatial learning in
rats. Not only was there a major difference in the latency
to reach the escape platform over the first 4 days
between the sham operated and lesioned rats, but the
former group quickly reduced its latency while the latter
did not improve at all. On the other hand, consistent
with other observations [26,60,62], in Group B, which
received 16 days (64 trials) of acquisition, it appeared
that the lesioned rats were able to improve their latency
to reach the escape platform up to an asymptotic level
after 14 days of training. Thus, dorsal hippocampal
lesioned rats retained the capacity to progress on this
task, but only in a situation comprising repetitions of
the learning event, as already claimed for both spatial
and olfactory paradigms [7,60]. The lesioned animals
never reached the performance level of controls; this
demonstrates that there was nonetheless a lasting spatial
impairment despite the extended training. Moreover, an
analysis restricted to the last 3 days of the acquisition
period showed a consistent lesion effect (P B/0.001) but
without any effect of days (all F ’s B/1), which demon-
strates that both groups of animals (sham operated and
dorsal hippocampal lesioned) did not progress any
further after 14 days of acquisition and that thereafter
their behavioral difference remained stable. These
results also provide evidence that over days, lesioned
animals used a different strategy than the sham operated
rats to locate the escape platform. The swim path
recorded described a trajectory based on the well-
described large loops typical of hippocampal lesions
[12,62]. These loops cost the rats much more time in
progressing over trials and within trials. These observa-
tions are consistent with the suggestion that rats without
hippocampus lack the ability to use a spatial strategy in
288 B. Pouzet et al. / Behavioural Brain Research 133 (2002) 279 /291
learning the task and therefore, shift to a non-spatial
strategy normally not used by controls.
The first probe test session confirmed that lesioned
rats who received an extended training were able to
learn about a platform location. Following 64 acquisi-
tion trials (16 days), lesioned rats searched the correct
quadrant of the pool when the platform was removed,
further confirming that they had learned at least some
form of a place response. We also observed that they
progressed differently from sham operated rats. Sham
operated rats went immediately to the target quadrant
of the swimming pool but gave up looking for the
platform after 20 s had elapsed. In contrast to the sham
rats, dorsal hippocampal lesioned rats required more
time to choose the target quadrant but continuously
persevered on their task, and compared with the sham
rats, almost reached the same level of time per 10-s bins
spent in the target quadrant. As depicted in Fig. 9,
dorsal hippocampal lesioned rats swam some large loops
in the pool and then quickly reduced the diameter of the
loop to be closer to the escape platform, with the
platform always at the center of the loops. In the same
task, sham operated rats went straight to the escape
platform and were consequently much faster.
In some of the subsequent stages of the experiment,
dorsal hippocampal damage was still associated with
severe water maze impairments (thereby demonstrating
the lasting efficacy of the lesion effect). There were
deficits in reversal learning, in the probe test that
followed, and in working memory when the target
platform was near the center of the pool. Intermingled
with these demonstrations of impairment there were
stages where performance was good: these were in the
probe trial at the end of extended acquisition; during
visually guided searching [25,38] (showing that motiva-
tion and motor skills were essentially intact); and in the
working memory task when the platform was located
near the side walls. This overall pattern of results is
readily accounted for by the development of the
characteristic swim paths that hippocampal lesioned
rats demonstrated after extended training. This swim
pattern emerged both in Group B by the end of their
prolonged acquisition training, and in Group A in the
working memory task, which made up the last stage of
the experiment. The paths followed a looping trajectory,
that would make it intrinsically more likely that the rats
would contact platforms located near the side walls
(accounting for the working memory task results), but
was also modifiable in the light of the animals’
experiences of finding the platform. This provides an
account of the performance of the Group B rats in the
probe trial at the end of their extended acquisition, in
which they swam in large loops early in the test, and
then quickly reduced the diameter of the loops. We thus
confirmed that rats with dorsal hippocampal lesions
were perfectly able to localize a spatial location, but not
as quickly as normal rats because, their hippocampal
dysfunction obliged them to counterbalance a severe
spatial cue learning or recall deficit by performing the
task using a more restrictive strategy. The spatial
mapping theory proposed by O’Keefe and Nadel
describes the hippocampus as a cognitive map */a
memory system that computes and stores information
about allocentric space [31], but Nadel has argued that
‘there should be many so-called spatial abilities that
would be unaffected by lesions in the hippocampal
formation, and a rather select class of such abilities that
are affected’ [29]. Our own results suggest that the rats’
remaining abilities to locate the escape platform are
likely to have depended on non-spatial strategies, which
were sufficiently robust to permit the lesioned rats to
learn about the platform location under our training
and testing conditions. It could be suggested that
lesioned rats used the pool wall as proximal cues to
learn the platform location and to solve the spatial
memory task. Such a suggestion might account for the
result obtained during the reference memory task with
lesioned animals following the edge of the wall. How-
ever, this possibility could hardly explain the use of
concentric loops to solve the working memory task.
