Quantification of a single exploratory trip reveals hippocampal formation mediated dead reckoning.

A rat's proclivity to explore a novel environment presents a behaviorally rich paradigm to investigate the role of the hippocampus in spatial navigation. Here we describe a novel technique of behavioral analysis that is derived from a single exploratory trip. An exploratory trip was defined as a rat's departure from the home base that ended when the rat returned to the home base. The behavior observed on a single exploratory trip by a control animal is highly organized into outward and homeward segments. An outward segment is characterized by a slow circuitous progression from the home base marked by several stops. A homeward segment is characterized by a rapid direct return to the home base. The velocity attribute of the exploratory trip was quantified by estimating the point of inflection associated with the trip's cumulative moment-to-moment velocity distribution. The heading direction and variance of the homeward trip segment was analyzed with circular statistics. A comparison of the exploratory behavior of control animals and animals with damage to the fimbria-fornix indicated that the velocity and heading direction of the homeward portion of the trip depends upon the hippocampal formation. While control and fimbria-fornix rats had similar outward segments, the return paths of the fimbria-fornix rats were significantly slower, more circuitous, and more variable compared with that of the control rats. This result was also independent of testing in light or dark conditions. The lack of dependence on allothetic cues suggests that rats employ dead reckoning navigational strategies to initiate the homeward portion of exploratory movements. Methods to quantify exploratory behavior in terms of velocity and angular components provide an assessment of control behavior and the assessment of the behavior of rats with hippocampal formation damage that is easy to implement.     

Home bases formed to visual cues but not to self-movement (dead reckoning) cues in exploring hippocampectomized rats

Spatial theory proposes that the hippocampus contributes to exploratory behavior allowing animals to acquire information about their environment. In the present study, the exploratory movements of control rats, bulbectomized (anosmic) rats and hippocampectomized rats using the neurotoxin N-methyl-D-aspartate (NMDA) were monitored on a large circular table without walls and around which visual cues were manipulated. The rats displayed organized spatial behavior in that they developed home bases, one or more places operationally defined as those in which they spent a preponderance of time, in which they moved slowly, and to which they returned after excursions. Control rats and hippocampectomized rats were similar in that they established home bases: (i) adjacent to a proximal stable or moving visual landmark; (ii) in relation to more distant visual room cues; and (iii) in relation to contextually conditioned visual cues. Nevertheless, in exploratory tests given under infrared light, a wavelength to which rats are insensitive, control rats and bulbectomized rats established one or more home bases that were not dependent upon surface (e.g. olfactory) cues, whereas home base behavior was absent/fragmented in hippocampectomized rats. Thus, exploratory behavior, as exemplified by home base behavior, is organized in control and hippocampectomized rats in relation to visual cues, but is not organized in hippocampectomized rats when visual cues are absent. This result is discussed in relation to the idea that the hippocampus contributes to spatial behavior that is dependent upon guidance (dead reckoning) derived from self-movement cues.     

Effects of post-training lesions in the hippocampus and the parietal cortex on idiothetic information processing in the rat

Dead reckoning can be defined as the ability to navigate using idiothetic information based on self-movement cues without using allothetic information such as environmental cues. In the present study, we investigated the effects of hippocampal and parietal cortex lesions on homing behavior using dead reckoning in rats. Experimentally naive Wistar rats were trained with a homing task in which rats were required to take a food pellet from a cup in the arena and to return home with the pellet. After training, rats were divided into a control (CONT) group (n = 16), hippocampal lesioned (HIPP) group (n = 16), and parietal cortex lesioned (PARC) group (n = 16), and rats in the lesioned groups underwent surgery. After surgery, Test 1 (with four cups) and Test 2 (with one cup but the outgoing path was diverted by a barrier) were conducted. The HIPP group showed severe impairment in homing, but the performance of the PARC group did not differ from that of the CONT group. HIPP rats either approached wrong doors or ate the pellet in the arena. Circular statistics showed that homing directions of CONT and PARC rats showed concentration towards home, whereas those of HIPP rats did not. Our results exhibiting HIPP rats' failure in homing agree with many previous studies, but the results obtained from PARC rats were different from previous studies. These results indicate that the intact hippocampus is important for dead reckoning, but the role of the parietal cortex in dead reckoning is still not clear.     

