Download Place cells, neocortex and spatial navigation: a short review

Journal of Physiology - Paris 97 (2003) 537–546
www.elsevier.com/locate/jphysparis
Place cells, neocortex and spatial navigation: a short review
Bruno Poucet *, Pierre-Pascal Lenck-Santini, Vietminh Paz-Villagr
an, Etienne Save
Laboratory of Neurobiology and Cognition, LNC/CNRS, 31 Chemin Joseph-Aiguier, 13402 Marseille Cedex 20, France
Abstract
Hippocampal place cells are characterized by location-specific firing, that is each cell fires in a restricted region of the environment explored by the rat. In this review, we briefly examine the sensory information used by place cells to anchor their firing
fields in space and show that, among the various sensory cues that can influence place cell activity, visual and motion-related cues
are the most relevant. We then explore the contribution of several cortical areas to the generation of the place cell signal with an
emphasis on the role of the visual cortex and parietal cortex. Finally, we address the functional significance of place cell activity and
demonstrate the existence of a clear relationship between place cell positional activity and spatial navigation performance. We
conclude that place cells, together with head direction cells, provide information useful for spatially guided movements, and thus
provide a unique model of how spatial information is encoded in the brain.
Ó 2004 Elsevier Ltd. All rights reserved.
Keywords: Spatial memory; Navigation; Place cells; Sensory systems; Hippocampus; Parietal and retrosplenial cortex
1. Introduction
A survey of the neural substrates of spatial processing clearly highlights the important contribution of
the hippocampus. Critical evidence for the hypothesis
that the hippocampus carries out computations involved in navigation was initially provided by the
discovery of place cells. Place cells are cells whose
firing is strongly correlated with the location of a
freely moving rat in its environment [42]. Anatomically, place cells are pyramidal complex-spike neurons
that are found in the CA1 and CA3 areas of the
hippocampus [11]. The existence of place cells converges with lesion evidence to suggest that the hippocampus might play a critical role in the processing of
spatial information [43]. In this regard, place cells
provide a model of how such information is encoded
at a neural level.
An important issue that immediately arises is the
origin of the place cell signal. Although much is known
about the sensory information that is required to shape
the activity patterns of place cells [48], the pathways
*
Corresponding author. Tel.: +33-49-116-4469; fax: +33-49-1714938.
E-mail address: [email protected] (B. Poucet).
0928-4257/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.jphysparis.2004.01.011
that are involved in the transmission of this information are still poorly understood. Because the entorhinal
cortex is the major area relaying the sensory information to the hippocampus, one must suspect that the
cortical information reaching the entorhinal cortex is
important for place cell firing. Surprisingly, however,
only a few studies have looked at the contribution of
neocortical areas that are connected directly or indirectly to the entorhinal cortex and hippocampus to the
generation of the place cell signals. The first aim of this
article is to briefly review some recent studies that have
been conducted along these lines. Even though lesion
studies of place cell activity make up an incomplete
picture at this stage, they have revealed several
important aspects of the neocortical contribution to
place cell spatial firing.
Another important question is whether place cells are
involved in navigation at all. Although there is voluminous evidence from the lesion literature that removing
the hippocampus induces strong and permanent deficits
in a wide variety of spatial tasks [43], the way hippocampal place cells are involved in navigation is still a
matter of debate. The second aim of this review is to
summarize recent experiments performed in our laboratory that deal with this point and demonstrate the
existence of a clear functional relationship between place
cell activity and spatial navigation.
538
B. Poucet et al. / Journal of Physiology - Paris 97 (2003) 537–546
2. Basic properties of place cells
Place cells are characterized by stable, spatially limited ’’firing fields’’. A place cell fires rapidly when the
rat’s head is inside its field and is usually silent elsewhere
in the environment. In general, place cells fire independently of the direction faced by the rat: place cell discharge recorded from a rat exploring a circular arena
varies only with the rat’s location [39]. This property
strongly suggests that the best correlate of place cells is
the animal’s location in the current environment, and
not a restricted ‘‘sensory view’’ of that environment.
Simple manipulations of the sensory environment in
which the rat is moving reveal that several sensory
channels contribute in providing meaningful input to the
hippocampal place cell system. In familiar environments, place cell firing relies predominantly on visual
information. In the absence of visual information, other
cues, such as olfactory cues, may become important [56].
Another type of information previously suggested to
be useful for updating place cell activity in the absence
of visual cues is motion-related information [13,15,28,
40,49,58]. According to this hypothesis, hippocampal
place cells would update their activity by keeping track
of the rat’s movements in space based on signals stemming from the vestibular and proprioceptive systems as
well as from motor efference copy [28]. However, this
strategy, known as path-integration [32] tends to accumulate errors so that if no re-calibration occurs, the
cumulative error becomes so large that any further
computation is inaccurate [9,13,29,31]. This is confirmed
by the finding that, when the use of external cues is
precluded, motion-related (or idiothetic) cues alone are
not sufficient to support spatially stable place cell firing
in the long term [56].
However, idiothetic information does contribute to
place cell firing as shown by our observation that blind
rats have normal firing fields [55]. In this study, place
cell activity was recorded while rats blind from an early
age were freely moving in a cylinder arena that contained three three-dimensional objects at fixed positions
near the wall of the apparatus. The cylinder itself was
positioned at the center of a curtained area. The objects
were different in size, shape and texture, so that they
could be used as spatial landmarks likely to help rats to
localize themselves in space. Blind rats had place cells
very similar to those recorded from sighted rats, and, as
in sighted rats [5], their firing fields depended on the
objects intentionally placed into the recording cylinder
as spatial landmarks. That is, the object set exerted
powerful control on firing field locations as shown by
the observation that rotation of the objects was followed
by equivalent rotation of firing fields. Thus, place cell
activity in blind rats relied on the object locations and
was updated on the basis of internally generated, motion-related cues resulting from the rat’s movements in
space. By inference, blind rats were aware of the object
locations and were able to use motion-related information cues to update their own position relative to the
objects, a suggestion that was confirmed by detailed
analyses of their behavior [16]. It is likely that motionrelated cues are also used by sighted rats for the ongoing
calculation of their position in space. One advantage of
such automatic ongoing calculation is that it puts less
burden on attending to the outside environment. However, its trade-off is that it requires occasional re-calibration based on external cues so as to correct for
cumulative errors resulting from idiothetic computations [48].
