The Hippocampus, Memory, and Place Cells
Authors: Howard Eichenbaum, Paul Dudchenko, Emma Wood, Matthew Shapiro, Heikki Tanila
Journal: Neuron (1999)

Identifying the scope and nature of memory processing by the hippocampus has proved a formidable challenge. The major initial insights came from studies of amnesia in human patients following removal of the hippocampus plus neighboring medial temporal structures (105Scoville W.B Milner B Loss of recent memory after bilateral hippocampal lesions.J. Neurol. Neurosurg. Psychiatry. 1957; 20: 11-12Crossref PubMed Scopus (3810) Google Scholar). The early studies indicated that this damage spares the initial acquisition of new information, but memory for all sorts of new information subsequently declines rapidly. More recent studies have shown that global amnesia results from limited damage within the hippocampus itself (140Zola-Morgan S.M Squire L.R Amaral D.G Human amnesia and the medial temporal region enduring memory impairment following a bilateral lesion limited to field CA1 of the hippocampus.J. Neurosci. 1986; 6: 2950-2967PubMed Google Scholar) or including the hippocampus and dentate gyrus and sparing most or all of the surrounding cortex and other medial temporal structures (127Vargha-Khadem F Gadian D.G Watkins K.E Connelly A Van Paesschen W Mishkin M Differential effects of early hippocampal pathology on episodic and semantic memory.Science. 1997; 277: 376-380Crossref PubMed Scopus (1134) Google Scholar). These findings indicate that the hippocampus plays a critical role in memory formation for a broad domain of information in humans. Many studies have sought to clarify the nature of hippocampal information processing, using neuropsychological and electrophysiological approaches in animals. Among several proposals generated by these studies, one that has captured considerable attention is the view that the hippocampus mediates a neural representation of physical space, that is, a cognitive map (80O'Keefe J.A Nadel L The Hippocampus as a Cognitive Map. Oxford University Press, New York1978Google Scholar). This theory was based on a thorough and systematic analysis of the expansive literature on diverse behavioral abnormalities following hippocampal damage. In addition, O'Keefe and Nadel's proposal incorporated a central observation about the behavioral physiology of hippocampal neurons, specifically that some cells increased firing rate when a rat was at a particular location in its environment (79O'Keefe J Dostrovsky J The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat.Brain Res. 1971; 34: 171-175Crossref PubMed Scopus (2572) Google Scholar). The discovery of these place cells appeared to perfectly complement the findings on the behavioral deficits, showing that spatial information was encoded within the cellular activity of the very hippocampal structures that are necessary for spatial learning and memory. Despite its appeal, the cognitive mapping theory, and in particular the findings on place cells, have had limited impact among neuropsychologists who study memory in humans and nonhuman primates. A major source of this limitation has been the contention that hippocampal processing is dedicated to spatial memory in rodents, in contrast to the global memory deficits observed following damage to the hippocampal region in humans and more recently in animals as well (21Eichenbaum H Declarative memory insights from cognitive neurobiology.Annu. Rev. Psychol. 1997; 48: 547-572Crossref PubMed Scopus (229) Google Scholar). Furthermore, several recent electrophysiological studies have revealed properties of hippocampal neuronal firing patterns that are inconsistent with the notion of a cognitive map and indicate a broader scope of information processing. This paper will focus on these studies, reviewing some of the history and basic properties of place cells, and considering both early and recent findings that shed light on the content and organization of information encoded within hippocampal neuronal activity. We will call into question the cognitive map account and offer an alternative view. In the early years of investigations on animal learning, proponents of the dominant "stimulus–response" ("S–R") theory argued that maze learning is mediated by a chain of direct associations between specific stimuli and rewarded behavioral responses. However, Edward 125Tolman E.C Cognitive maps in rats and men.Psychol. Rev. 1948; 55: 189-208Crossref PubMed Scopus (2385) Google Scholar provided compelling evidence that rats can navigate mazes using short cuts and roundabout routes to find goal locations, strategies that were not readily explained by S–R theory. Tolman concluded that rats create and use global representations of the environment, that is, cognitive maps, to localize goals in a maze. This view was criticized for the absence of evidence for a cognitive or neural mechanism that could underlie the cognitive map—something as compelling as the physiological