Dead reckoning (path integration) requires the hippocampal formation: evidence from spontaneous exploration and spatial learning tasks in light (allothetic) and dark (idiothetic) tests.

Animals navigate using cues generated by their own movements (self-movement cues or idiothetic cues), as well as the cues they encounter in their environment (distal cues or allothetic cues). Animals use these cues to navigate in two different ways. When dead reckoning (deduced reckoning or path integration), they integrate self-movement cues over time to locate a present position or to return to a starting location. When piloting, they use allothetic cues as beacons, or they use the relational properties of allothetic cues to locate places in space. The neural structures involved in cue use and navigational strategies are still poorly understood, although considerable attention is directed toward the contributions of the hippocampal formation (hippocampus and associated pathways and structures, including the fimbria-fornix and the retrosplenial cortex). In the present study, using tests in allothetic and idiothetic paradigms, we present four lines of evidence to support the hypothesis that the hippocampal formation plays a central role in dead reckoning. (1) Control but not fimbria-fornix lesion rats can return to a novel refuge location in both light and dark (infrared) food carrying tasks. (2). Control but not fimbria-fornix lesion rats make periodic direct high velocity returns to a starting location in both light and dark exploratory tests. Control but not fimbria-fornix rats trained in the light to carry food from a fixed location to a refuge are able to maintain accurate outward and homebound trajectories when tested in the dark. (3). Control but not fimbria-fornix rats are able to correct an outward trajectory to a food source when the food source is moved when allothetic cues are present. These, tests of spontaneous exploration and foraging suggest a role for the hippocampal formation in dead reckoning.     

Rats can track odors, other rats, and themselves: implications for the study of spatial behavior

In order to demonstrate that rats solve dead reckoning (path integration) tasks in which they return to a starting location using self-movement (idiothetic) cues, it is necessary to remove external (allothetic) cues. Odor cues, especially those generated by a rat on a single passage, are difficult to control and they can potentially serve as a cue to guide a homeward trip. Because it is presently unknown whether rats can track the cues that they themselves leave, as opposed to the odor trails left by other rats, we investigated this question in the present study. A tracking task was used in which rats: (1) followed a scented string from a refuge to obtain a food pellet located on a large circular table; (2) followed odors left on the table; (3) followed odors left by the passage of another rat; or (4) followed odors left by themselves. Groups of rats were presented with strings scented with either the rat's own odor (Group Own), a conspecific's odor (Group Other), or another scent, vanilla (Group Vanilla). After training, a series of discrimination tests were given to determine the nature of the stimulus that controls scent tracking. The results indicated that Own, Other, and Vanilla groups were equally proficient in discriminating and following their respective odors. The rats were also able to follow odor trails on the table surface as well as a trail left by the single passage of another rat or their own passage. This is the first study to demonstrate that rats can discriminate between conspecific odors and their own odor left during a single passage. The results are discussed in relation to their implications for experimental methodology and olfactory contributions to spatial navigation in general and dead reckoning in particular.     

Limbic system structures differentially contribute to exploratory trip organization of the rat

The role of limbic system structures in spatial orientation continues to be debated. The hippocampus (HPC) has been implicated in encoding symbolic representations of environments (i.e., cognitive map), whereas entorhinal cortex (EC) function has been implicated in self‐movement cue processing (i.e., dead reckoning). These distinctions largely depend on the electrophysiological characteristics of cells within these regions and behavioral tasks that typically fail to dissociate environmental and self‐movement cue processing. Topographic and kinematic characteristics of exploratory trip organization have been shown to differentially depend on environmental and self‐movement cue processing. The present study examines the effects of either HPC or EC lesions on exploratory trip organization under varying lighting conditions. HPC lesions selectively impaired all measures of performance under dark conditions, but spared all measures of performance under light conditions. EC lesions impaired kinematic measures related to distance estimation under all conditions and impaired all measures of performance under light conditions. These results provide evidence that the HPC is involved in processing self‐movement cues but not environmental cues, and EC is involved in processing distance estimates generated from either self‐movement or environmental cues. These observations provide further support for serial processing of self‐movement cues through limbic system structures that converge on the HPC. © 2012 Wiley Periodicals, Inc.     