In summary, even though visual information is
important, several inputs from motion-related systems
and other non-visual modalities contribute to spatially
coherent place cell firing. In the absence of vision,
olfactory and tactile cues provide enough information to
anchor the hippocampal representation in combination
with motion-related cues.
3. Effects of neocortical damage on place cell activity
3.1. Entorhinal lesions
As noted in the introduction, few studies have addressed the effects of cortical lesions on place cell activity
in spite of the strong connections that exist between the
hippocampus and the cortex (see Fig. 1 for a summary
of the regions of interest). The first experiment was
performed by Miller and Best [30] who compared the
firing patterns of place cells in normal control rats and
in rats with lesions of the entorhinal cortex (lesions of
the fornix, also included in this study, are not further
discussed here as these fibers do not carry cortical signals). The animals were trained to run a radial maze for
food reward while their neuronal activity was recorded.
Lesions generally reduced the number of cells with
positional correlates and the firing of those cells with
clear place correlates was less robust than in normal
control rats. More importantly, there was a change in
the type of control exerted by environmental cues over
the firing fields following 90° rotations of the maze; all
units from normal rats continued to fire in the same arm
Hippocampus
Subiculum
Retrosplenial
cortex
Parietal
cortex
Perirhinal
cortex
Visual
cortex
Entorhinal
cortex
Fig. 1. Schematic representation of major neocortical connections to
the hippocampus.
B. Poucet et al. / Journal of Physiology - Paris 97 (2003) 537–546
relative to the distal cues from the laboratory while only
a tiny percentage of cells did so after entorhinal damage.
In fact, most cells (65%) recorded from rats with entorhinal damage lost their positional correlate. The
remaining cells (about 30%) still had firing fields but
these were observed to stay in register with the physical
arm of the maze (i.e. their location rotated with the
maze rotation). This initial study indicates that loss of
transmission of cortical information through the entorhinal cortex results in marked changes in place cell
activity. This information seems to concern a variety of
cues some of which might be related to the physical
properties of the maze. Although informative, this study
clearly needs to be replicated using up-to-date recording
methods. This would permit better documentation of
the effects of entorhinal cortex damage on several aspects of place cell discharge that it was impossible to
study twenty years ago.
3.2. Perirhinal lesions
More recently, Muir and Bilkey [37] have addressed
the potential contribution of another cortical area, the
perirhinal cortex. This area appears to play a key role in
memory [23–25], and is connected to the hippocampus
both directly and indirectly via the entorhinal cortex
[59]. In return, the perirhinal cortex receives projections
from the entorhinal cortex, but also from widespread
neocortical areas including the frontal, parietal, temporal and occipital regions as well as the retrosplenial
cortex [1,2]. The firing characteristics of place cells were
examined in control rats and in rats with lesions of the
perirhinal cortex while they were foraging in a rectangular environment. Perirhinal damage did not reduce
the number of cells that could be recorded nor did it
affect place cell firing characteristics. A major effect of
perirhinal damage was observed, however, when the
same place cells were recorded after a delay of 24 h.
While the firing fields of all place cells recorded from
control rats were similar in location across successive
sessions, many fields from rats with perirhinal cortex
lesions were found to shift position across the delay
period. Therefore, even though the perirhinal cortex is
not necessary for the initial formation of firing fields in
the hippocampus, it seems required for the maintenance
of stable fields over time. This result suggests a role of
the perirhinal cortex in the reliable identification of the
current environment, based on the memory of cues and
associations of cues from that environment.
3.3. Visual cortex lesions
Because hippocampal place cells rely on both visual
and motion-related information to maintain stable firing fields (see above), we recently have started to look at
the consequences of neocortical damage in areas con-
539
cerned with the processing of such information. As
shown in the previous section, place cell activity is not
strongly altered when the rat is deprived of vision early
in its life [55]. Even though the preserved properties of
place cell firing can be explained by compensation
mechanisms such as learned sensory substitution, this
finding suggests that vision might not be so essential
for navigation, a conclusion supported by the observation that spatial performance in blind rats is not profoundly impaired in water maze navigation [22]. In view
of the relatively preserved spatial skills in blind rats,
it seems therefore somewhat unexpected that ablation
of the visual cortex induces a strong deficit in radial
maze performance [10,26]. A direct comparison of rats
with visual cortical damage and blind rats revealed a
much stronger impairment in the brain-damaged rats
[12]. This impairment suggests that the visual cortex
might accomplish some central function in spatial processing. To examine this possibility, we recorded place
cells from rats with lesions of the visual cortex [47]. The
procedure was similar to that used by Save et al. [55]
with blind rats (see Section 2), therefore making it
possible to compare place cell discharge in rats with
visual cortex lesions and normal sighted or early blind
rats. Thus, place cell activity was recorded while rats
were freely moving in a cylinder with three objects near
the wall of the apparatus.
Rats with visual cortex lesions were found to have
functional place cells whose fields were similar to the
fields recorded from rats with an intact cortex and were
stable across time. Contrary to both normal sighted rats
and early blind rats [5,55], however, place cells from rats
with visual cortex lesions were shown to use threedimensional objects much less efficiently for the spatial
anchoring of firing fields. In rats with an intact visual
cortex, rotation of the objects is followed by equivalent
rotation of firing fields in a vast majority of instances.
