Role of active movement in place-specific firing of hippocampal neurons

The extent of external and internal factors contributing to location-specific firing of hippocampal place cells is currently unclear. We investigated the role of active movement in location-specific firing by comparing spatial firing patterns of hippocampal neurons, while rats either ran freely or rode a motorized cart on the same circular track. Most neurons changed their spatial firing patterns across the two navigation conditions ("remapping"), and they were stably maintained across repeated active or passive navigation sessions. These results show that active movement is a critical factor in determining place-specific firing of hippocampal neurons. This could explain why passive displacement is not an effective way of acquiring spatial knowledge for subsequent active navigation in an unfamiliar environment.     

Head direction cells in the primate pre‐subiculum

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.     

Evolutionary shifts dramatically reorganized the human hippocampal complex

The hippocampal complex (HC) is central to long-term memory storage and retrieval as well as spatial navigation across many species. Notably, humans appear to have greatly enhanced and possibly unique HC-mediated capacities such as constructive episodic simulation. Key studies have shown that the human HC is disproportionately large amongst hominoids, but much remains unknown at the levels of substructural evolutionary reorganization and ecological selection. Here, we calculated relative sizes of 12 HC subregions in a diverse sample of 44 primate species. We then used a Bayesian phylogenetic method, selective regime analysis, to identify 27 separate evolutionary shifts in HC organization across 65 million years of primate evolution. Additionally, a series of multivariate phylogenetic regressions using HC-related ecological variables as predictors (Diet Breadth, Population Density, Group Size, Home Range Size, and Residual Home Range) revealed that relative fascia dentata and CA1 size were both significantly predicted by species' home range size (after correcting for body size). However, perhaps the most notable finding of this study was that the shifts in HC size and subregional organization in the human lineage were the largest seen in all of primate evolution, rendering modern humans with a HC that is a clear outlier amongst all nonhuman primates investigated here. Given the extensive literature confirming the relationship between HC organization and function, these selective shifts are likely to have played a significant role in the emergence of human-specific capacities, such as constructive episodic simulation.     

Reward value invariant place responses and reward site associated activity in hippocampal neurons of behaving rats

To investigate the involvement of the hippocampal-accumbens system in goal-oriented displacement behaviors, hippocampal neuronal activity was recorded in rats learning and recalling new distributions of different volumes of liquid reward among the arms of a plus maze. Each arm had a reward box containing a water trough and identical visual cues that could be illuminated independently. As the water-restricted rat successively visited the respective boxes, it received 7, 5, and 3 drops of water, and then 1 drop, provided at 1-s intervals. (Reward distributions were reassigned daily and mid-session.) In the training phase, reward boxes were lit individually. In the recall phase, the lamps on all arms were lit and then turned off as the rat visited the boxes in order of descending value. Neuronal firing rates were analyzed for changes related to reward value or to shifts between learning and recall phases. The principal finding is that place responses remained unchanged after these manipulations and that these neurons showed no evidence of explicit coding of reward value. In addition, two other types of responses appeared while the rat was stationary at the reward boxes awaiting multiple rewards. These were observed primarily in neurons within the dentate gyrus, but also in CA1. Position-selective reward site responses were regular at 20-60 impulses per second, while position-independent discharges bursted irregularly at about 5 impulses per second. Such responses could explain controversial reports of reward dependence in hippocampal neurons. The higher incidence of the latter responses in the temporal ("ventral") hippocampus is consistent with the distinctive anatomical and functional properties of this subregion.     

Spatial coordinate transforms linking the allocentric hippocampal and egocentric parietal primate brain systems for memory,action in space,and navigation

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.     