Impairment and recovery on a food foraging task following unilateral vestibular deafferentation in rats

It has been suggested that the vestibular system may contribute to the development of higher cognitive function, especially spatial learning and memory that uses idiothetic cues (e.g., dead reckoning). However, few studies have been done using behavioral tasks that could potentially separate the animals' ability for dead reckoning from piloting. The food foraging task requires the animal to continuously monitor and integrate self-movement cues and generate an accurate return path. It has been shown that bilateral vestibular-lesioned rats were impaired on this task. The present study used the same task to further examine the contribution of vestibular information to spatial navigation by comparing unilateral and bilateral lesions and by testing the animals at different time points following the lesion. The results demonstrated that animals with unilateral vestibular deafferentation were impaired in performing the task in the dark at 3 months after the lesion, and this impairment disappeared at 6 months after the lesion. This supports the notion that vestibular information contributes to dead reckoning and suggests possible recovery of function over time after the lesion. Animals with bilateral vestibular deafferentation were not able to be tested on the foraging task because they exhibited behavior distinct from the unilateral-lesioned animals, with significant hesitation in leaving their home cage for as long as 6 months after the lesion.     

Hippocampectomized rats are impaired in homing by path integration

Theoretical, behavioral, and electrophysiologic evidence suggests that the hippocampal formation may play a role in path integration, a form of spatial navigation in which an animal can return to a starting point by integrating self-movement cues generated on its outward journey. The present study examined whether the hippocampus (Ammon's horn and the dentate gyrus) is involved in this form of spatial behavior. Control rats and rats with selective ibotenic acid lesions of the hippocampus were tested in a foraging task in which they retrieved large food pellets from an open field, which when found, they carried to a refuge for consumption. The experiments measured the rats' homing accuracy, returning to the starting location, under conditions in which visual, surface, and self-movement cues; surface and self-movement cues; or only self-movement cues were available. Although both control rats and rats without a hippocampus could use visual and surface cues, only control rats appeared to be able to use self-movement cues. The finding that hippocampal rats are impaired under conditions requiring the use of self-movement cues suggests that the hippocampus plays an essential role in path integration.     

Movements of exploration intact in rats with hippocampal lesions

Prompted by the theoretical prediction that damage to the hippocampus should abolish exploratory behavior, the present study examined exploratory movements in control rats and rats with hippocampal lesions produced with the neurotoxin N-methyl d-aspartate (NMDA). In four daily 30-min sessions, control and hippocampal rats were exposed to an open circular table under room lighting. Both control and hippocampal rats spent a majority of time near, and organized trips away from, a portion of the table (home base) near a large cue placed proximal to the table. On Day 1, control and HPC rats made equal numbers of head orientations and a comparable number of trips, featuring equal travel distance and numbers of stops. By Day 4, dwell times near the home base increased and other movements decreased in the control rats but the activity profile of Day 1 persisted in the hippocampal rats. The high degree of similarity in behavior between hippocampal and control rats on Day 1 and the persistence of this behavior in hippocampal rats on Day 4 suggests that the hippocampus is not necessary for the display of normal exploratory movements per se. The absence of habituation of exploration in hippocampal rats is discussed in relation to contemporary theories of hippocampal function.     

Calibrating space: exploration is important for allothetic and idiothetic navigation

Allothetic and idiothetic navigation strategies rely on very different cues and computational procedures. Allothetic navigation uses the relationships between external cues (visual, auditory, and olfactory) and mapping or geometrical calculations to locate places. Idiothetic navigation relies on cues generated by self-movement (proprioceptive cues or cues from optic, auditory, and olfactory flow, or efference copy of motor commands) and path integration to locate a present location and/or a starting point. Whereas it is theorized that exploratory behavior is used by animals to create a central representation of allothetic cues, it is unclear whether exploration plays a role in idiothetic navigation. Computational models suggest that either a reference frame, calibrated by exploration, or vector addition, without reference to exploration, could support path integration. The present study evaluated the contribution of exploration in these navigation strategies by comparing its contribution to the solution of both allothetic and idiothetic navigation problems. In two experiments, rats were trained to forage on an open table for large food pellets, which they then carried to a refuge to eat. Once trained, they were given probe trials from novel locations in either normal light, which permits the use of allothetic cues, or in infrared light, which requires the use of idiothetic cues. When faced with a new problem in either lighting condition, the rats first explored the foraging table before navigating directly home with the food. That exploration is equally important for allothetic and idiothetic navigation, suggests that both navigation strategies require a calibrated representation of the environment.     