observations on the conditioned reflexes that were viewed to mediate S–R learning. In the initial report on the discovery of place cells79O'Keefe J Dostrovsky J The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat.Brain Res. 1971; 34: 171-175Crossref PubMed Scopus (2572) Google Scholar recognized the potential significance of this neural correlate. Could these cells be the elements of the long sought, and much maligned, cognitive map? Hippocampal place cells are fascinating to anyone who has witnessed the phenomenon. They are typically observed by monitoring extracellularly recorded action potentials from principal cells in CA1 and CA3 of freely behaving rats (28Fox S.E Ranck Jr., J.B Localization and anatomical identification of theta and complex spike cells in dorsal hippocampal formation of rats.Exp. Neurol. 1975; 49: 299-313Crossref PubMed Scopus (169) Google Scholar). As the animal engages in behaviors across a large environment, one can readily correlate dramatic increases in a place cell's firing rate when the rat arrives at a particular location, called the "place field." From a baseline of <1 spike/s, the firing rate can exceed 100 Hz, although during some passes though the place field the cell may not fire at all. Typically, a large fraction of cells have place fields in any environment (66Muller R.U A quarter of a century of place cells.Neuron. 1996; 17: 813-822Abstract Full Text Full Text PDF PubMed Scopus (246) Google Scholar, 112Shen J Barnes C.A McNaughton B.L Skaggs W.E Weaver K.L The effect of aging on experience-dependent plasticity of hippocampal place cells.J. Neurosci. 1997; 17: 6769-6782Crossref PubMed Google Scholar, 120Tanila H Shapiro M Gallagher M Eichenbaum H Brain aging impaired coding of novel environmental cues.J. Neurosci. 1997; 17 (a): 5167-5174PubMed Google Scholar), although the low baseline firing rates may let many cells without place fields go undetected (123Thompson L.T Best P.J Place cells and silent cells in the hippocampus of freely-behaving rats.J. Neurosci. 1989; 9: 2382-2390Crossref PubMed Google Scholar). Place responses can be dissociated from potential confounding influences of particular behaviors that might occur at different locations. 84Olton D.S Branch M Best P.J Spatial correlates of hippocampal unit activity.Exp. Neurol. 1978; 58: 387-409Crossref PubMed Scopus (194) Google Scholar observed hippocampal cellular activity in rats performing the same inward and outward traversals on all arms of a radial maze, and they found that many hippocampal cells fired only when the rat was on a particular arm (see also 59McNaughton B.L Barnes C.A O'Keefe J The contributions of position, direction, and velocity to single unit activity in the hippocampus of freely-moving rats.Exp. Brain Res. 1983; 52: 41-49Crossref PubMed Scopus (577) Google Scholar; Figure 1A). 68Muller R.U Kubie J.L Ranck Jr., J.B Spatial firing patterns of hippocampal complex spike cells in a fixed environment.J. Neurosci. 1987; 7: 1935-1950PubMed Google Scholar more completely equalized behavior throughout an environment by observing hippocampal cellular activity in rats foraging for food pellets randomly dispersed in a circular open field (Figure 1B) and found location-specific activity of many of the cells. Furthermore, the activity of many place cells is not dependent on any particular stimulus but rather reflects the presence and topography of multiple environmental cues. 78O'Keefe J.A Conway D.H Hippocampal place units in the freely moving rat why they fire when they fire.Exp. Brain Res. 1978; 31: 573-590Crossref PubMed Scopus (558) Google Scholar observed the responses of hippocampal cells to cue manipulations in rats performing a place discrimination on the elevated plus maze (Figure 1C). They found that many place cells maintained their spatial firing patterns when any one or two of the cues were removed, and they concluded that any subset of the cues sufficient to define their global configuration could support the location-specific activity. 67Muller R.U Kubie J.L The effects of changes in the environment on the spatial firing of hippocampal complex-spike cells.J. Neurosci. 1987; 7: 1951-1968Crossref PubMed Google Scholar found that expansion of their circular open field caused some place fields to "scale up" in size but maintain the same shape and location, whereas altering the shape of the environment resulted in loss or unpredictable changes in spatial firing patterns. 77O'Keefe J Burgess N Geometric determinants of the place fields of hippocampal neurons.Nature. 1996; 381: 425-428Crossref PubMed Scopus (616) Google Scholar showed that the shape and locus of place fields within a simple rectangular chamber are determined by the dimensions of, and spatial relations between, the walls of the environment. Each of these studies indicates that some hippocampal place cells encode cues about the topology of environments (see also 18Cressant A Muller R.U Poucet B Failure of centrally placed objects to control the firing fields of hippocampal place cells.J. Neurosci. 