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Includes supplementary materials for the online appendix. The human posterior cingulate, retrosplenial, and medial parietal cortex are involved in memory and navigation. The functional anatomy underlying these cognitive functions was investigated by measuring the effective connectivity of these Posterior Cingulate Division (PCD) regions in the Human Connectome Project-MMP1 atlas in 171 HCP participants, and complemented with functional connectivity and diffusion tractography. First, the postero-ventral parts of the PCD (31pd, 31pv, 7m, d23ab, and v23ab) have effective connectivity with the temporal pole, inferior temporal visual cortex, cortex in the superior temporal sulcus implicated in auditory and semantic processing, with the reward-related vmPFC and pregenual anterior cingulate cortex, with the inferior parietal cortex, and with the hippocampal system. This connectivity implicates it in hippocampal episodic memory, providing routes for “what,” reward and semantic schema-related information to access the hippocampus. Second, the antero-dorsal parts of the PCD (especially 31a and 23d, PCV, and also RSC) have connectivity with early visual cortical areas including those that represent spatial scenes, with the superior parietal cortex, with the pregenual anterior cingulate cortex, and with the hippocampal system. This connectivity implicates it in the “where” component for hippocampal episodic memory and for spatial navigation. The dorsal–transitional–visual (DVT) and ProStriate regions where the retrosplenial scene area is located have connectivity from early visual cortical areas to the parahippocampal scene area, providing a ventromedial route for spatial scene information to reach the hippocampus. These connectivities provide important routes for “what,” reward, and “where” scene-related information for human hippocampal episodic memory and navigation. The midcingulate cortex provides a route from the anterior dorsal parts of the PCD and the supracallosal part of the anterior cingulate cortex to premotor regions. The research was supported by the following grants to Professor J. Feng: National Key R&D Program of China (No. 2019YFA0709502); 111 Project (No. B18015); Shanghai Municipal Science and Technology Major Project, ZJLab, and Shanghai Center for Brain Science and Brain-Inspired Technology (No. 2018SHZDZX01); and National Key R&D Program of China (No. 2018YFC1312904). G.D. is supported by a Spanish National Research Project funded by the Spanish Ministry of Science, Innovation and Universities (MCIU), State Research Agency (AEI) (ref. PID2019-105772GB-I00 MCIU AEI); HBP SGA3 Human Brain Project Specific Grant Agreement 3 (grant agreement no. 945539), funded by the EU H2020 FET Flagship programme; SGR Research Support Group Support (ref. 2017 SGR 1545), funded by the Catalan Agency for Management of University and Research Grants (AGAUR); Neurotwin Digital twins for model-driven non-invasive electrical brain stimulation (grant agreement ID: 101017716) funded by the EU H2020 FET Proactive Programme; euSNN European School of Network Neuroscience (grant agreement ID: 860563) funded by the EU H2020 MSCA-ITN Innovative Training Networks; CECH The Emerging Human Brain Cluster (Id. 001-P-001682) within the framework of the European Research Development Fund Operational Program of Catalonia 2014–2020; Brain-Connects: Brain Connectivity during Stroke Recovery and Rehabilitation (id. 201725.33) funded by the Fundacio La Marato TV3; Corticity, FLAG ERA JTC 2017, (ref. PCI2018-092891) funded by the Spanish Ministry of Science, Innovation and Universities (MCIU), State Research Agency (AEI). The funding agencies played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.

A new theory is proposed of mechanisms of navigation in primates including humans in which spatial view cells found in the primate hippocampus and parahippocampal gyrus are used to guide the individual from landmark to landmark. The navigation involves approach to each landmark in turn (taxis), using spatial view cells to identify the next landmark in the sequence, and does not require a topological map. Two other cell types found in primates, whole body motion cells, and head direction cells, can be utilized in the spatial view cell navigational mechanism, but are not essential. If the landmarks become obscured, then the spatial view representations can be updated by self-motion (idiothetic) path integration using spatial coordinate transform mechanisms in the primate dorsal visual system to transform from egocentric to allocentric spatial view coordinates. A continuous attractor network or time cells or working memory is used in this approach to navigation to encode and recall the spatial view sequences involved. I also propose how navigation can be performed using a further type of neuron found in primates, allocentric-bearing-to-a-landmark neurons, in which changes of direction are made when a landmark reaches a particular allocentric bearing. This is useful if a landmark cannot be approached. The theories are made explicit in models of navigation, which are then illustrated by computer simulations. These types of navigation are contrasted with triangulation, which requires a topological map. It is proposed that the first strategy utilizing spatial view cells is used frequently in humans, and is relatively simple because primates have spatial view neurons that respond allocentrically to locations in spatial scenes. An advantage of this approach to navigation is that hippocampal spatial view neurons are also useful for episodic memory, and for imagery.

