Comparison of ventral subicular and hippocampal neuron spatial firing patterns in complex and simplified environments.

Activity from ventral subicular and hippocampal CA1 neurons was recorded in rats exploring a 4-arm radial maze in which the local and distal cues could be manipulated. Cells from both regions exhibited place fields, although ventral subicular neurons had larger fields than hippocampal cells. Rotation of the local and distal cues in opposite directions produced movement of the place fields in either direction or a complete change in firing pattern. Simplifying the environment also produced changes in place field location. Despite similarities between regions, subiculum fields decreased in size whereas hippocampal fields increased in the simple environment. These findings suggest that subicular cells may receive converging input from several hippocampal neurons and code more complex configurations of the cues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brain aging: impaired coding of novel environmental cues

Studies of the spatial memory capacities of aged animals usually focus on performance during the learning of new environments. By contrast, efforts to characterize age-related alterations in spatial firing information processing by hippocampal neurons typically use an environment that is highly familiar to the animals. In the present study we compared the firing properties of hippocampal neurons in young adult and aged rats as they acquired spatial information about new environmental cues. Hippocampal complex spike cells were recorded while rats performed a radial arm maze task in a familiar environment and then recorded again after many of the spatial cues were changed. After the change in the environment, in aged rats 35-42% of place fields retained their original shape and location with respect to the maze center, although they usually rotated to another arm. By contrast, all place fields in young animals either disappeared or appeared in a new location. Some of the new place fields appeared in the new environment during the first 5 min of exploration, whereas others needed more than 30 min to develop fully. In the familiar environment spatial selectivity of place cells was similar in young and aged rats. By contrast, when rats were placed into a new environment, spatial selectivity decreased considerably in aged memory-impaired rats compared with that of young rats and aged rats with intact memory performance.     

Cues that hippocampal place cells encode: dynamic and hierarchical representation of local and distal stimuli

Hippocampal place fields were recorded as rats explored a four-arm radial maze surrounded by curtains holding distal stimuli and with distinct local tactile, olfactory, and visual cues covering each arm. Systematic manipulations of the individual cues and their interrelationships showed that different hippocampal neurons encoded individual local and distal cues, relationships among cues within a stimulus set, and the relationship between the local and distal cues. Double rotation trials, which maintained stimulus relationships within distal and local cue sets, but altered the relationship between them, often changed the responses of the sampled neural population and produced new representations. After repeated double rotation trials, the incidence of new representations increased, and the likelihood of a simple rotation with one of the cue sets diminished. Cue scrambling trials, which altered the topological relationship within the local or distal stimulus set, showed that the cells that followed one set of controlled stimuli responded as often to a single cue as to the constellation. These cells followed the single cue when the stimulus constellation was scrambled, but often continued firing in the same place when the stimulus was removed or switched to respond to other cues. When the maze was surrounded by a new stimulus configuration, all of the cells either developed new place fields or stopped firing, showing that the controlled stimuli had persistent and profound influence over hippocampal neurons. Together, the results show that hippocampal neurons encode a hierarchical representation of environmental information.     

Partial hippocampal kindling affects retention but not acquisition and place but not cue tasks on the radial arm maze

The performance of rats that were partially kindled in the hippocampus was assessed on an 8-arm radial arm maze with 4 baited arms. In rats first trained and then kindled, deficits were found on a place task in which rats reached the goal arms of the maze using salient extramaze spatial cues, but not on an intramaze cue task in which rats reached the goal arms using salient intramaze cues. Acquisition of a new place task on the maze was not different between kindled and control rats. In conclusion, partial hippocampal kindling disrupted the retention but not the acquisition of a spatial or place task; retention of a nonspatial cue task was not disrupted.     

Chronic stress impairs rat spatial memory on the Y maze, and this effect is blocked by tianeptine treatment.

Chronic restraint stress causes significant dendritic atrophy of CA3 pyramidal neurons that reverts to baseline within a week. Therefore, the authors assessed the functional consequences of this atrophy quickly (within hours) using the Y maze. Experiments 1–3 demonstrated that rats relied on extrinsic, spatial cues located outside of the Y maze to determine arm location and that rats with hippocampal damage (through kainic acid, colchicine, or trimethyltin) had spatial memory impairments. After the Y maze was validated as a hippocampally relevant spatial task, Experiment 4 showed that chronic restraint stress impaired spatial memory performance on the Y maze when rats were tested the day after the last stress session and that tianeptine prevented the stress-induced spatial memory impairment. These data are consistent with the previously demonstrated ability of tianeptine to prevent chronic stress-induced atrophy of the CA3 dendrites. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brain aging: changes in the nature of information coding by the hippocampus

Advanced age in rats is associated with a decline in spatial memory capacities dependent on hippocampal processing. As yet, however, little is known about the nature of age-related alterations in the information encoded by the hippocampus. Young rats and aged rats identified as intact or impaired in spatial learning capacity were trained on a radial arm maze task, and then multiple parameters of the environmental cues were manipulated to characterize the changes in firing patterns of hippocampal neurons corresponding to the presence of particular cues or the spatial relationships among them. The scope of information encoded by the hippocampus was reduced in memory-impaired aged subjects, even though the number of neurons responsive to salient environmental cues was not different from that in young rats. Furthermore, after repeated manipulations of the cues, memory-intact aged rats, like young rats, altered their spatial representations, whereas memory-impaired aged rats showed reduced plasticity of their representation throughout testing. Thus changes in hippocampal memory representation associated with aging and memory loss can be characterized as a rigid encoding of only part of the available information.     