1997; 17: 2531-2542Crossref PubMed Google Scholar). Additional properties of place cells are consistent with features of spatial memory. Once established, place cells can have the same firing pattern for months (124Thompson L.T Best P.J Long-term stability of place-field activity of single units recorded from the dorsal hippocampus of freely behaving rats.Brain Res. 1990; 509: 299-308Crossref PubMed Scopus (224) Google Scholar). The firing patterns can persist even when all of the spatial cues are removed or the room is darkened (67Muller R.U Kubie J.L The effects of changes in the environment on the spatial firing of hippocampal complex-spike cells.J. Neurosci. 1987; 7: 1951-1968Crossref PubMed Google Scholar, 81O'Keefe J.A Speakman A Single unit activity in the rat hippocampus during a spatial memory task.Exp. Brain Res. 1987; 68: 1-27Crossref PubMed Scopus (486) Google Scholar, 90Quirk G.J Muller R.U Kubie J.L The firing of hippocampal place cells in the dark depends on the rat's recent experience.J. Neurosci. 1990; 10: 2008-2017Crossref PubMed Google Scholar), although the selectivity of spatial firing may be degraded in the dark (52Markus E.J Barnes C.A McNaughton B.L Gladden V.L Skaggs W.E Spatial information content and reliability of hippocampal CA1 neurons effects of visual input.Hippocampus. 1994; 4: 410-421Crossref PubMed Scopus (198) Google Scholar). In an experiment where rats had to remember where removed spatial cues had been, errors in their choice behavior predicted shifts of their hippocampal place fields, suggesting that these codings were determined by the orientation of the maze remembered by the rat (81O'Keefe J.A Speakman A Single unit activity in the rat hippocampus during a spatial memory task.Exp. Brain Res. 1987; 68: 1-27Crossref PubMed Scopus (486) Google Scholar). These findings provide a compelling link between hippocampal spatial coding and spatial memory. All of these findings are consistent with 80O'Keefe J.A Nadel L The Hippocampus as a Cognitive Map. Oxford University Press, New York1978Google Scholar notion of place cells as elements of a cognitive map that resides in the hippocampus. Consistent with 125Tolman E.C Cognitive maps in rats and men.Psychol. Rev. 1948; 55: 189-208Crossref PubMed Scopus (2385) Google Scholar description of a "cognitive-like map of the environment" (p. 192), the conception common to 75O'Keefe J.A A review of hippocampal place cells.Prog. Neurobiol. 1979; 13: 419-439Crossref PubMed Scopus (327) Google Scholar characterization and to all modern accounts of the cognitive map is that the hippocampus contains a holistic representation of space (66Muller R.U A quarter of a century of place cells.Neuron. 1996; 17: 813-822Abstract Full Text Full Text PDF PubMed Scopus (246) Google Scholar), a facsimile of the environment including the salient environmental cues (Figure 2). This map constitutes an abstract coordinate grid of two-dimensional space, instantiated by a preconfigured network of intrinsic connections among hippocampal neurons (80O'Keefe J.A Nadel L The Hippocampus as a Cognitive Map. Oxford University Press, New York1978Google Scholar, 61McNaughton B.L Barnes C.A Gerrard J.L Gothard K Jung M.W Knierim J.J Kudrimoti H Qin Y Skagges W.E Suster M Weaver K.L Deciphering the hippocampal polyglot the hippocampus as a path integration system.J. Exp. Biol. 1996; 199: 173-185PubMed Google Scholar, 104Samsonovich A McNaughton B Path integration and cognitive mapping in a continuous attractor neural network model.J. Neurosci. 1997; 17: 5900-5920Crossref PubMed Google Scholar). The resulting map is Cartesian in that it provides metrics for the representation of distances and angles between the relevant stimuli. At the physiological level, a place cell reflects the occurrence of the rat at a particular coordinate position within the map. Thus, implicit in this model is the assumption that place fields can be considered "pointers" within a unified map. Finally, it should be clear that all models of the cognitive map involve exclusively allocentric spatial frameworks, that is, representations of space independent of the egocentric spatial information such as the animal's direction of movement. Observations of, for example, direction-selective spatial activity are considered an artifact of confusing multiple allocentric maps (61McNaughton B.L Barnes C.A Gerrard J.L Gothard K Jung M.W Knierim J.J Kudrimoti H Qin Y Skagges W.E Suster M Weaver K.L Deciphering the hippocampal polyglot the hippocampus as a path integration system.J. Exp. Biol. 1996; 199: 173-185PubMed Google Scholar) or simply a result of different predictions about future location in the map depending on the direction of movement (77O'Keefe J Burgess N Geometric determinants of the place fields of hippocampal neurons.Nature. 