Visual Place Recognition (VPR) is often characterized as being able to recognize the same place despite significant changes in appearance and viewpoint. VPR is a key component of Spatial Artificial Intelligence, enabling robotic platforms and intelligent augmentation platforms such as augmented reality devices to perceive and understand the physical world. In this paper, we observe that there are three "drivers" that impose requirements on spatially intelligent agents and thus VPR systems: 1) the particular agent including its sensors and computational resources, 2) the operating environment of this agent, and 3) the specific task that the artificial agent carries out. In this paper, we characterize and survey key works in the VPR area considering those drivers, including their place representation and place matching choices. We also provide a new definition of VPR based on the visual overlap -- akin to spatial view cells in the brain -- that enables us to find similarities and differences to other research areas in the robotics and computer vision fields. We identify numerous open challenges and suggest areas that require more in-depth attention in future works., Comment: Accepted to the International Joint Conference on Artificial Intelligence (IJCAI2021)

The hippocampus undergoes substantial postnatal maturation. This brain structure is central to episodic memory and allocentric spatial mapping, and infants lack these cognitive capacities until 18 months of age or older. The still-maturing hippocampus is especially sensitive to influences from environmental and genetic factors, helping us understand the patterns of developmental change associated with this region and its associated cognitive processes.

fMRI studies have identified distinct resting-state functional connectivity (RSFC) networks associated with the anterior and posterior hippocampus. However, the functional relevance of these two networks is still largely unknown. Hippocampal lesion studies and task-related fMRI point to a role for the anterior hippocampus in nonspatial episodic memory and the posterior hippocampus in spatial memory. We used Relevance Vector Regression (RVR), a machine-learning method that enables predictions of continuous outcome measures from multivariate patterns of brain imaging data, to test the hypothesis that patterns of whole-brain RSFC associated with the anterior hippocampus predict episodic memory performance, while patterns of whole-brain RSFC associated with the posterior hippocampus predict spatial memory performance. Magnetic resonance imaging and memory assessment took place at two separate occasions. The anterior and posterior RSFC largely corresponded with previous findings, and showed no effect of laterality. Supporting the hypothesis, RVR produced accurate predictions of episodic performance from anterior, but not posterior, RSFC, and accurate predictions of spatial performance from posterior, but not anterior, RSFC. In contrast, a univariate approach could not predict performance from resting-state connectivity. This supports a functional dissociation between the anterior and posterior hippocampus, and indicates a multivariate relationship between intrinsic functional networks and cognitive performance within specific domains, that is relatively stable over time.

The art of memory (ars memoriae) used since classical times includes using a well-known scene to associate each view or part of the scene with a different item in a speech. This memory technique is also known as the "method of loci." The new theory is proposed that this type of memory is implemented in the CA3 region of the hippocampus where there are spatial view cells in primates that allow a particular view to be associated with a particular object in an event or episodic memory. Given that the CA3 cells with their extensive recurrent collateral system connecting different CA3 cells, and associative synaptic modifiability, form an autoassociation or attractor network, the spatial view cells with their approximately Gaussian view fields become linked in a continuous attractor network. As the view space is traversed continuously (e.g., by self-motion or imagined self-motion across the scene), the views are therefore successively recalled in the correct order, with no view missing, and with low interference between the items to be recalled. Given that each spatial view has been associated with a different discrete item, the items are recalled in the correct order, with none missing. This is the first neuroscience theory of ars memoriae. The theory provides a foundation for understanding how a key feature of ars memoriae, the ability to use a spatial scene to encode a sequence of items to be remembered, is implemented. © 2017 Wiley Periodicals, Inc.