Long‐term deficits on a foraging task after bilateral vestibular deafferentation in rats

Animal studies have shown that bilateral vestibular deafferentation (BVD) causes deficits in spatial memory that may be related to electrophysiological and neurochemical changes in the hippocampus. Recently, human studies have also indicated that human patients can exhibit spatial memory impairment and hippocampal atrophy even 8–10 yr following BVD. Our previous studies have shown that rats with unilateral vestibular deafferentation (UVD) showed an impairment at 3 months after the surgery on a food foraging task that relies on hippocampal integration of egocentric cues, such as vestibular information; however, by 6 months postop, they showed a recovery of function. By contrast, the long‐term effects of BVD on spatial navigation have never been well studied. In this study, we tested BVD or sham rats on a food foraging task at 5 months postop. Under light conditions, BVD rats were able to use visual cues to guide themselves home, but did so with a significantly longer homing time. However, in darkness, BVD rats were severely impaired in the foraging task, as indicated by a significantly longer homing distance and homing time, with more errors and larger heading angles when compared with sham rats. These results suggest that, unlike UVD, BVD causes long‐term deficits in spatial navigation that are unlikely to recover, even with repeated T‐maze training. © 2008 Wiley‐Liss, Inc.     

Functional asymmetry of left and right avian piriform cortex in homing pigeons' navigation

It has been shown that homing pigeons rely on olfactory cues to navigate over unfamiliar areas and that any kind of olfactory impairment produces a dramatic reduction of navigational performance from unfamiliar sites. The avian piriform cortex is the main projection field of olfactory bulbs and it is supposed to process olfactory information; not surprisingly bilateral lesions to this telencephalic region disrupt homing pigeon navigation. In the present study, we attempted to assess whether the left and right piriform cortex are differentially involved in the use of the olfactory navigational map. Therefore, we released from unfamiliar locations pigeons subjected, when adult, to unilateral ablation of the piriform cortex. After being released, the pigeons lesioned to the right piriform cortex orientated similarly to the intact controls. On the contrary, the left lesioned birds were significantly more scattered than controls, showing a crucial role of the left piriform cortex in processing the olfactory cues needed for determining the direction of displacement. However, both lesioned groups were significantly slower than controls in flying back to the home loft, showing that the integrity of both sides of the piriform cortex is necessary to accomplish the whole homing process.     

Hippocampal damage produces retrograde but not anterograde amnesia for a cued location in a spontaneous exploratory task in rats

Performance in several memory tasks is known to be unaffected by hippocampal damage sustained before learning, but is severely disrupted if the same damage occurs after learning. Memories for preferred locations, or home bases, in exploratory tasks can be formed by rats with hippocampal damage, but it is unknown if the memory for a home base survives hippocampal damage. To examine this question, for 30 min each day for five consecutive days, rats explored a circular open field containing one local cue. By Day 5 the rats preferentially went directly to that location, spent the majority of their time at that location, made rapid direct trips to that location when returning from an excursion and so demonstrated that the location was a home base. Memory for the cued location was examined after a 24 h or 14‐day interval with the cue removed. In Experiments 1 and 2, control rats and rats with prior N‐methyl‐D ‐aspartic acid hippocampal lesions demonstrated memory of the home base location by making direct trips to that location. In Experiment 3, rats that had first explored the open field and cue and then received hippocampal lesions showed no memory for the cued location. The absence of anterograde impairment vs. the presence of retrograde impairment for memory of a spatial home base confirms a role for the hippocampus in the retention of spatial memory acquired during exploration. © 2009 Wiley‐Liss, Inc.     