1996; 381: 425-428Crossref PubMed Scopus (616) Google Scholar). Details about the nature of the hippocampal spatial map have been modified in several recent models, and several mechanisms for its implementation have been offered. 136Worden R Navigation by fragment fitting a theory of hippocampal function.Hippocampus. 1992; 2: 165-188Crossref PubMed Scopus (75) Google Scholar proposed that the hippocampus fits codings of "fragments" of the environment into a cohesive representation of the environment. McNaughton and colleagues (61McNaughton B.L Barnes C.A Gerrard J.L Gothard K Jung M.W Knierim J.J Kudrimoti H Qin Y Skagges W.E Suster M Weaver K.L Deciphering the hippocampal polyglot the hippocampus as a path integration system.J. Exp. Biol. 1996; 199: 173-185PubMed Google Scholar, 104Samsonovich A McNaughton B Path integration and cognitive mapping in a continuous attractor neural network model.J. Neurosci. 1997; 17: 5900-5920Crossref PubMed Google Scholar) suggested that the metric for the map is self-motion. They and others (93Redish A.D Touretzky D.S Cognitive maps beyond the hippocampus.Hippocampus. 1997; 7: 15-35Crossref PubMed Scopus (218) Google Scholar) have suggested that during learning, representations of visual cues are bound to "charts" and serve as landmarks of a spatial reference frame for path integration. 76O'Keefe J.A An allocentric spatial model for the hippocampal cognitive map.Hippocampus. 1991; 1: 230-235Crossref PubMed Scopus (64) Google Scholar suggested that a polar coordinate system may be most effective for translating egocentric coordinates into an allocentric reference frame. More recently14Burgess N O'Keefe J Neuronal computations underlying the firing of place cells and their role in navigation.Hippocampus. 1996; 7: 749-762Crossref Scopus (130) Google Scholar suggested a population vector model for navigation. O'Keefe and Burgess (1997) built a model of place representations based on distances from the walls of an environment. 8Blum K.I Abbott L.F A model of spatial map formation in the hippocampus of the rat.Neural Comput. 1995; 8: 85-93Crossref Scopus (227) Google Scholar proposed that intrinsic synaptic connections between place cells representing sequentially visited locations are asymmetrically potentiated during repeated motions, supporting the learning of paths. 70Muller R.U Stead M Pach J The hippocampus as a cognitive graph.J. Gen. Physiol. 1996; 107: 663-694Crossref PubMed Scopus (193) Google Scholar conceived that distances in a hippocampal "cognitive graph" are encoded according to distributions of synaptic strengths that arise through the differential timing of activations between place cells. Summing up all these current models, several new proposals about the metrics and mechanisms of mapping and navigational computations have been generated since O'Keefe and Nadel's original proposal. However, the central features of the hippocampal cognitive (spatial) map remain fundamentally intact. Within all these accounts, cognitive maps involve a systematic, cohesive, allocentric coordinate framework into which environmental features are encoded (Figure 2). The dedicated function of this system is to determine an animal's location and to mediate navigational computations. The existence of location-specific activity of hippocampal neurons has been confirmed many times (see 75O'Keefe J.A A review of hippocampal place cells.Prog. Neurobiol. 1979; 13: 419-439Crossref PubMed Scopus (327) Google Scholar, 66Muller R.U A quarter of a century of place cells.Neuron. 1996; 17: 813-822Abstract Full Text Full Text PDF PubMed Scopus (246) Google Scholar). However, as we will argue here, the evidence falls short of demonstrating that place cells are organized as a spatial map or that hippocampal neurons exclusively, or even primarily, encode spatial cues. 64Morris R.G.M Does the hippocampus play a disproportionate role in spatial memory?.Disc. Neurosci. VI. 1990; 39–45Google Scholar pointed out that one major problem with the cognitive map view is the absence of evidence indicating how place cells that reflect only one's current location would guide movements to other important places. There are additional fundamental problems with the notion of place cells composing a map. Consider two central features of mapping illustrated in Figure 2. Systematic spatial maps are characterized by continuous and homogeneous representations of spatial loci, and these representations are bound together within a unified Cartesian framework. Evidence of these properties would provide a strong case for the cognitive map model. Yet, despite considerable effort, the evidence disconfirms rather than supports these properties. Identifying one's location throughout the environment requires that the entire space be represented, and most simply would be represented by a set of place fields distributed uniformly throughout the environment. Demonstration of a continuous and homogeneous representation of space onto hippocampal structure would provide compelling evidence for a fundamental spatial mapping function. However, even from the earliest studies, it was apparent that space is not represented this way within the hippocampus. Place fields are not continuously or topographically organized; instead, there is substantial evidence for a "clustering" of place fields of neighboring cells (24Eichenbaum H Wiener S.I Shapiro M Cohen N.J The organization of spatial coding in the hippocampus a study of neuronal ensemble activity.J. Neurosci. 