A theory and model of spatial coordinate transforms in the dorsal visual system through the parietal cortex that enable an interface via posterior cingulate and related retrosplenial cortex to allocentric spatial representations in the primate hippocampus is described. First, a new approach to coordinate transform learning in the brain is proposed, in which the traditional gain modulation is complemented by temporal trace rule competitive network learning. It is shown in a computational model that the new approach works much more precisely than gain modulation alone, by enabling neurons to represent the different combinations of signal and gain modulator more accurately. This understanding may have application to many brain areas where coordinate transforms are learned. Second, a set of coordinate transforms is proposed for the dorsal visual system/parietal areas that enables a representation to be formed in allocentric spatial view coordinates. The input stimulus is merely a stimulus at a given position in retinal space, and the gain modulation signals needed are eye position, head direction, and place, all of which are present in the primate brain. Neurons that encode the bearing to a landmark are involved in the coordinate transforms. Part of the importance here is that the coordinates of the allocentric view produced in this model are the same as those of spatial view cells that respond to allocentric view recorded in the primate hippocampus and parahippocampal cortex. The result is that information from the dorsal visual system can be used to update the spatial input to the hippocampus in the appropriate allocentric coordinate frame, including providing for idiothetic update to allow for self‐motion. It is further shown how hippocampal spatial view cells could be useful for the transform from hippocampal allocentric coordinates to egocentric coordinates useful for actions in space and for navigation.\ud \ud

Investigations into the neural basis of memory in human and non-human primates have focused on the hippocampus and associated medial temporal lobe (MTL) structures. However, how memory signals from the hippocampus affect motor actions is unknown. We propose that approaching this question through eye movement, especially by assessing the changes in looking behavior that occur with experience, is a promising method for exposing neural computations within the hippocampus. Here, we review how looking behavior is guided by memory in several ways, some of which have been shown to depend on the hippocampus, and how hippocampal neural signals are modulated by eye movements. Taken together, these findings highlight the need for future research on how MTL structures interact with the oculomotor system. Probing how the hippocampus reflects and impacts motor output during looking behavior renders a practical path to advance our understanding of the hippocampal memory system.

Hippocampal spatial view neurons in primates respond to the place where a monkey is looking, with some modulation by place. In contrast, hippocampal neurons in rodents respond mainly to the place where the animal is located. We relate this difference to the development of a fovea in primates, and the highly developed primate visual system which enables identification of what is at the fovea, and a system for moving the eyes to view different parts of the environment. We show that the spatial view representation in primates is allocentric, and provide new animations using recorded neuronal activity to illustrate this. We also show that this spatial representation becomes engaged in tasks in which the location 'out there' in a scene of objects and rewards must be remembered. We show that this representation of space being viewed provides a framework for the encoding of episodic memory and the recall of these memories in primates including humans, with hippocampal neurons responding for example in a one-trial object / place recall task. These functions of the primate hippocampus in scene-related memory, provide a way for the primate hippocampus to contribute to actions in space and navigation. We consider in a formal model the mechanisms by which these different spatial representations may be formed given the presence of the primate fovea, and how these mechanisms may contribute to the representations found during navigation in a virtual environment. [Abstract copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.]

This chapter describes a quantitative computational theory of hippocampal function, tests of predictions of the theory, and compares it to other theories. Based on the computational proposal that the dentate gyrus performs pattern separation by competitive learning and via the mossy fiber pathway forces new representations on the CA3 neurons during learning (encoding), it has been shown behaviorally that the dentate gyrus supports spatial pattern separation during learning and that the mossy fiber system to CA3 connections is involved in learning but not in recall. Based on the computational proposal that CA3–CA3 autoassociative networks are important for episodic or event memory of which space is a component (place in rodents and spatial view in primates), it has been shown behaviorally that the CA3 supports spatial rapid one-trial learning, and learning of arbitrary associations and pattern completion where space is a component. The concept that the CA1 recodes information from CA3 and sets up associatively learned backprojections to neocortex to allow subsequent retrieval of information to neocortex is consistent with findings on consolidation.

The hippocampus is a brain area crucial for episodic memory in humans. In contrast, studies in rodents have highlighted its role in spatial learning, supported by the discovery of place cells. Efforts to reconcile these views have found neurons in the rodent hippocampus that respond to non-spatial events but have not unequivocally dissociated the spatial and non-spatial influences on these cells. To disentangle these influences, we trained freely moving rats in trace eyeblink conditioning, a hippocampally dependent task in which the animal learns to blink in response to a tone. We show that dorsal CA1 pyramidal neurons are all place cells, and do not respond to the tone when the animal is moving. When the animal is inactive, the apparent tone-evoked responses reflect an arousal-mediated resumption of place-specific firing. These results suggest that one of the main output stages of the hippocampus transmits only spatial information, even in this non-spatial task. DOI: http://dx.doi.org/10.7554/eLife.14321.001

Memory for object-place configurations appears to be a common function of the hippocampus in the human and monkey brain. The nature of the spatial information which enters into these object-configural memories in the primate, and the location of the memories themselves, have remained obscure, however. In the rat, much evidence indicates that the hippocampus processes idiothetic spatial information, an estimate of the animal's current environmental location derived from path integration. I propose that in primates the hippocampus provides idiothetic information about the environmental location of body parts, and that the main function of this information in the primate brain is to become configured with object-identity information provided by temporal lobe cortex outside the hippocampus.