Perseveration on place reversals in spatial swimming pool tasks: Further evidence for place learning in hippocampal rats

Animals with damage to the fimbria–fornix (FF) or cells of the hippocampus (HIP) can learn a place problem but cannot learn matching-to-place problems, which feature a series of place “reversals.” The two experiments described in the present report were designed to examine the causes of impairment on reversal learning. In experiment 1, control, HIP, and FF groups were trained to asymptote on a place problem, and then the location of the platform was moved. Control rats learned the reversal response more quickly than the initial response; the HIP rats learned both problems at the same rate. Swim analysis showed that the impairment in the lesion group on the reversal response was aggravated by perseverative returns to the first learned place. In experiment 2, control and FF groups were trained on a task in which the platform was visible on three daily trials and hidden on one daily trial. After 10 days, the platforms were moved. In the reversal response, the FF group showed enhanced performance on the cue trials and severely impaired performance on the place trials relative to initial learning and control performance. Swim analysis showed that FF rats perseverated on the initial place response in place trials. These experiments provide further evidence for place learning in hippocampal rats and show that perseverative responses contribute to impairments in new learning. The results are discussed in relation to the idea that the hippocampus mediates spatial mapping and/or uses self-movement cues to solve spatial problems. Hippocampus 7:361–370, 1997. © 1997 Wiley-Liss, Inc.     

Spatial selectivity of unit activity in the hippocampal granular layer

Single neuron activity was recorded in the granular layer of the fascia dentata in freely moving rats, while the animals performed a spatial “working” memory task on an eight-arm maze. Using recording methods that facilitate detection of units with low discharge rates, it was found that the majority (88%) of cells in this layer have mean rates below 0.5 Hz, with a minimum of 0.01 Hz or less. The remaining recorded cells exhibited characteristics typical of the theta interneurons found throughout the hippocampus. Based on several criteria including relative proportion and the relation of their evoked discharges to the population spike elicited by perforant path stimulation, it was concluded that the low-rate cells correspond to granule cells. Granule cells exhibited clear spatially and directionally selective discharge that was at least as selective as that of a sample of CA3 pyramidal cells recorded under the same conditions. Granule cells had significantly smaller place fields than pyramidal cells, and tended to have more discontiguous subfields. There was no spatial correlation among simultaneously recorded adjacent granule cells. Granule cells also exhibited burst discharges reminiscent of complex spikes from pyramidal cells while the animals sat quietly; however, the spike duration of granule cells was significantly shorter than CA3 pyramidal cell spike durations. Under conditions of environmental stability, granule cell place fields were stable for at least several days. Following occasional maze rotations relative to the (somewhat impoverished) visual stimuli of the recording room, granule cell place fields were maintained relative to the distal spatial cues; however, frequent rotations of the maze sometimes resulted in a shift in the reference frame to the maze itself. These observations indicate that granule cells of the fascia dentata provide their CA3 targets with a high degree of spatial information, in the form of a sparsely coded, distributed representation.     

Spatial View Cells in the Primate Hippocampus

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.     

Tactile modulation of hippocampal place fields

Neural correlates of spatial representation can be found in the activity of the hippocampal place cells. These neurons are characterized by firing whenever the animal is located in a particular area of the space, the place field. Place fields are modulated by sensory cues, such as visual, auditory, or olfactory cues, being the influence of visual inputs the most thoroughly studied. Tactile information gathered by the whiskers has a prominent representation in the rat cerebral cortex. However, the influence of whisker‐detected tactile cues on place fields remains an open question. Here we studied place fields in an enriched tactile environment where the remaining sensory cues were occluded. First, place cells were recorded before and after blockade of tactile transmission by means of lidocaine applied on the whisker pad. Following tactile deprivation, the majority of place cells decreased their firing rate and their place fields expanded. We next rotated the tactile cues and 90% of place fields rotated with them. Our results demonstrate that tactile information is integrated into place cells at least in a tactile‐enriched arena and when other sensory cues are not available. © 2013 Wiley Periodicals, Inc.     