That is, the object set exerts almost ideal control on
firing field locations. We found that this control is dramatically reduced in rats with visual cortex lesions: in
these animals, rotations of the object set only rarely
induced coherent field rotations. Thus, control rats used
the objects within the recording cylinder as the reference
frame for anchoring their firing fields whereas rats with
visual cortex lesions used some uncontrolled, but stable
cues stemming from the experimental room. Because
their inability to use the objects was partial, however,
this effect can be best described as an alteration rather
than a total disruption of the process that selects the
spatial reference frame. A simple explanation of this
effect is that rats with visual cortex damage may rely
on non-visual distant information (such as odors or
sounds) to set the reference direction for firing fields.
However, a more interesting possibility is that the visual
cortex might be involved in the initial calibration of the
spatial reference frame used by the place cell system. For
540
B. Poucet et al. / Journal of Physiology - Paris 97 (2003) 537–546
example, it might be required for selecting the visual
cues to use as landmarks. Interestingly, disrupted cue
control over place cell firing fields is also observed after
lesions of the postsubiculum [60], thus raising the possibility that both the visual cortex and postsubiculum
work together to provide the angular reference direction
for orienting the hippocampal spatial map. Such a
function would explain the altered cue control properties of place cells as well as the spatial deficits seen after
visual cortex lesions [12,55].
3.4. Retrosplenial and parietal cortex lesions
Both the parietal and retrosplenial cortices are
hypothesized to contribute to the integration of visuospatial and motion-related cues for navigation [33,57].
These two structures receive visual afferents from secondary visual sensory cortical regions and are connected
to a number of structures in the hippocampal formation
such as the entorhinal cortex, the subiculum and the
perirhinal cortex [1,64]. In addition, lesion of either
cortical region has been shown to induce deficits in
spatial tasks [14,57]. Accordingly, the parietal and retrosplenial cortical areas might exert an influence over
hippocampal place cell activity. This has been confirmed
in a recent study by Cooper and Mizumori [6] who
examined the effects of temporarily inactivating the
retrosplenial cortex on place cell activity in rats performing a radial maze task. The consequences of such
inactivations were examined during acquisition and
during retention of the task. In addition, for the retention group, the animals performed the task in light or in
darkness. The authors found that retrosplenial inactivations disrupted the stability of firing fields, i.e. the
preferred location of firing fields shifted to unpredictable
locations of the maze, in both acquisition and retention.
Interestingly, these firing pattern modifications were
correlated with performance deficits during acquisition
and during retention in darkness only. This suggests that
cooperation between the retrosplenial cortex and the
place cell system is required for different stages of spatial
information processing, including initial integration of
visuo-spatial and movement-related sensory cues and
the use of mnemonic visuo-spatial information in the
absence of environmental cues [33]. Interestingly, the
retrosplenial cortex is part of a large network of connected brain structures that includes the postsubiculum
and the anterior thalamic and lateral dorsal thalamic
nuclei. All these areas contain head direction cells that
fire when the rat’s head faces a specific direction independently of its location [3,60]. Since head direction cells
and place cells are strongly coupled [18], it is possible
that the effects of retrosplenial inactivations on hippocampal place cells were mediated by the disruption of
the head direction system. In support of this hypothesis,
lesions of the postsubiculum are observed to disrupt
cue control of hippocampal firing fields (unpublished
observations reported in [60]).
The parietal cortex (formerly area 7 in Krieg’s terminology [19]) has reciprocal connections with the retrosplenial cortex and is indirectly connected to the
hippocampus [62]. In our laboratory, we have recently
examined the effects of parietal cortex lesions on place
cell activity (unpublished data). Parietal-lesioned and
control rats were allowed to forage freely for randomly
scattered pellets in a recording cylinder. Three objects,
similar to those used in a previous study [47], were
placed against the wall of the cylinder to serve as landmarks in a cue-controlled environment. Contrary to
retrosplenial inactivations, parietal cortex lesions did
not impair firing field stability in standard conditions. In
addition, rotation of the object set was accompanied by
an equivalent rotation of firing fields, showing that
parietal rats used the objects to maintain firing field
stability. The most dramatic effect of parietal cortex
damage was observed during the session that followed
the rotation test, when the objects were removed in
presence of the animal. In the absence of object landmarks, a substantial number (48%) of firing fields in
parietal-lesioned rats (15% in control rats) shifted back
to the initial, standard, pre-rotation location (Fig. 2). In
control rats, most firing fields remained stable relative
to the rotation session (36%) or disappeared, i.e. cells
stopped firing (27%). Thus, these results suggest that
field stability in control rats was strongly dependent on
the objects whereas field stability in parietal-lesioned
rats could be placed under the control of background
cues when the objects were removed. This raises the
possibility that the parietal cortex is involved in the
processing of proximal landmarks and contributes to
provide some stable local frame of reference to the
hippocampal place cell system. Another complementary
explanation is that parietal-lesioned rats rely on background cues because they are unable to use motionrelated cues to maintain firing field stability in absence
of objects. Interestingly, these results together with those
obtained in rats with damage to the visual cortex suggest
that the processing of visuo-spatial information along
the occipito-parietal axis results in the calibration and
selection of the reference frames used by the place cell
system to anchor stable firing fields.