Otolithic information is required for homing in the mouse

Navigation and the underlying brain signals are influenced by various allothetic and idiothetic cues, depending on environmental conditions and task demands. Visual landmarks typically control navigation in familiar environments but, in the absence of landmarks, self‐movement cues are able to guide navigation relatively accurately. These self‐movement cues include signals from the vestibular system, and may originate in the semicircular canals or otolith organs. Here, we tested the otolithic contribution to navigation on a food‐hoarding task in darkness and in light. The dark test prevented the use of visual cues and thus favored the use of self‐movement information, whereas the light test allowed the use of both visual and non‐visual cues. In darkness, tilted mice made shorter‐duration stops during the outward journey, and made more circuitous homeward journeys than control mice; heading error, trip duration, and peak error were greater for tilted mice than for controls. In light, tilted mice also showed more circuitous homeward trips, but appeared to correct for errors during the journey; heading error, trip duration, and peak error were similar between groups. These results suggest that signals from the otolith organs are necessary for accurate homing performance in mice, with the greatest contribution in non‐visual environments. © 2015 Wiley Periodicals, Inc.     

Navigation‐induced ZENK expression in the olfactory system of pigeons (Columba livia)

A large body of evidence indicates that pigeons use olfactory cues to navigate over unfamiliar areas with a differential contribution of the left and right hemispheres. In particular, the right nostril/olfactory bulb (OB) and left piriform cortex (Cpi) have been demonstrated to be crucially involved in navigation. In this study we analysed behaviour‐induced activation of the olfactory system, indicated by the expression of the immediate early gene ZENK, under different homing conditions. One experimental group was released from an unfamiliar site, the second group was transported to the unfamiliar site and back to the loft, and the third group was released in front of the loft. To evaluate the differential contribution of the left and/or right olfactory input, the nostrils of the pigeons were either occluded unilaterally or not. Released pigeons revealed the highest ZENK cell density in the OB and Cpi, indicating that the olfactory system is activated during navigation from an unfamiliar site. The groups with no plug showed the highest ZENK cell density, supporting the activation of the olfactory system probably being due to sensory input. Moreover, both Cpis seem to contribute differently to the navigation process. Only occlusion of the right OB resulted in a decreased ZENK cell expression in the Cpi, whereas occlusion of the left nostril had no effect. This is the first study to reveal neuronal activation patterns in the olfactory system during homing. Our data show that lateralized processing of olfactory cues is indeed involved in navigation over unfamiliar areas.     

Long-Range Respiratory and Theta Oscillation Networks Depend on Spatial Sensory Context

Neural oscillations can couple networks of brain regions, especially at lower frequencies. The nasal respiratory rhythm, which elicits robust olfactory bulb oscillations, has been linked to episodic memory, locomotion, and exploration, along with widespread oscillatory coherence. The piriform cortex is implicated in propagating the olfactory-bulb-driven respiratory rhythm, but this has not been tested explicitly in the context of both hippocampal theta and nasal respiratory rhythm during exploratory behaviors. We investigated systemwide interactions during foraging behavior, which engages respiratory and theta rhythms. Local field potentials from the olfactory bulb, piriform cortex, dentate gyrus, and CA1 of hippocampus, primary visual cortex, and nasal respiration were recorded simultaneously from male rats. We compared interactions among these areas while rats foraged using either visual or olfactory spatial cues. We found high coherence during foraging compared with home cage activity in two frequency bands that matched slow and fast respiratory rates. Piriform cortex and hippocampus maintained strong coupling at theta frequency during periods of slow respiration, whereas other pairs showed coupling only at the fast respiratory frequency. Directional analysis shows that the modality of spatial cues was matched to larger influences in the network by the respective primary sensory area. Respiratory and theta rhythms also coupled to faster oscillations in primary sensory and hippocampal areas. These data provide the first evidence of widespread interactions among nasal respiration, olfactory bulb, piriform cortex, and hippocampus in awake freely moving rats, and support the piriform cortex as an integrator of respiratory and theta activity.SIGNIFICANCE STATEMENT Recent studies have shown widespread interactions between the nasally driven respiratory rhythm and neural oscillations in hippocampus and neocortex. With this study, we address how the respiratory rhythm interacts with ongoing slow brain rhythms across olfactory, hippocampal, and visual systems in freely moving rats. Patterns of network connectivity change with behavioral state, with stronger interactions at fast and slow respiratory frequencies during foraging as compared with home cage activity. Routing of interactions between sensory cortices depends on the modality of spatial cues present during foraging. Functional connectivity and cross-frequency coupling analyses suggest strong bidirectional interactions between olfactory and hippocampal systems related to respiration and point to the piriform cortex as a key area for mediating respiratory and theta rhythms.     