On the second probe test, the behavior of the lesioned
rats in Group A was identical to that in the first probe
test and they showed no preference for visiting any one
of the four quadrants of the pool. The sham operated
rats, in contrast, returned to the quadrant in which the
escape platform was located during the reversal task
(target quadrant). In Group B, it seems that as a result
of the extended training during the first acquisition
session inducing an inability to inhibit previous learning,
sham operated rats were impaired in learning the new
task. Sham operated rats were able to improve their
latency over the 4 days of the reversal session, but this
result could not be confirmed on the following probe
test [18].
Our results in the working memory task complement
those obtained by Whishaw [59]. He reported that, in a
task in which the animals had to reach food cups located
at equal distances around the perimeter of a large table,
comparable to the escape platform that the rats had to
find in our experiment, rats with fimbria /fornix lesions
performed better than the control rats in terms of time
scores. If a task with the food cups located more
centrally to the table had been designed, one might
expect results identical to ours; i.e. the lesioned rats
would perform worse than the controls. On the con-
trary, in our study when the analysis was performed
considering only the days with the platform located in
the center of the pool or the center of the quadrant,
there was a significant effect of trial, and a significant
interaction of lesion with trial, suggesting that the dorsal
hippocampal lesioned rats were only able to progress
when they had a chance of finding the platform; in other
 B. Pouzet et al. / Behavioural Brain Research 133 (2002) 279 /291
words, they needed at least some successes to be able to
progress through this working memory task. It is worth
noting that other groups using different spatial working
memory tasks [30] have shown that rats with hippo-
campal dysfunction also appeared to be able to improve
their performance in a working memory test [13],
depending on the procedure applied.
In summary, we consider that hippocampal lesioned
rats are still able to discriminate their location in space,
and adjust their behavior accordingly, at least under
some conditions. However, there is no doubt that they
nonetheless have considerable difficulty in using envir-
onmental cues or in integrating their spatial experiences
into efficient behavioral response repertoires. Our
results are consistent with the proposal that the rats
with hippocampal lesions lost their capacity to use
spatial cues efficiently, but in part compensated for
this deficit by using idiocentric strategies. Our conclu-
sions are also consistent with an interesting study by
Pearce et al. [34], who demonstrated that excitotoxic
hippocampal lesioned rats were still able to appreciate
the direction in which a hidden platform could be found
with respect to a landmark located in the swimming
pool. These authors specified that it is difficult to
describe the source of this directional information, but
they suggested that it could be due to an internal sense
of direction. This is a slightly different account from
that provided Whishaw [60], who reported that rats with
ibotenic hippocampal lesions or electrolytic fimbria /
fornix lesions could perform a probe test similarly to
normal rats after extensive training on a place task,
using a stronger search behavior. We demonstrated that
rats with dorsal hippocampal lesions performed a probe
test similarly to sham operated rats only if the behavior
of the rats is analyzed over the entire probe test session.
The more detailed analysis of the first probe test session
over time blocks highlighted the fact that dorsal
hippocampal lesioned rats had developed a different
strategy [9] which was certainly idiocentric and which
cost them more time to solve the task than control rats
which are presumably able to use both allocentric and
idiocentric strategies. A final question remains: are the
distinctive response patterns we and others have ob-
served the direct consequence of the lesion and the cause
of the behavioral deficits that are reliably reported, or
does the causal chain go in the opposite direction, such
that the spatial deficits reliably reported are the direct
consequence of the lesions, and the residual abilities that
we see are the animals’ attempts to use other, less
appropriate, brain systems to compensate for the spatial
impairments? The demonstration that hippocampal rats
in the water maze behave like normal animals when a
curtain is fixed around the pool to hide extra-maze cues
[12,50] clearly implies that the strategy deployed by
animals with hippocampal dysfunction is not a conse-
289
quence of a changed motor response as such but an
inability to use cues distributed around the pool.
Acknowledgements
This work was supported by the Swiss Federal
Institute of Technology Zurich and the Swiss National
Science Foundation (Grant number: 3142009.94/2). The
authors thank the animal facility team for their care of
the animals, and E. Weber for her histological prepara-
tions.
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