Single neuron recording studies have demonstrated the existence of spatial view neurons which encode information about the spatial location at which a primate is looking in the environment. These neurons are able to maintain their firing even in the absence of visual input. The standard neuronal network approach to model networks with memory that represent continuous spaces is that of continuous attractor neural networks. Stringer, Rolls and Trappenberg (2005) have recently shown how idiothetic (self-motion) inputs could update the activity packet of neuronal firing within a two-dimensional continuous attractor neural network of spatial view cells. However, this earlier study examined only the simplified situation in which the agent could rotate on the spot or move its eyes. In this paper we show how spatial view cells could be driven by head direction and place cells, themselves idiothetically updated. The head direction and place neurons are remapped by a competitive network with expansion recoding which self-organises so that different neurons represent different combinations of head direction and the place where the agent is located. The combination cells are then mapped by pattern association involving long-term synaptic potentiation but also long-term homosynaptic depression to spatial view cells, which during training are driven by the spatial view. After training, the spatial view cells are updated in the dark by the idiothetically driven head direction and place cells.

The primate anterior hippocampus (which corresponds to the rodent ventral hippocampus) receives inputs from brain regions involved in reward processing, such as the amygdala and orbitofrontal cortex. To investigate how this affective input may be incorporated into primate hippocampal function, we recorded neuronal activity while rhesus macaques performed a reward-place association task in which each spatial scene shown on a video monitor had one location that, if touched, yielded a preferred fruit juice reward and a second location that yielded a less-preferred juice reward. Each scene had different locations for the different rewards. Of 312 neurons analyzed in the hippocampus, 18% responded more to the location of the preferred reward in different scenes, and 5% responded to the location of the less-preferred reward. When the locations of the preferred rewards in the scenes were reversed, 60% of 44 hippocampal neurons tested reversed the location to which they responded, showing that the reward-place associations could be altered by new learning in a few trials. The majority (82%) of these 44 hippocampal neurons tested did not respond to reward associations in a visual discrimination, object-reward association task. Thus, the primate hippocampus contains a representation of the reward associations of places “out there” being viewed. By associating places with the rewards available, the concept that the primate hippocampus is involved in object-place event memory is now extended to remembering goals available at different spatial locations. This is an important type of association memory.

One literature treats the hippocampus as a purely cognitive structure involved in memory; another treats it as a regulator of emotion whose dysfunction leads to psychopathology. We review behavioral, anatomical, and gene expression studies that together support a functional segmentation into three hippocampal compartments: dorsal, intermediate, and ventral. The dorsal hippocampus, which corresponds to the posterior hippocampus in primates, performs primarily cognitive functions. The ventral (anterior in primates) relates to stress, emotion, and affect. Strikingly, gene expression in the dorsal hippocampus correlates with cortical regions involved in information processing, while genes expressed in the ventral hippocampus correlate with regions involved in emotion and stress (amygdala and hypothalamus).

In humans the hippocampus plays a role in both episodic memory and spatial navigation. Similar findings have been shown in other animals including monkeys and rats. The relationship between the processing of episodic and spatial related inputs within the hippocampus remains a puzzle. One approach to understanding how the hippocampus processes information is to examine how hippocampal cell activity corresponds to environmental experience. Hippocampal pyramidal cells can alter their spatial tuning (re-map) in response to changes in task demands. The degree to which this re-mapping is related to contextual/episodic information or to changes in spatial navigation/trajectories is unclear. The current study was designed to examine cell activity under two conditions that differed in contextual information without alterations in the goal-directed trajectories taken by the animals. Adult and aged rats were trained to do an alternation task on a fixed pathway [J. A. Oler et al. (2005)Neuroscience, 131, 1-12]. The animals ran this pathway during either 'safe' or 'unsafe' (a tone indicating a shock region) trials, with hesitation during 'unsafe' trials providing a clear behavioral measure of discrimination between these two conditions. Relatively few place cells displayed re-mapping between the two conditions. We propose that the principle source of re-mapping in the dorsal hippocampus is changes in the animal's trajectories rather than behavioral context. Possible reasons why so few cells responded to the change in context are discussed.