3.5. Commentary
This short review of lesion-induced alterations of
the place cell signal reveals a striking parallel with the
behavioral spatial deficits that result from damage to the
corresponding cortical areas. Virtually any cortical area
shown to be important for performance of spatial navigation tasks can be demonstrated to be also important
B. Poucet et al. / Journal of Physiology - Paris 97 (2003) 537–546
541
Fig. 2. Firing rate maps of two place cells recorded for five consecutive sessions. Three objects (shown as a white square, a black circle and a gray
square, respectively) were placed directly into the recording cylinder (shown as a large circle) to serve as spatial landmarks. In each map, locations in
which no firing occurred during the whole session are white. The highest firing rate is coded as black, and intermediate rates are shown as light gray
and dark gray from low to high. The first two sessions were conducted with the object set in a standard position. The third session was conducted
with the object set rotated 90° CCW from the standard position. The rat was removed from the cylinder between each session (indicated by a vertical
arrow) except between the third and fourth sessions. Before the fourth session (‘‘Removal’’), the three objects were removed from the cylinder. Thus,
the rat could locate itself only based on self-motion cues combined with odors possibly remaining in the cylinder, or alternately on uncontrolled static
background cues from the laboratory. The last session was conducted with the objects back to their standard positions. Cell 1 (top row) was recorded
from a normal rat; its field rotated appropriately in the third session and was spatially stable after object removal. Cell 2 (bottom row) was recorded
from a rat with bilateral parietal cortex damage; its field also followed the object rotation in the third session. However, it rotated back to its initial
placement as soon as the objects were removed. A majority of cells from parietal rats showed this pattern, which suggests a failure to use of selfmotion cues (see text for further details).
for the generation of normal place cell characteristics.
Because spatial behavior is so easily disrupted by brain
damage, it is often difficult, however, to determine the
exact nature of the processing stage that has been affected by the lesion. With regard to this point, considering the place cell system as a model system that,
among other tasks, is a spatial information processing
module and looking at the changes in place cell discharge provides a way of characterizing cortical contributions in a much better defined manner. Although at
this stage it may be speculative to propose specific
functions for each cortex, it appears that the effects of
damage to each cortical area on place cell discharge
match the deficits expected from known neuroanatomical and behavioral data.
4. Relationships between place cell activity and spatial
behavior
Place cells continuously indicate the rat’s location in
the current environment. This property is the cornerstone of the cognitive map theory of hippocampal
function [43]. This theory is further supported by the
observation that destruction of the hippocampus disrupts the performance of rodents in a wide variety of
spatial tasks [16,36,54]. Thus, both unit recording
studies and lesion work converge to indicate a central
role for the hippocampus in map-based navigation.
Other evidence suggesting that place cells are the
essential units of the putative environmental map come
from the observation that manipulations that produce
alterations of place cell properties also impair performance in place navigation tasks. For example,
genetically modified mice with an impaired long-term
potentiation (LTP) as well as rats with a treatmentinduced impaired LTP have abnormal place cells and
reduced performance in place navigation tasks [4,17,27,
34,51,52]. Thus, treatments that generate place cell
abnormalities seem to reliably induce abnormalities of
spatial navigation.
Although these findings support the mapping theory,
the weaknesses associated with lesion-type methods
imply that a more direct approach is required to show
how the place cell signal relates to behavior in a normal
animal. Probing the relationship between place cell discharge and the rat’s spatial behavior requires concomitant recording of both events. Surprisingly, the existence
of a direct relationship between place cells and navigation was only anecdotally noticed [44]. Rats were trained
to reach one arm of a plus-shaped maze on the basis of
its location relative to a set of extra-maze cues. On a few
occasions, these cues were removed. Under these circumstances, it was found that even on error trials the
rat’s random choice of goal remained in register with its
place cell firing fields, suggesting that place cell activity
and spatial behavior were coupled. To explore this issue
in a more systematic way, we performed two studies
both of which relied on the same underlying principle: if
place cells provide position information useful for performing a spatial task, then behavioral manipulations
that result in the place cell information being out of
register with that task should also lead to incorrect
spatial behavior.
542
B. Poucet et al. / Journal of Physiology - Paris 97 (2003) 537–546
4.1. Place cell activity in a spatial memory task
The contribution of place cell activity was first probed in a spatial alternation task, known to depend on
the integrity of the hippocampus. Rats were trained
to perform a continuous spatial alternation task in a
Y-shaped maze in which the only available landmark
was a prominent white card, positioned between two
arms [21]. In this task, the rats had to alternate between
the two arms of a Y-maze to get a food reward in the
third (goal) arm (Fig. 3A). Once the rats performed well
in the presence of the card (‘‘standard condition’’), place
cells were recorded in several sessions after the card was
rotated or removed. These manipulations were expected
to result, on some occasions, in the angular positions of
firing fields shifting out of register with the positions
seen in the standard condition. Our purpose was to
determine if the rats’ performance was worse when fields
were out of register relative to their standard position.
Overall, the results confirmed the existence of a
strong deterioration in performance when field positions
were inconsistent with the learned task. First, the
number of correct responses was dramatically reduced
with rats being rewarded, on average, half as often than
during sessions with consistent field placements. Second,
the nature of the errors was also different when fields
were out of register with the task, with rats either
repeating incorrect choices of an individual arm or
failing to follow the basic alternation rule to solve the
task. These types of errors reflect a more complete disorganization than just making the most commonly observed alternation (working memory) errors. Third,
erroneous placements of firing fields often predicted
erroneous visits to an individual arm.
Together, these results show that erroneous field
placements were associated with disorganized spatial
behavior. Noticeably, the changes in firing fields concerned only their angular position in the maze: even
though the fields were on the wrong arm relative to the
goal, their radial position relative to the maze center
was correct. In addition, all fields were coherent with
one another when several cells were simultaneously
recorded. Thus, there was no evidence that cue manipulations resulted in the activation of a different representation, as is the case when place cells are recorded in
several differently shaped environments [38]. Instead, the
same place cell representation was active, but was
incorrectly oriented with respect to the spatial task the
rat had to accomplish. Thus, a reasonable assumption is
that the observed behavioral effects were caused by the
mismatch between the orientation of the hippocampal
representation and the learned task, rather than by the
activation of a distinct representation.