Discordance of spatial representation in ensembles of hippocampal place cells

The extent to which small ensembles of neighboring hippocampal neurons alter their spatial firing patterns concurrently in response to stimulus manipulations was examined in young adult rats as well as in aged rats with and without memory impairment. Recordings from CA1 and CA3 cells were taken as rats performed a spatial radial-maze task that employed prominent distal visual stimuli attached to dark curtains surrounding the maze and local cues on each maze arm provided by inserts with distinctive visual, tactile, and olfactory stimuli. To test the influence of the different stimulus subsets, the distal and local cues were rotated 90° in opposite directions (a Double Rotation). In response to this manipulation, place fields could maintain a fixed position to room coordinates, rotate with either the local or the distal cues, disappear, or new fields could appear. On average 79% of the cells within an ensemble responded in the same way, but only 37% of all ensembles were fully concordant. Typically discordant ensembles had place fields that rotated with one set of cues, whereas the other fields disappeared or new fields appeared. Ensembles in which the place fields rotated in two opposite directions were less frequent in young rats than would be expected by the occurrence of the individual responses, indicating selective competition between directly conflicting representations and ultimate suppression of one. These findings indicate that hippocampal neurons independently encode distinct subsets of the cues in a complex environment, although processing within the hippocampal network may actively reduce the simultaneous representation of conflicting orientation information. This kind of population activity might reflect the higher-order organization of new memories within an established knowledge framework or schema. Concordance was higher in aged memory-impaired rats than in young rats, and the suppression of conflicting representations was absent in these rats. These findings suggest that age-related memory impairment is at least in part associated with a decrease in the scope of information coded and in the coordination of encoded representations. Hippocampus 1997;7:613–623. © 1997 Wiley-Liss, Inc.     

Place fields of rat hippocampal pyramidal cells and spatial learning in the watermaze

To provide a background for studying place-related activity in hippocampal neurons during spatial learning, we compared the activity of hippocampal place cells in an annular watermaze and an analogous land-based task. Complex-spike cells had robust place correlates in both conditions, and a significant proportion of the cells had place fields at the same locations. However, the in-field firing rates were slightly higher in the wet condition. Elevated firing was observed also in an open water task. There was no enhancement when the platform location was varied randomly or when there was no platform at all. Second, the place fields were under stronger directional modulation during swimming. In the annular task, directional sensitivity appeared regardless of whether the animals were trained to find a platform or not. There were directionally modulated units also in the open watermaze, but the number was smaller than in the corridor. Altogether, these observations suggest that place fields in the watermaze are largely controlled by the same factors as on dry land, in spite of the differences in kinaesthetic and vestibular input. Differences in firing rate and directional control may depend on the geometric and cognitive structure of the task rather than the medium on which the rats are moving.     

Slow stabilization of concurrently acquired hippocampal context representations

Hippocampal neurons exhibit spatially localized firing patterns that, at the population level, represent a particular environment or context. Many studies have examined how hippocampal neurons switch from an existing representation to a new one when the environment is changed, a process referred to as remapping. New representations were commonly thought to emerge rapidly, within a few minutes and then remain remarkably stable thereafter. However, a number of recent studies suggest that hippocampal representations may be more fluid than previously thought and most of the previous studies only required that subjects switch from a familiar environment to a novel one. In the present study, we examined the concurrent development of two distinct hippocampal representations by exposing rats to two distinct environmental contexts in an ABAB pattern and we recorded neuronal activity for eight daily training sessions. Hippocampal neurons exhibited normal place fields with typical firing properties during the initial exposure to each context on the first day. However, when the rats were returned to the original context after having spent 15 min in the second context, many of the neurons fired in new locations (i.e., they remapped) as if the rat had encountered a new environment. By the third day, the representations had stabilized and were highly consistent across visits to the same context. These results suggest that when subjects concurrently encode multiple contexts, hippocampal representations may require repeated experiences to fully stabilize. © 2016 Wiley Periodicals, Inc.     