1989; 10: 331-339Google Scholar, 37Hampson R.E Byrd D.R Konstantopoulos J.K Bunn T Deadwyler S.A Hippocampal place fields relationship between degree of field overlap and cross-correlations within ensembles of hippocampal neurons.Hippocampus. 1996; 6: 281-293Crossref PubMed Scopus (26) Google Scholar), similar to the observation of clustered, nontopographic perceptual representations of complex visual properties in the inferotemporal cortex (89Perret D.I Mistlin A.J Chitty A.J Visual cells responsive to faces.Trends Neurosci. 1987; 10: 358-364Abstract Full Text PDF Scopus (252) Google Scholar, 118Tanaka K Saito H Fukada Y Moriya M Coding visual images of objects in the inferotemporal cortex of the macaque monkey.J. Neurosci. 1991; 6: 134-144Google Scholar) and egocentric information in prefrontal and parietal associations areas (30Funahashi S Bruce C.J Goldman-Rakic P.S Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex.J. Neurophysiol. 1989; 61: 331-349Crossref PubMed Scopus (0) Google Scholar, 119Tanila H Carlson S Linnankoski I Kahila H Regional distribution of functions in dorsolateral prefrontal cortex of the monkey.Behav. Brain Res. 1993; 53: 63-71Crossref PubMed Scopus (34) Google Scholar; Andersen, 1995). In addition41Hetherington P.A Shapiro M.L Hippocampal place fields are altered by the removal of single visual cues in a distance-dependent manner.Behav. Neurosci. 1997; 111: 20-34Crossref PubMed Scopus (97) Google Scholar observed hippocampal firing patterns in rats exploring an enclosed environment with a different prominent cue on each wall. They found that place fields systematically concentrated near the wall cues, rather than areas that lack predominant local stimuli. Furthermore, the place fields were more strongly controlled by a proximal cue, consistent with 77O'Keefe J Burgess N Geometric determinants of the place fields of hippocampal neurons.Nature. 1996; 381: 425-428Crossref PubMed Scopus (616) Google Scholar findings and indicating that a critical aspect of spatial firing is the distance from neighboring stimuli. These observations indicate that hippocampal representation does not involve a homogeneous representation of all the areas of physical space. If hippocampal activity reflects occupancy of a coordinate position within a systematic map, all place cells should encode position within the global topology of the environment, and these codings should be bound to one another within a holistic, cohesive spatial framework. However, several recent findings are inconsistent with these expectations, and instead the data indicate that hippocampal spatial firing patterns reflect independent representations of subsets of the spatial cues. For example, in 67Muller R.U Kubie J.L The effects of changes in the environment on the spatial firing of hippocampal complex-spike cells.J. Neurosci. 1987; 7: 1951-1968Crossref PubMed Google Scholar experiment (see above), the majority of cells lost or changed their place fields when the environment was expanded. In 77O'Keefe J Burgess N Geometric determinants of the place fields of hippocampal neurons.Nature. 1996; 381: 425-428Crossref PubMed Scopus (616) Google Scholar study, most of the place fields reflected distances from the closest walls, and none had the same place field in two boxes with the same shape but different size and a different firing pattern in two boxes of another shape. These findings indicate that overall topology was not the major influence for most cells in either of these studies. Several recent studies have shown that place cells can encode subsets of the spatial cues and that these representations are not bound to other spatial representations in the same environment. 33Gothard K.M Skaggs W.E Moore K.M McNaughton B.L Binding of hippocampal CA1 neural activity to multiple reference frames in a landmark-based navigation task.J. Neurosci. 1996; 16 (a): 823-835Crossref PubMed Google Scholar, 34Gothard K.M Skaggs W.E McNaughton B.L Dynamics of mismatch correction in the hippocampal ensemble code for space interaction between path integration and environmental cues.J. Neurosci. 