Interestingly, very similar findings were observed for
head direction cells whose activity was recently demonstrated to correlate with spatial behavior on a radial
maze [7]. Head direction cells fire only when the rat is
heading at specific directions independently of its current location and are found in several brain areas (such
as the postsubiculum and anterior thalamic nuclei) all of
which have extensive connections with the hippocampus
[60]. Animals implanted for head direction cell recordings were trained to find reward on a particular arm in a
fixed position relative to a visible cue in the room. When
Cue card
C (food)
X
Cue
card
?
F
B
A
(A) Spatial alternation task
X
(B) Place preference task
?
C
X
(C) Principle of behavioral / unit recording studies
Fig. 3. Behavioral procedures used to probe place cell involvement in spatial performance and general principle. (A) The continuous spatial
alternation task [22]. The apparatus is a Y-shaped maze with a large cue card (shown as an arc) as the single spatial landmark. The circle at the end of
arm C indicates the location where the rat was rewarded with a food pellet if it had previously made a correct alternation visit to one of the other two
arms A and B. (B) The place preference task [21]. The apparatus is a cylinder with a single cue card attached to the wall (shown as an arc). The rat
had to enter an unmarked goal zone and stay there to trigger the release of a food reward from a dispenser situated above the cylinder. Since the
released pellet could land anywhere in the cylinder, the rat had to leave the goal area to find the pellet. The small circle shows the goal location in the
Far task. In the Near task, the goal area was beneath the cue card while in the Cue task, it was directly signaled by a black disk on the floor. The rat’s
path to the goal is shown as a continuous line. The path away from the goal to retrieve the food pellet at location Ôx’ is shown as a dashed line. (C)
The general principle of the experiments combining place cell recordings and the analysis of navigation performance is illustrated for the Far task. A
schematic place cell firing field (shown as a set of concentric gray-shaded ellipses) represents the orientation of the hippocampal map. The purpose is
to determine where the rat will search for the goal when a cue manipulation (here a rotation of the cue card) does not produce the expected rotation
of the firing fields (i.e., of the hippocampal map). One prototypical situation in which the hippocampal map often fails to re-orient relative to the
external environment is when the card is rotated in the presence of the rat. Under these circumstances, the goal location indicated by the external
environment (ÔC’ for cue-referred) is distinct from the goal location indicated by the hippocampal map (ÔF’ for field-referred). The results show that
rats look for the goal at the field-referred location (i.e., their choices are based on the hippocampal map) only when they have to rely on a spatial
representation of the goal location (i.e., in the Far task), but not in other conditions (see text and [21] for details).
B. Poucet et al. / Journal of Physiology - Paris 97 (2003) 537–546
the cue was rotated to another fixed position in the
room, both the animal’s choice of maze arm and the
head direction cell’s preferred direction shifted in concert relative to the cue. However, on some infrequent
trials, the head direction cell’s preferred direction remained stable relative to background cues in spite of the
cue rotation. In these instances, it was observed that the
rat’s choice also stayed stable relative to the rotated cue,
thus remaining in register with the head direction signal.
Overall, these findings indicate that both place cells and
head direction cells play a role in guiding navigation.
4.2. Place cell activity in spatial and non-spatial navigation tasks
The cognitive map theory predicts that hippocampal
integrity is more critical for place navigation than for
orientation based on simpler mechanisms such as orienting to beacons. This hypothesis is supported by the
finding that hippocampal lesions disrupt place navigation
but not beacon navigation [35,41,45]. To address a similar issue at the place cell level, we looked at performance
by normal animals in place and beacon navigation tasks
after environmental manipulations that disturb the relationship between the place cell representation and the
cues used to solve the problems. The theory predicts that
such disturbances will disrupt performance of place
navigation but not of beacon navigation. To test this
prediction, rats were trained in several tasks that required
either map-based place navigation or simply heading
towards a strong marker stimulus [20].
We used the place preference paradigm developed by
Rossier et al. [50]. In this task, rats have to enter an
unmarked goal designated by the experimenter as the
goal, which then triggers release of a food reward from a
dispenser situated above the circular arena (Fig. 3B).
The rat then has to move away from the goal area to
retrieve the food pellet wherever it ended up in the
arena. The only spatial landmark is a salient white card
attached to the wall of the arena. Three distinct conditions were used with different rats. In the Far condition,
the goal was away from the wall card so that the rat had
to use a place strategy, i.e. to infer the goal location
from its spatial relationship with the card. In the Near
condition, the goal was located beneath the wall card so
that all the rat had to do was to move towards the card
(though it could use a place strategy as well). Finally, in
the Cue condition the goal was directly signaled by a
mark (a black disk) on the floor. The mark was moved
from one session to another (thus making the wall card
irrelevant for solving the task) so that the solution required a guidance strategy.
Place cells were recorded while rats performed the
task. To modify relationships between visible stimuli
and place cell activity, we made ‘‘hidden’’ or ‘‘visible’’
90° rotations of the card on the cylinder wall and, when
543
present, independent rotations of the disk on the cylinder floor. Hidden rotations were made with the rat removed from the cylinder and caused 90° firing field
rotations in a vast majority of sessions (>80%). Visible
rotations were made while the rat was inside the cylinder
and, as expected [53], caused 90° field rotations only in
minority of sessions (<30%). In the latter condition, the
failure of fields to rotate is caused by the conflict between motion-related and cue-related information that
is generated by the visible card rotations. More importantly, visible card rotations generally induced firing
fields to shift out of register with the new goal location
(as defined by the rotated card location) while hidden
card rotations generally induced firing fields to stay in
register with the new goal location.