Voles scale locomotion to the size of the open-field by adjusting the distance between stops: a possible link to path integration

In this study we show that social voles (Microtus socialis guentheri) preserve the same level of activity and spatio-temporal organization of behavior whether exploring a small (1 x 1 m) or a large (2 x 2 m) open field. In each open field, a vole established a home base from which it set on to round-trips of exploration; taking fewer but longer trips in the large open field, compared with more frequent but shorter trips in the small open field. Each trip comprised bouts of progression (locomotion) interrupted by stops. The number of stops per trip was the same for both large open field (longer trips) and small open field (shorter trips), and achieved by scaling the distance between stops according to the size of the open field. Voles traveled more along the walls in the large compared with the small open field. These adjustments in locomotor behavior to open field size were observed immediately after the voles were introduced into the arena, indicating that the perceived distances available for locomotion were identified by the voles immediately at the beginning of exploration. It is suggested that these properties of spontaneous exploration are an expression of navigation using visual landmarks and path integration.     

The point of entry contributes to the organization of exploratory behavior of rats on an open field: an example of spontaneous episodic memory

The exploratory behavior of rats on an open field is organized in that animals spend disproportionate amounts of time at certain locations, termed home bases, which serve as centers for excursions. Although home bases are preferentially formed near distinctive cues, including visual cues, animals also visit and pause and move slowly, or linger, at many other locations in a test environment. In order to further examine the organization of exploratory behavior, the present study examined the influence of the point of entry on animals placed on an open field table that was illuminated either by room light or infrared light (a wavelength in which they cannot see) and near which, or on which, distinctive cues were placed. The main findings were that in both room light and infrared light tests, rats visited and lingered at the point of entry significantly more often than comparative control locations. Although the rats also visited and lingered in the vicinity of salient visual cues, the point of entry still remained a focus of visits. Finally, the preference for the point of entry increased as a function of salience of the cues marking that location. That the point of entry influences the organization of exploratory behavior is discussed in relation to the idea that the exploratory behavior of the rat is directed toward optimizing security as well as forming a spatial representation of the environment.     

Similar development of cued and learned home bases in control and hippocampal-damaged rats in an open field exploratory task

Spatial behavior was examined in control rats and rats with neurotoxic-induced damage of the hippocampus in an open field "exploratory" task. In Experiment 1, rats were placed on a large circular table for 30 min for four consecutive days with a short wall adjacent to the table and a large black box near the edge of the table diametrically opposite to the wall. On the fifth day, rats were given a probe test during which both cues were removed. Over the training exposures both control and hippocampal-damaged rats formed "home bases," operationally defined as places where the rats preferentially stopped and spent time, near the cues. When the cues were removed on the probe day, both groups visited, stopped near, and spent time at places adjacent to the cues' previous location. In Experiment 2, rats were given a similar training protocol, but only a single cue was used, which was a small box placed directly on the table that did not block visibility of the entire room. On the fifth day, the box was moved to the other end of the table. Despite the presence of a cued home base, control and hippocampal-damaged rats remembered the original location of the home base. The results are discussed in relation to the comparative task demands of formal and informal test procedures and with respect to their relevance to understanding the neural basis of spatial behavior.     

Homing with locale, taxon, and dead reckoning strategies by foraging rats: sensory hierarchy in spatial navigation.

Studies on foraging rats suggest that they can use visual, olfactory, and self-movement cues for spatial guidance, but their relative reliance on these different cues is not well understood. In the present study, rats left a hidden refuge to search for a large food pellet located somewhere on a circular table, and the accuracy with which they returned to the refuge with the food pellet was measured. Cue use was manipulated by administering probe trials from novel locations, blindfolding, moving the home cage relative to the table, rotating the table and using combinations of these manipulations. When visual cues were available and a consistent starting location used, a visual strategy dominated performance. When blindfolded, the rats used olfactory cues from the surface of the table and from the starting hole. When olfactory stimuli were made uninformative, by changing the starting hole and rotating the table, the rats still homed accurately, suggesting they used self-movement cues. In a number of cue combinations, in which cues gave conflicting information, performance degraded. The results suggest that rats display a hierarchical preference in using visual, olfactory and self-movement cues while at the same time being able to reaffirm or switch between various cue combinations. The results are discussed in relation to ideas concerning the neural basis of spatial navigation.