The parahippocampal cortex and hippocampus are brain structures known to be involved in memory. However, the unique contribution of the parahippocampal cortex remains unclear. The current study investigates memory for object identity and memory of the configuration of objects in patients with small thermo-coagulation lesions to the hippocampus or the parahippocampal cortex. Results showed that in contrast to control participants and patients with damage to the hippocampus leaving the parahippocampal cortex intact, patients with lesions that included the right parahippocampal cortex (RPH) were severely impaired on a task that required learning the spatial configuration of objects on a computer screen; these patients, however, were not impaired at learning the identity of objects. Conversely, we found that patients with lesions to the right hippocampus (RH) or left hippocampus (LH), sparing the parahippocampal cortex, performed just as well as the control participants. Furthermore, they were not impaired on the object identity task. In the functional Magnetic Resonance Imaging (fMRI) experiment, healthy young adults performed the same tasks. Consistent with the findings of the lesion study, the fMRI results showed significant activity in the RPH in the memory for the spatial configuration condition, but not memory for object identity. Furthermore, the pattern of fMRI activity measured in the baseline control conditions decreased specifically in the parahippocampal cortex as a result of the experimental task, providing evidence for task specific repetition suppression. In summary, while our previous studies demonstrated that the hippocampus is critical to the construction of a cognitive map, both the lesion and fMRI studies have shown an involvement of the RPH for learning spatial configurations of objects but not object identity, and that this takes place independent of the hippocampus.

The hippocampus is part of the cortex of the forebrain in mammals and is closely linked to a restricted number of related cortical areas that are here collectively referred to as the parahippocampal region. This collection of cortical regions, which in humans is located in the medial portion of the temporal lobe, is critically involved in learning and memory processes, in particular in episodic memory. This article aims to summarize the connectional organization of the hippocampal and parahippocampal domains, largely within the context of their relevance for episodic memory.

A fundamental question about the function of the primate including human hippocampus is whether object as well as allocentric spatial information is represented. Recordings were made from single hippocampal formation neurons while macaques performed an object-place memory task that required the monkeys to learn associations between objects and where they were shown in a room. Some neurons (10%) responded differently to different objects independently of location; other neurons (13%) responded to the spatial view independently of which object was present at the location; and some neurons (12%) responded to a combination of a particular object and the place where it was shown in the room. These results show that there are separate as well as combined representations of objects and their locations in space in the primate hippocampus. This is a property required in an episodic memory system, for which associations between objects and the places where they are seen are prototypical. The results thus provide an important advance by showing that a requirement for a human episodic memory system, separate and combined neuronal representations of objects and where they are seen “out there” in the environment, is present in the primate hippocampus.

The amygdala and hippocampus are key limbic structures of the temporal lobe, and are implicated in the pathology of mood disorders. Bcl-2, an intracellular protein, has recently been identified in the primate amygdala and hippocampus, and is now recognized as an intracellular target of mood stabilizing drugs. However, there are few data on the cellular phenotypes of bcl-2-expressing cells, or their distribution in specific subregions of the amygdala and hippocampus. We used a number of histochemical markers to define specific subregions of the primate amygdala and hippocampus, and examined phenotype-specific distributions of bcl-2 immunoreactive cells within each subregion. Immature-appearing bcl-2 labeled neurons, which co-contain class III beta-tubulin immunoreactivity, are found in distinct subregions in each structure. In the amygdala, bcl-2 positive neurons with an immature morphology are densely distributed in the paralaminar nucleus and intercalated cell islands, the parvicellular basal nucleus, and the ventral periamygdaloid cortex and amygdalohippocampal area. In the hippocampus, immature-appearing bcl-2-labeled cells are confined to the polymorph layer (subgranular zone), and base of the granule cell layer in the dentate gyrus. Well-differentiated neurons also express bcl-2. In the amygdala, labeled cells with mature phenotypes are concentrated in the parvicellular basal nucleus, the accessory basal nucleus, and the periamygdaloid cortex. The medial nucleus and central extended amygdala also contain many well-differentiated bcl-2 positive cells. In the hippocampus, the dentate gyrus and Ammon's horn contain many bcl-2 immunoreactive nonpyramidal cells. These are preferentially distributed in the rostral hippocampus. CA3 and CA2 contain relatively higher concentrations of bcl-2-labeled cells than CA1 and the subiculum. Bcl-2 is thus important in intrinsic circuitry of the hippocampus, and in amygdaloid subregions modulated by the hippocampus. In addition, the extended amygdala, a key amygdaloid output, is richly endowed with bcl-2 positive cells. This distribution suggests a role for bcl-2 in circuits mediating emotional learning and memory which may be targets of mood stabilizing drugs.