In all conditions, each session started with a period
during which the feeder was switched off, irrespective of
the animal’s response. This partial extinction procedure
was used to let the animals search without any feedback
information about the goal location and thus allowed us
to determine where the rat ‘‘thought’’ the goal was located (Fig. 3C). The results of the different conditions
were contrasted. A strong decrease in performance was
observed in the Far condition when fields were out of
register with the card-referred goal. Most rats tended to
search for the goal in the field-referred rather than cardreferred goal location. In contrast, a modest decrease in
performance was observed in the Near condition when
fields were out of register with the card, with rats
searching for the goal at the card. Finally, field placements had no effect whatsoever on performance in the
Cue condition in which the goal was directly signaled by
a movable mark on the floor.
In summary, we found that visible rotations tended to
disrupt the relationship between firing fields and cues in
all tasks but impaired performance only in the spatial
problem that required map-based navigation. Thus, it
appears that the correct orientation of the hippocampal
map with the external stimuli is essential for efficient
performance in a navigational task but not in guidance
or beacon navigation tasks. Noticeably, reliable place
cell firing was observed in all tasks, i.e., whether or not
the rat had a spatial navigation task to accomplish (see
also [61]). Therefore, place cells continuously provide
background information as to the rat’s location, yet this
information appears critical only for true spatial navigation. We therefore conclude, as proposed by the
spatial theory of hippocampal function that the rodent
hippocampus participates in solutions of place navigation tasks but not of simpler guidance tasks.
5. Conclusion
This review addressed issues about the cortical origin
of the place cell firing patterns and about the functional
544
B. Poucet et al. / Journal of Physiology - Paris 97 (2003) 537–546
significance of place cell activity. As to the first of these
two issues, several cortical areas appear to subserve
complementary functions in the generation of place cell
firing. For example, the perirhinal cortex is required for
long-term stability of firing fields [37]. The retrosplenial
cortex appears to be important for the initial processing
of spatial cues but would also be needed for the mnemonic use of these cues to guide navigation when they
have been removed [33]. In contrast, the visual, parietal
and entorhinal cortices appear to be involved in the
selection of cues necessary for the spatial anchoring of
firing fields; the three areas seem to process separate
aspects of space, with the entorhinal cortex being more
involved in processing distal cues [30,46], the visual and
parietal cortices dealing with the local aspects of the
environment explored by the rat [47]. Although this
description is schematic, it has the advantage of providing a framework within which more refined functions can be worked out. It seems to us, however, that
such refinement will require more standardized procedures for recording place cell activity among different
laboratories.
With regard to the issue of the functional significance
of place cell activity, we provided strong evidence
that place cell signals are crucial when the animal
needs to ‘‘know’’ its own position and the positions
of other objects. An important issue, however, is whether place cells directly guide navigation, or are just
one component in a larger network of structures more
actively involved. In the latter and more likely view,
the network would probably have to include not only
brain areas in which head direction cells were found [60],
but also areas known to be involved in behavioral
decisions in an essential way (e.g., prefrontal and parietal cortex).
Another difficulty with the correlational approach
that underlies our research is that it does not reveal what
hippocampal cell firing patterns would signal in nonspatial complex tasks. Thus, it is difficult to determine
the generality of this conclusion. In particular, it is
known that hippocampal cells have behavioral correlates in non-spatial tasks, therefore suggesting that the
hippocampus is involved in the processing of both spatial and non-spatial relational information [8,63]. Yet
the specificity of the hippocampal place cell signal, as
well as the properties of head direction cells and the
strong coupling that seems to exist between the two
populations of cells [18], make it very likely that an
important function of this system is to process spatial
information for navigation.
Acknowledgements
Support for this work was provided by the CNRS
and the MENRT. We thank A. Cressant and R. Muller
for their contribution to some of the experimental work
reported herein, Bill MacKay for checking the English,
and two anonymous reviewers for useful comments on a
previous version.
References
[1] R.D. Burwell, D.G. Amaral, Cortical afferents of the perirhinal,
postrhinal, and entorhinal cortices of the rat, J. Comp. Neurol.
398 (1998) 179–205.
[2] R.D. Burwell, M.P. Witter, D.G. Amaral, Perirhinal and postrhinal cortices of the rat: a review of the neuroanatomical literature
and comparison with findings from the monkey brain, Hippocampus 5 (1995) 390–408.
[3] J. Cho, P.E. Sharp, Head direction, place, and movements
correlates for cells in the rat retrosplenial cortex, Behav. Neurosci.
115 (2001) 3–25.
[4] Y.H. Cho, K.P. Giese, H.T. Tanila, A.J. Silva, H. Eichenbaum,
Abnormal hippocampal spatial representations in aCaMKIIT286A
and CREBaD -mice, Science 279 (1998) 867–869.
[5] A. Cressant, R.U. Muller, B. Poucet, Failure of centrally placed
objects to control the firing fields of hippocampal place cells,
J. Neurosci. 17 (1997) 2531–2542.
[6] B.G. Cooper, S.J.Y. Mizumori, Temporary inactivation of
the retrosplenial cortex causes a transient reorganization of
spatial coding in the hippocampus, J. Neurosci. 21 (2001) 3986–
4001.
[7] P. Dudchenko, J.S. Taube, Correlation between head direction
cell activity and spatial behavior on a radial maze, Behav.
Neurosci. 111 (1997) 3–19.
[8] H. Eichenbaum, T. Otto, N.J. Cohen, The hippocampus: what
does it do? Behav. Neur. Biol. 57 (1992) 2–36.
[9] A.S. Etienne, R. Maurer, V. Seguinot, Path integration in
mammals and its interaction with visual landmarks, J. Exp. Biol.
119 (1996) 201–209.
[10] N. Foreman, R. Stevens, Visual lesions and radial maze performance in rats, Behav. Neur. Biol. 16 (1982) 126–136.