1996; 16 (b): 8027-8040PubMed Google Scholar found that when a particularly salient cue or enclosure within an open field is moved repeatedly and randomly, the spatial firing patterns of some cells become tied to that cue. When rats were trained to shuttle between a mobile starting box and a goal location defined by landmarks in an open field, some cells fired relative to the static environmental cues, but others fired relative to a landmark-defined goal site or in relation to the start box. When rats were trained to shuttle between a movable start-end box and goal site on a linear track, the anchor of the spatial representation of many cells switched between these two cues, depending on which was closer. Under these conditions, the majority of the activated hippocampal cells did not exhibit location-specific activity that was associated with fixed environmental cues. Instead, their activity could be characterized as "spatial" only to the extent that they fired at specific distances from a particular stimulus or goal. Shapiro, Tanila, and colleagues (109Shapiro M.L Tanila H Eichenbaum H Cues that hippocampal place cells encode dynamic and hierarchical representation of local and distal stimuli.Hippocampus. 1997; 7: 624-642Crossref PubMed Scopus (204) Google Scholar, 120Tanila H Shapiro M Gallagher M Eichenbaum H Brain aging impaired coding of novel environmental cues.J. Neurosci. 1997; 17 (a): 5167-5174PubMed Google Scholar, 122Tanila H Sipila P Shapiro M Eichenbaum H Brain aging changes in the nature of information coding by the hippocampus.J. Neurosci. 1997; 17 (c): 5155-5166PubMed Google Scholar) examined the responses of hippocampal cells to systematic manipulations of a large set of spatial cues. Different place cells encoded individual proximal and distant stimuli, combinations of proximal or distant stimuli, or relations between proximal and distant cues. The place fields of some cells were fully controlled by as little as a single cue within a very complex environment, and most cells were controlled by different subsets of the controlled cues. Further examination of small ensembles of these cells recorded simultaneously confirmed that different cells were controlled by distinct subsets of the cues at the same time, indicating that the spatial representation was not cohesive (121Tanila H Shapiro M.L Eichenbaum H.E Discordance of spatial representation in ensembles of hippocampal place cells.Hippocampus. 1997; 7 (b): 613-623Crossref PubMed Scopus (112) Google Scholar). In several cases where two cells had overlapping place fields associated with one configuration of the cues, each cell responded differently when the same cues were rearranged. This finding shows that each cell was controlled by a different subset of the cues at the same time, and that their differential encodings are not due to shifts between two different spatial "reference frames" used by all cells at different times (34Gothard K.M Skaggs W.E McNaughton B.L Dynamics of mismatch correction in the hippocampal ensemble code for space interaction between path integration and environmental cues.J. Neurosci. 1996; 16 (b): 8027-8040PubMed Google Scholar). 113Skaggs W.E McNaughton B.L Spatial firing properties of hippocampal CA1 populations in an environment containing two visually identical regions.J. Neurosci. 1998; 18: 8455-8466Crossref PubMed Google Scholar confirmed this finding by recording from multiple hippocampal place cells simultaneously in rats foraging randomly in two identical enclosures, between which they could move freely. Each hippocampal ensemble contained cells that had similar place fields and others that had distinct spatial firing patterns between the two enclosures. In this situation, some cells encoded the physical cues, whereas the activity of others at the same time reflected the knowledge that the two environments were distinct (for variants on this observation, see 9Bostock E Muller R.U Kubie J.L Experience-dependent modifications of hippocampal place cell firing.Hippocampus. 1991; 1: 193-206Crossref PubMed Scopus (280) Google Scholar, 100Rotenberg A Muller R.U Variable place-cell coupling to a continuously viewed stimulus evidence that the hippocampus acts as a perceptual system.Philos. Trans. R. Soc. Lond. B Biol. Sci. 1997; 352: 1505-1513Crossref PubMed Scopus (58) Google Scholar, 44Jeffrey K.J Learning of landmark stability and instability by hippocampal place cells.Neuropharmacology. 1998; 37: 677-687Crossref PubMed Scopus (48) Google Scholar). Combining the findings from all of these studies, it appears that place fields involve a collection of independent representations, each one encoding the spatial relations between some subset of cues. Spatial representations are not bound as coordinates within a systematic framework for the global topology, indicating that hippocampal spatial codings are not organized as elements of a Cartesian "map." The absence of a systematic mapping does not preclude the existence of a map elsewhere in the brain, or of spatial information in hippocampal representations, and indeed several models have shown that an animal's location and direction of movement can be estimated by vector summation of place cell activities (e.g.14Burgess N O'Keefe J Neuronal computations underlying the firing of place cells and their role in navigation.Hippocampus. 1996; 7: 749-762Crossref Scopus (130) Google Scholar, 8Blum K.I Abbott L.F A