Place cells of the rodent hippocampus constitute one of the most striking examples of a correlation between neuronal activity and complex behaviour in mammals1,2. These cells increase their firing rates when the animal traverses specific regions of its surroundings, providing a context-dependent map of the environment3,4,5. Neuroimaging studies implicate the hippocampus and the parahippocampal region in human navigation6,7,8. However, these regions also respond selectively to visual stimuli9,10,11,12,13. It thus remains unclear whether rodent place coding has a homologue in humans or whether human navigation is driven by a different, visually based neural mechanism. We directly recorded from 317 neurons in the human medial temporal and frontal lobes while subjects explored and navigated a virtual town. Here we present evidence for a neural code of human spatial navigation based on cells that respond at specific spatial locations and cells that respond to views of landmarks. The former are present primarily in the hippocampus, and the latter in the parahippocampal region. Cells throughout the frontal and temporal lobes responded to the subjects' navigational goals and to conjunctions of place, goal and view.

Single-neuron recording studies have demonstrated the existence of neurons in the hippocampus which appear to encode information about the place where a rat is located, and about the place at which a macaque is looking. We describe 'continuous attractor' neural network models of place cells with Gaussian spatial fields in which the recurrent collateral synaptic connections between the neurons reflect the distance between two places. The networks maintain a localized packet of neuronal activity that represents the place where the animal is located. We show for two related models how the representation of the two-dimensional space in the continuous attractor network of place cells could self-organize by modifying the synaptic connections between the neurons, and also how the place being represented can be updated by idiothetic (self-motion) signals in a neural implementation of path integration.

The human hippocampus is a highly complex structure located on the medial surface of the cerebral hemispheres as a part of the intralimbic gyrus. For clinical purposes, in addition to routine transverse MRI slices, acquisitions parallel and perpendicular to the long axis of the hippocampus need to be performed to fully appreciate its curved anatomy. Clinicians should be acquainted with the normal appearance of the hippocampus regarding size, shape, symmetry, and signal as well as with the width and form of the cerebrospinal fluid spaces surrounding the hippocampus to be able to recognize abnormalities. The human hippocampus can be affected in a variety of very different acute or chronic neurological diseases, such as stroke and certain forms of encephalitis or epilepsy and dementia. Many of these pathologies are associated with distinct lesion patterns on conventional MRI. In hippocampal sclerosis, the typical imaging features - T2 hyperintensity, atrophy on T1-weighted images, and disturbed internal structures of the hippocampus - can be reliably diagnosed by visual analysis. Several visual rating scales exist for the evaluation of medial temporal lobe atrophy for the assessment of patients with cognitive disturbances; however, quantitative MRI-based volumetric analysis is increasingly being applied in research as well as clinical studies. In acute neurological disorders, diffusion-weighted imaging has the ability to demonstrate even minute and transient hyperintense hippocampal lesions. On the basis of distinct lesions patterns, diffusion-weighted MRI can provide additional diagnostic information that may facilitate and support a final diagnosis, especially in those cases in which clinical symptoms are inconclusive.

The hippocampus is a temporal brain structure belonging to the limbic lobe and is fundamentally involved in memory processing, learning, and emotions. It consists of two allocortex laminae: the gyrus dentatus and the cornu ammonis, one rolled up inside the other, creating a bulge in the temporal horn of the lateral ventricle. Arterial vascularization of the hippocampus is dependent on the collateral branches of the posterior cerebral artery and the anterior choroidal artery, forming the network of superficial hippocampal arteries that in turn lead to deep intrahippocampal arteries. Venous vascularization is provided by the intrahippocampal veins, which drain into the superficial hippocampal veins. Knowledge of anatomical organization and vascularization of the hippocampus is essential to understanding its dysfunctions and its appearance on MRI.

Hippocampal function was analysed by making recordings from hippocampal neurons in monkeys actively walking in the laboratory. 'Spatial view' cells, which respond when the monkey looks at a part of the environment, were analysed. It is shown that these cells code for the allocentric position in space being viewed and not for eye position, head direction or the place where the monkey is located. This representation of space 'out there' would be an appropriate part of a primate memory system involved in memories of where in an environment an object was seen, and more generally in the memory of particular events or episodes, for which a spatial component normally provides part of the context.