[11] S.E. Fox, J.B. Ranck Jr., Electrophysiological characteristics of
hippocampal complex-spike cells and theta cells, Exp. Brain Res.
41 (1981) 399–410.
[12] M.A. Goodale, R.H.I. Dale, Radial-maze performance in the rat
following lesions of posterior neocortex, Behav. Brain Res. 3
(1981) 273–288.
[13] K.M. Gothard, W.E. Skaggs, B.L. McNaughton, Dynamics of
mismatch correction in the hippocampal ensemble code for space:
interaction between path integration and environmental cues,
J. Neurosci. 16 (1996) 8027–8040.
[14] K.T. Harker, I.Q. Whishaw, Impaired spatial performance in rats
with retrosplenial lesions: importance of the spatial problem and
the rat strain in identifying lesion effects in a swimming pool,
J. Neurosci. 22 (2002) 1155–1164.
[15] B. Hill, P. Best, Effects of deafness and blindness on the spatial
correlates of hippocampal unit activity in the rat, Exp. Neurol. 74
(1981) 204–217.
[16] L.E. Jarrard, Selective hippocampal lesions and behavior: effects
of kainic acid lesions on performance of place and cue tasks,
Behav. Neurosci. 97 (1983) 873–889.
[17] C. Kentros, E. Hargreaves, R.D. Hawkins, E.R. Kandel, M.
Shapiro, R.U. Muller, Abolition of long-term stability of new
hippocampal place cell maps by NMDA receptor blockade,
Science 280 (1998) 2121–2126.
[18] J.J. Knierim, H.S. Kudrimoti, B.L. McNaughton, Place cells,
head direction cells, and the learning of landmark stability,
J. Neurosci. 15 (1995) 1648–1659.
B. Poucet et al. / Journal of Physiology - Paris 97 (2003) 537–546
[19] W.J.S. Krieg, Connections of the cerebral cortex: I. The albino
rat: a. topography of the cortical areas, J. Comp. Neurol. 84
(1946) 221–275.
[20] P.P. Lenck-Santini, R.U. Muller, E. Save, B. Poucet, Relationships between place cell firing fields and navigational decisions by
rats, J. Neurosci. 22 (2002) 9035–9047.
[21] P.P. Lenck-Santini, E. Save, B. Poucet, Evidence for a relationship
between the firing patterns of hippocampal place cells and rat’s
performance in a spatial memory task, Hippocampus 11 (2001)
377–390.
[22] M.D. Lindner, M.A. Plone, T. Schallert, D.F. Emerich, Blind rats
are not profoundly impaired in the reference memory Morris
water maze and cannot be clearly discriminated from rats with
cognitive deficits in the cued platform task, Cognit. Brain Res. 5
(1997) 329–333.
[23] P. Liu, D.K. Bilkey, Lesions of perirhinal cortex produce spatial
memory deficits in the radial maze, Hippocampus 8 (1998) 114–
121.
[24] P. Liu, D.K. Bilkey, Perirhinal cortex contributions to performance in the Morris water maze, Behav. Neurosci. 112 (1998)
304–315.
[25] P. Liu, D.K. Bilkey, Excitotoxic lesions centred on perirhinal
cortex produce delay-dependent deficits in a test of spatial memory, Behav. Neurosci. 112 (1998) 512–524.
[26] W.F. McDaniel, R.G. Brown, Radial maze performance following
restricted posterior neocortical lesions, IRCS Med. Sci. 12 (1984)
807–808.
[27] T.J. McHugh, K.I. Blum, J.Z. Tsien, S. Tonegawa, M.A. Wilson,
Impaired hippocampal representation of space in CA1-specific
NMDAR1 knockout mice, Cell 87 (1996) 1339–1349.
[28] B.L. McNaughton, C.A. Barnes, J.L. Gerrard, K. Gothard, M.W.
Jung, J.J. Knierim, H. Kudrimoti, Y. Qin, W.E. Skaggs, M.
Suster, K.L. Weaver, Deciphering the hippocampal polyglot: the
hippocampus as a path integration system, J. Exp. Biol. 119 (1996)
173–185.
[29] B.L. McNaughton, L.L. Chen, E.J. Markus, ‘‘Dead reckoning’’,
landmark learning, and the sense of direction: a neurophysiological and computational hypothesis, J. Cognit. Neurosci. 3 (1991)
190–202.
[30] V.M. Miller, P.J. Best, Spatial correlates of hippocampal unit
activity are altered by lesions of the fornix and entorhinal cortex,
Brain Res. 194 (1980) 311–323.
[31] H. Mittelsteadt, The role of multimodal convergence in homing by
path integration, Fortschritte der Zoologie 28 (1983) 197–212.
[32] M.L. Mittelsteadt, H. Mittelsteadt, Homing by path integration in
a mammal, Naturwissenschaften 67 (1980) 566–567.
[33] S.J.Y. Mizumori, B.G. Cooper, S. Leutgeb, W.E. Pratt, A neural
system analysis of adaptive navigation, Mol. Neurobiol. 21 (2001)
57–82.
[34] R.G.M. Morris, E. Anderson, G.G. Lynch, M. Baudry, Selective
impairment of learning and blockade of long-term potentiation
by an N-methyl-D -aspartate receptor antagonist, AP5, Nature
319 (1986) 774–776.
[35] R.G.M. Morris, J.J. Hagan, J.N.P. Rawlins, Allocentric spatial
learning by hippocampectomised rats: a further test of the ‘‘spatial
mapping’’ and ‘‘working memory’’ theories of hippocampal
function, Q, J. Exp. Psychol. B 38 (1986) 365–395.
[36] R.G.M. Morris, F. Schenk, F. Tweedie, L.E. Jarrard, Ibotenate
lesions of hippocampus and/or subiculum: dissociating components of allocentric spatial learning, Eur. J. Neurosci. 2 (1990)
1016–1028.