Exploring the role of context-dependent hippocampal activity in spatial alternation behavior

In a continuous T-maze spatial alternation task, CA1 place cells fire differentially on the stem of the maze as rats are performing left- and right-turn trials (Wood et al. (2000) Neuron 27:623-633). This context-dependent hippocampal activity provides a potential mechanism by which animals could solve the alternation task, as it provides a cue that could prime the appropriate goal choice. The aim of this study was to examine the relationship between context-dependent hippocampal activity and spatial alternation behavior. We report that rats with complete lesions of the hippocampus learn and perform the spatial alternation task as well as controls if there is no delay between trials, suggesting that the observed context-dependent hippocampal activity does not mediate alternation behavior in this task. However lesioned rats are significantly impaired when delays of 2 or 10 s are interposed. Recording experiments reveal that context-dependent hippocampal activity occurs in both the delay and no-delay versions of the task, but that in the delay version it occurs during the delay period, and not on the stem of the maze. These data are consistent with a role for context-dependent hippocampal activity in delayed spatial alternation, but suggest that, according to specific task demands and memory load, the activity may be generated by different mechanisms and/or in different brain structures.     

Evidence for extrahippocampal involvement in place learning and hippocampal involvement in path integration

Although there is a good deal of evidence that animals require the hippocampus for learning place responses, animals with damage to the afferent and efferent fibers coursing through the fimbria-fornix have been shown to acquire a place response. This finding suggests either that the cells of the hippocampus proper (CA1–4 and dentate gyrus), via their connections to the temporal lobe, can mediate place learning or that some extrahippocampal structure is sufficient. We examined this question using rats with ibotenic acid lesions of the cells of the hippocampus. Rats were pretrained to swim to a visible platform and then given probe trials on which the visible platform was removed. Video and kinematic analyses showed that the hippocampal rats expected to find the platform at its previous location because they swam directly to that location and paused and turned at that location after the platform was removed. Additional tests confirmed that they had learned a place response. There were, however, abnormalities in their swimming patterns, and despite having acquired one place response, they did not then acquire new place responses when only the hidden platform training procedure was used. These results demonstrate that place learning can be acquired by rats in which the hippocampus proper is removed. Contrasts between conditions in which hippocampal rats acquire a place response and conditions in which they fail suggests that the hippocampus may serve as an on line system for monitoring movement and integrating movement paths. © 1996 Wiley-Liss, Inc.     

Transient optogenetic inactivation of the medial entorhinal cortex biases the active population of hippocampal neurons

The mechanisms that enable the hippocampal network to express the appropriate spatial representation for a particular circumstance are not well understood. Previous studies suggest that the medial entorhinal cortex (MEC) may have a role in reproducibly selecting the hippocampal representation of an environment. To examine how ongoing MEC activity is continually integrated by the hippocampus, we performed transient unilateral optogenetic inactivations of the MEC while simultaneously recording place cell activity in CA1. Inactivation of the MEC caused a partial remapping in the CA1 population without diminishing the degree of spatial tuning across the active cell assembly. These changes remained stable irrespective of intermittent disruption of MEC input, indicating that while MEC input is integrated over long time scales to bias the active population, there are mechanisms for stabilizing the population of active neurons independent of the MEC. We find that MEC inputs to the hippocampus shape its ongoing activity by biasing the participation of the neurons in the active network, thereby influencing how the hippocampus selectively represents information. © 2015 Wiley Periodicals, Inc.     

Context-independent directional cue learning by hippocampal place cells

In a symmetrical environment possessing no other polarizing visual cues, the spatially localized firing of hippocampal place cells can be primarily orientated by a reliable distal visual stimulus, such as a white cue card. However, if such a directional cue is made unreliable by being frequently moved in full view of the rat, the rat's internal sense of direction comes, over the course of a few days, to control the orientation of place fields instead. We investigated whether this simple form of 'cue-instability' learning would transfer to a new context, in which the firing patterns of the place cells become reorganized and in which a new spatial representation is thus active. We found that after cue-instability learning, the 'remapped' place field representation in the new environment was also orientated by the internal sense of direction of the rat rather than by the cue card, showing that the cue learning generalized from one context (and hence spatial representation) to another. This contrasts with another kind of place cell learning, in which the cells can acquire the ability to discriminate two spatial locations in one context but do not transfer this discrimination to a new context. We discuss the different effects of context changes on learned place cell activity in terms of the possible architecture of the inputs to place cells.     