The information represented in the primate hippocampus is being analysed by making recordings in monkeys actively walking in the laboratory. In a sample of 352 cells recorded in this situation, no "place" cells have so far been found. Instead, we have found a considerable population of "spatial view" cells tuned to respond when the monkey looks at small parts of the environment. We have been able to demonstrate (1) that these hippocampal neurons respond to a view of space "out there," not to the place where the monkey is; (2) that the responses depend on where the monkey is looking, by measuring eye position; (3) that the responses in some cases (e.g., CA1 but not CA3) still occur if the view details are obscured with curtains; (4) that the cells (in, e.g., CA1) retain part of their "space" tuning even in complete darkness, for several minutes; and (5) that the spatial representation is allocentric. The spatial representation is, thus, different from that in the rat hippocampus, in which place cells respond based on where the rat is located. The representation is also different from that described in the parietal cortex, where neurons respond in egocentric coordinates. This representation of space "out there" provided by primate spatial view cells would be an appropriate part of a memory system involved in memories of particular events or episodes, for example, of where in an environment an object was seen. Spatial view cells (in conjunction with whole body motion cells in the primate hippocampus, and head direction cells in the primate presubiculum) would also be useful as part of a spatial navigation system, for which they would provide a memory component.

The function of the primate hippocampus and related structures was analysed by making recordings from the hippocampus, subiculum, presubiculum, and parahippocampal gyrus in monkeys actively walking in the laboratory. Head direction cells were found in the presubiculum. The firing rate of these cells was a function of the head direction of the monkey, with a response that was typically 10–100 times larger to the best as compared to the opposite direction. The mean half-amplitude width of the tuning of the cells was 76°. The response of head direction cells in the presubiculum was not influenced by the place where the monkey was, there being the same tuning to head direction at different places in a room, and even outside the room. The response of these cells was also independent of the “spatial view” observed by the monkey, and also the position of the eyes in the head. The average information about head direction was 0.64 bits, about place was 0.10 bits, about spatial view was 0.27 bits, and about eye position was 0.04 bits. The cells maintained their tuning for periods of at least several minutes when the view details were obscured or the room was darkened. This representation of head direction could be useful together with the hippocampal spatial view cells and whole body motion cells found in primates in such spatial and memory functions as path integration. Hippocampus 1999; 9:206–219. © 1999 Wiley-Liss, Inc.

Over 50 years ago, [Scoville and Milner (1957)][1] reported the case of H. M., an epileptic patient who underwent bilateral removal of his medial temporal lobe, a region of the brain that encompasses the hippocampus. After the surgery, H. M. was unable to form new memories, highlighting the

Experimental evidence suggests that the hippocampus represents locations within an allocentric representation of space. The environmental inputs that underlie the rat’s representa­tion of its own location within an environment (in the firing of place cells) are the distances to walls, and different walls are identified by their allocentric direction from the rat. We propose that the locations of goals in an environment is stored downstream of the place cells, in the subiculum. In addition to firing rate coding, place cells may use phase coding relative to the theta rhythm of the EEG. In some circumstances path integration may be used, in addition to environmental information, as an input to the hippocampal system. A detailed computational model of the hippocampus successfully guides the navigation of a mobile robot. The model’s behaviour is compared to electrophysiological and behavioural data in rats, and implications for the role of the hippocampus in primates are explored.

Robertson, Robert G., Edmund T. Rolls, and Pierre Georges-François. Spatial view cells in the primate hippocampus: effects of removal of view details. J. Neurophysiol. 79: 1145–1156, 1998. Hippocampal function was analyzed by making recordings from hippocampal formation neurons in macaques actively walking in the laboratory. “Spatial view” cells, which respond when the monkey looks at a part of the environment were analyzed. It is shown that many of these cells retain their spatial characteristics when the view details are obscured totally by curtains and by darkness. It is shown that many of these cells respond more when the monkey is gazing toward one location in the room than toward other locations, even though none of the view details can be seen. Such cells were found in the CA1 region, the parahippocampal gyrus, and the presubiculum. Other cells stopped responding when the monkey looked toward the normally effective location in the environment if the view details were obscured. These cells were in the CA3 region of the hippocampus. The results indicate that for CA3 cells, the visual input is necessary for the normal spatial response of the neurons, and for other cells in the primate hippocampal formation, the response still depends on the monkey gazing toward that location in space when the view details are obscured. These latter cells therefore could reflect the operation of a memory system, in which the neuronal activity can be triggered by factors that probably include not only eye position command/feedback signals, but also probably vestibular and/or proprioceptive inputs. This representation of space “out there” would be an appropriate part of a primate memory system involved in memories of where in an environment an object was seen and more generally in the memory of particular events or episodes for which a spatial component normally provides part of the context.