[37] G.M. Muir, D.K. Bilkey, Instability in the place field location of
hippocampal place cells after lesions centered on the perirhinal
cortex, J. Neurosci. 21 (2001) 4016–4025.
[38] R.U. Muller, J.L. Kubie, The effects of changes in the environment on the spatial firing of hippocampal complex-spike cells,
J. Neurosci. 7 (1987) 1951–1968.
545
[39] R.U. Muller, E.M. Bostock, J.S. Taube, J.L. Kubie, On the
directional firing properties of hippocampal place cells, J. Neurosci. 14 (1994) 7235–7251.
[40] J. O’Keefe, Place units in the hippocampus of the freely moving
rat, Exp. Neurol. 51 (1976) 78–109.
[41] J. O’Keefe, D.H. Conway, On the trail of the hippocampal
engram, Physiol. Psychol. 8 (1980) 229–238.
[42] J. O’Keefe, J. Dostrovsky, The hippocampus as a spatial map.
Preliminary evidence from unit activity in the freely moving rat,
Brain Res. 34 (1971) 171–175.
[43] J. O’Keefe, L. Nadel, The Hippocampus as a Cognitive Map,
Clarendon, Oxford, 1978.
[44] J. O’Keefe, A. Speakman, Single unit activity in the rat hippocampus during a spatial memory task, Exp. Brain Res. 68 (1987)
1–27.
[45] M.G. Packard, J.L. McGaugh, Inactivation of hippocampus and
caudate nucleus with lidocaine differentially affects expression of
place and response learning, Neurobiol. Learn. Mem. 65 (1996)
65–72.
[46] C. Parron, B. Poucet, E. Save, Entorhinal cortex lesions in rats
impair the use of distal landmarks but not of proximal landmarks
during navigation, Behav. Pharmacol. 12 (2001) S75.
[47] V. Paz-Villagran, P.P. Lenck-Santini, E. Save, B. Poucet, Properties of place cell firing after damage to the visual cortex, Eur. J.
Neurosci. 16 (2002) 771–776.
[48] B. Poucet, E. Save, P.P. Lenck-Santini, Sensory and memory
properties of place cells firing, Rev. Neurosci. 11 (2000) 95–111.
[49] G.J. Quirk, R.U. Muller, J.L. Kubie, The firing of hippocampal
place cells in the dark depends on the rat’s recent experience,
J. Neurosci. 10 (1990) 2008–2017.
[50] J. Rossier, F. Schenk, Y. Kaminsky, J. Bures, The place
preference task: a new tool for studying the relation between
behavior and place cell activity in rats, Behav. Neurosci. 114
(2000) 273–284.
[51] A. Rotenberg, T. Abel, R.D. Hawkins, E.R. Kandel, R.U. Muller,
Parallel instabilities of long-term potentiation, place cells, and
learning caused by decreased protein kinase A activity, J. Neurosci. 20 (2000) 8096–8102.
[52] A. Rotenberg, M. Mayford, R.D. Hawkins, E.R. Kandel, R.U.
Muller, Mice expressing activated CaMKII lack low frequency
LTP and do not form stable place cells in the CA1 region of the
hippocampus, Cell 87 (1996) 1351–1361.
[53] A. Rotenberg, R.U. Muller, Variable place-cell coupling to a
continuous viewed stimulus: evidence that the hippocampus acts
as a perceptual system, Phil. Trans. Roy. Soc. (London B) 352
(1997) 1505–1513.
[54] E. Save, M.-C. Buhot, N. Foreman, C. Thinus-Blanc, Exploratory
activity and response to a spatial change in rats with hippocampal
or posterior parietal cortical lesions, Behav. Brain Res. 47 (1992)
113–127.
[55] E. Save, A. Cressant, C. Thinus-Blanc, B. Poucet, Spatial firing of
hippocampal place cells in blind rats, J. Neurosci. 18 (1998) 1818–
1826.
[56] E. Save, L. Nerad, B. Poucet, Contribution of multiple sensory
information to place field stability in hippocampal place cells,
Hippocampus 10 (2000) 64–76.
[57] E. Save, B. Poucet, Hippocampal-parietal cortical interactions in
spatial cognition, Hippocampus 10 (2000) 491–499.
[58] P.E. Sharp, H.T. Blair, D. Etkin, D.B. Tzanetos, Influences of
vestibular and visual motion information on the spatial firing
patterns of hippocampal place cells, J. Neurosci. 15 (1995) 173–
189.
[59] C.J. Shi, M.D. Cassell, Perirhinal cortex projections to the
amygdaloid complex and hippocampal formation in the rat,
J. Comp. Neurol. 406 (1999) 299–328.
[60] J.S. Taube, Head direction cells and the neurophysiological basis
for a sense of direction, Prog. Neurobiol. 55 (1998) 225–256.
546
B. Poucet et al. / Journal of Physiology - Paris 97 (2003) 537–546
[61] O. Trullier, R. Shibata, A.B. Mulder, S.I. Wiener, Hippocampal
neuronal position selectively remains fixed to room cues only in
rats alternating between place navigation and beacon approach
tasks, Eur. J. Neurosci. 11 (1999) 4381–4388.
[62] M.P. Witter, Organization of the entorhinal-hippocampal system:
a review of current anatomical data, Hippocampus 3 (1993) 33–44.
[63] E.R. Wood, P.A. Dudchenko, H. Eichenbaum, The global record
of memory in hippocampal neuronal activity, Nature 397 (1999)
613–616.
[64] J.M. Wyss, T. van Groen, Connections between the retrosplenial
cortex and the hippocampal formation in the rat: a review,
Hippocampus 2 (1992) 1–12.