Similarities vs. differences in place learning and circadian activity in rats after fimbria-fornix section or ibotenate removal of hippocampal cells

Damage to either the fimbria-fornix or to the hippocampus can produce a deficit in spatial behavior and change in locomotor activity but the extent to which the two kinds of damage are comparable is not known. Here we contrasted the effects of cathodal sections of the fimbria-fornix with ibotenic acid lesions of the cells of the hippocampus (Ammon's horn and the dentate gyrus) on place learning in a swimming pool and on circadian activity. Rats in both ablation groups were impaired relative to control rats in learning a single place response but they did acquire the response as measured by swim latencies, errors, and by enhanced searching on probe trials. They were also more active than the control group on the test of activity. Nevertheless, the fimbria-fornix group was initially more impaired on learning and was more active than the hippocampal group. Analysis of the strategies used in learning indicated that the lesion groups were very similar to each other but different from the control group especially in that at asymptotic performance, rats in both lesion groups made rather tight loops as they swam toward the platform. This strategy likely contributed to the greater proportion of time they spent swimming in the correct quadrant on the subsequent probe trial. These findings confirm that rats with fimbria-fornix or hippocampal damage display impairments in place learning and are hyperactive but also show that there are lesion differences. The results are discussed with respect to the relative effectiveness of the lesions and the possibility that fibers in the fimbria-fornix may mediate some functions that are not attributable to the hippocampus. © 1995 Wiley-Liss, Inc.     

Non-spatial expertise and hippocampal gray matter volume in humans

Previous work suggests that spatial expertise in licensed London taxi drivers is associated with differences in hippocampal gray matter volume relative to IQ-matched control subjects. Here we examined whether non-spatial expertise is associated with similar hippocampal gray matter effects. We compared medical doctors who, like taxi drivers, acquire a vast amount of knowledge over many years, with IQ-matched control subjects who had no tertiary education. Whole brain analysis of structural magnetic resonance imaging (MRI) scans using voxel-based morphometry (VBM) failed to identify any differences in gray matter volume between the groups, including in the hippocampus. Moreover, amount of medical experience that ranged from 0.5 to 22.5 yr did not correlate with gray matter volume in the hippocampus or elsewhere in the brain. We conclude that intensively acquiring a large amount of knowledge over many years is not invariably associated with hippocampal gray matter volume differences. Instead it would seem that hippocampal gray matter volume effects are more likely to be observed when the knowledge acquired concerns a complex and detailed large-scale spatial layout.     

Local inhibition of hippocampal nitric oxide synthase does not impair place learning in the Morris water escape task in rats

Recent studies have provided evidence that nitric oxide (NO) has a role in certain forms of memory formation. Spatial learning is one of the cognitive abilities that has been found to be impaired after systemic administration of an NO-synthase inhibitor. As the hippocampus has a pivotal role in spatial orientation, the present study examined the role of hippocampal NO in spatial learning and reversal learning in a Morris task in adult rats. It was found that N^ω-nitro-l -arginine infusions into the dorsal hippocampus affected the manner in which the rats were searching the submerged platform during training, but did not affect the efficiency to find the spatial location of the escape platform. Hippocampal NO-synthase inhibition did not affect the learning of a new platform position in the same water tank (i.e. reversal learning). Moreover, no treatment effects were observed in the probe trials (i.e. after acquisition and after reversal learning), indicating that the rats treated with N^ω-nitro-l -arginine had learned the spatial location of the platform. These findings were obtained under conditions where the NO synthesis in the dorsal hippocampus was completely inhibited. On the basis of the present data it was concluded that hippocampal NO is not critically involved in place learning in rats.