A minimal synaptic architecture is proposed for how the brain might perform path integration by computing the next internal representation of self-location from the current representation and from the perceived velocity of motion. In the model, a place-cell assembly called a “chart” contains a two-dimensional attractor set called an “attractor map” that can be used to represent coordinates in any arbitrary environment, once associative binding has occurred between chart locations and sensory inputs. In hippocampus, there are different spatial relations among place fields in different environments and behavioral contexts. Thus, the same units may participate in many charts, and it is shown that the number of uncorrelated charts that can be encoded in the same recurrent network is potentially quite large. According to this theory, the firing of a given place cell is primarily a cooperative effect of the activity of its neighbors on the currently active chart. Therefore, it is not particularly useful to think of place cells as encoding any particular external object or event. Because of its recurrent connections, hippocampal field CA3 is proposed as a possible location for this “multichart” architecture; however, other implementations in anatomy would not invalidate the main concepts. The model is implemented numerically both as a network of integrate-and-fire units and as a “macroscopic” (with respect to the space of states) description of the system, based on a continuous approximation defined by a system of stochastic differential equations. It provides an explanation for a number of hitherto perplexing observations on hippocampal place fields, including doubling, vanishing, reshaping in distorted environments, acquiring directionality in a two-goal shuttling task, rapid formation in a novel environment, and slow rotation after disorientation. The model makes several new predictions about the expected properties of hippocampal place cells and other cells of the proposed network.

Hippocampal function was analysed by making recordings in rhesus monkeys actively walking in the laboratory. In a sample of 352 cells recorded in the hippocampus and parahippocampal cortex, a population of ‘spatial view’ cells was found to respond when the monkey looked at a part of the environment. The responses of these hippocampal neurons (i) occur to a view of space ‘out there’, not to the place where the monkey is, (ii) depend on where the monkey is looking, as shown by measuring eye position, (iii) do not encode head direction, and (iv) provide a spatial representation that is allocentric, i.e. in world coordinates. This representation of space ‘out there’ would be an appropriate part of a primate memory system involved in memories of where in an environment an object was seen, and more generally in the memory of particular events or episodes, for which a spatial component normally provides part of the context.

Since the early 1960s, researchers have speculated that the vestibular system, the sensory system concerned with the perception of balance and self-motion, contributes to spatial information processing and the development of spatial memory in the hippocampus. Anatomical studies have suggested that various parts of the thalamus are likely to transmit vestibular information to the hippocampus, perhaps via the parietal cortex; however, more direct pathways are possible. Over the last 2-3 years there have been a number of direct electrophysiological demonstrations that vestibular stimulation affects head direction cells in the anterior thalamic nuclei and place cells in the hippocampus. These studies demonstrate the importance of vestibular-hippocampal interactions for hippocampal function but also raise the possibility that the hippocampus may be important for compensation of vestibular function following peripheral or central vestibular lesions.

To analyze the information provided about individual visual stimuli in the responses of single neurons in the primate temporal lobe visual cortex, neuronal responses to a set of 65 visual stimuli were recorded in macaques performing a visual fixation task and analyzed using information theoretical measures. The population of neurons analyzed responded primarily to faces. The stimuli included 23 faces and 42 nonface images of real-world scenes, so that the function of this brain region could be analyzed when it was processing relatively natural scenes. It was found that for the majority of the neurons significant amounts of information were reflected about which of several of the 23 faces had been seen. Thus the representation was not local, for in a local representation almost all the information available can be obtained when the single stimulus to which the neuron responds best is shown. It is shown that the information available about any one stimulus depended on how different (for example, how many standard deviations) the response to that stimulus was from the average response to all stimuli. This was the case for responses below the average response as well as above. It is shown that the fraction of information carried by the low firing rates of a cell was large - much larger than that carried by the high firing rates. Part of the reason for this is that the probability distribution of different firing rates is biased toward low values (though with fewer very low values than would be predicted by an exponential distribution). Another factor is that the variability of the response is large at intermediate and high firing rates. Another finding is that at short sampling intervals (such as 20 ms) the neurons code information efficiently, by effectively acting as binary variables and behaving less noisily than would be expected of a Poisson process.