Hippocampal place fields are altered by the removal of single visual cues in a distance-dependent manner.

Hippocampal CA3 cells were recorded in male Long-Evans rats that explored a square recording chamber. Three of the 4 chamber walls held a rectangular cue card, each of different size. Rotating the set of cue cards rotated the location of the place fields. Place fields were common close to the walls of the recording chamber, particularly the walls with cues. When single cues were removed, the spatial information content decreased but returned to baseline levels when the cue was replaced. When a cue near a place field was removed, the place field firing rate and area decreased; when a distant cue was removed, firing rate and area increased. Thus, removing single visual cues predictably and reversibly altered hippocampal place fields. Together, the results suggest that hippocampal neurons may optimize the encoding of visual information and are consistent with a distance-encoding hypothesis of CA3 network function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial memory deficits in a virtual radial arm maze in amnesic participants with hippocampal damage.

Extensive research with laboratory animals indicates that the hippocampus is crucial for the formation and use of spatial memory. Hippocampal lesions in rodents impair spatial memory on radial arm maze tasks. It is unknown whether amnesic patients with hippocampal damage would exhibit similar impairments on a virtual version of a radial arm maze. To evaluate the importance of the hippocampus in spatial learning and memory, we tested amnesic participants with hippocampal damage in a virtual radial arm maze environment. The virtual radial arm maze required participants to learn and remember 4 rewarded arms of 8 total arms. Spatial learning and memory were assessed using the participants' ability to use salient distal cues in the virtual room to remember the 4 rewarded arms. Amnesic participants' latencies were longer and distance traveled was greater to the rewarded arms compared with nonamnesic participants. Amnesic participants made more errors than nonamnesic participants by either entering nonrewarded arms or by revisiting previously entered arms. These data are analogous to previous animal research. Overall, the human hippocampus is necessary for spatial memory and navigation in a virtual radial arm maze task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

H-7 stimulates desmosome formation and inhibits growth in KB oral carcinoma cells

Groups of old and young rats were administered three tests of spatial learning and memory that are known to be sensitive to hippocampal dysfunction: the radial arm maze (RAM), spatial non-matching-to-sample (SNMTS), and a spatial vs. local cue-preference task. Old rats performed worse than young rats on the RAM and SNMTS tasks; on the cue-preference task, young rats were biased to use spatial cues, whereas old rats exhibited strong preferences for distinct, local cues. Peripheral injections of glucose (100 mg/kg) improved performance by old rats on the RAM and SNMTS, which correlated with measures of glucose metabolism. Glucose treatment did not affect old rats performance on the cue-preference task. There was evidence that glucose-treatment improved performance of young rats in the RAM test, but not the other tests. The results extend the range of tasks on which glucose-induced cognitive enhancement has been demonstrated in aged rats, and provides further evidence that memory loss resulting from hippocampal dysfunction is especially amenable to glucose treatment.     

Radial-arm maze behavior by rats with dorsal hippocampal lesions: Effects of cuing.

In 4 experiments with 180 male Wistar and Long-Evans rats, Ss with bilateral dorsal hippocampal lesions were impaired when tested on standard (noncued) versions of the radial-arm maze, but other hippocampal groups performed almost as well as cortical and operated control groups when salient visual cues were added to each arm. Preoperative training on the noncued, but not the cued, maze interfered with the benefits of postoperatively cuing hippocampal groups. Control groups performed equally well under all cuing and training conditions. Procedures that eliminated response sequencing did not affect performance of hippocampal or control groups. Results are interpreted as reflecting hippocampal involvement in mediating spatial cues, but not necessarily along the lines predicted by cognitive map theory. It is suggested that deficits of animals with hippocampal lesions represent 1 manifestation of a general impairment in processing information. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of excitotoxic lesions centered on the hippocampus or perirhinal cortex in object recognition and spatial memory tasks.

Rats with bilateral ibotenic acid lesions centered on the hippocampus (HPC) or perirhinal cortex (PRC) and sham-operated controls were tested in a series of object recognition and spatial memory tasks. Both HPC and PRC rats displayed reduced habituation in a novel environment and were impaired in an object-location task. HPC rats were severely impaired in both the reference and working-memory versions of the water maze and radial arm maze tasks. In contrast, although PRC rats displayed mild deficits in the reference memory version of the water maze and radial arm maze tasks, they were markedly impaired in the working-memory version of both the tasks. These findings demonstrate that under certain conditions both the HPC and PRC play a role in the processing of spatial memory. Further investigation of these conditions will provide important new insights into the role of these structures in memory processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Where am I? Distal cues use requires sensitivity to start location change in the rat.

Place learning is impaired when a single plus maze is moved between adjacent locations 33-120 cm apart. This maze translation creates distinct start locations but maintains a single goal location with respect to distal cues. Hippocampal cell recording data suggest the majority of place fields are tied to apparatus boundaries, not to distal cues, when an apparatus is moved these distances to the left or right. Thus, rats may fail to appreciate the existence of multiple start locations with respect to distal cues when the maze is moved in this way and their start location on the surface is constant. Performance on the single plus maze problem was improved when texture cues were correlated with different start locations. Place learning was supported when multiple start locations were provided on a single large surface (double plus maze), even though rats did not explore the entire surface. Place learning was also supported when random extensions were added to a double plus maze such that start locations, relative to surface boundaries, were not informative as to goal location. This outcome suggests sensitivity to multiple start locations is required for distal cue use in translational place problems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Both anteromedial and anteroventral thalamic lesions impair radial-maze learning in rats.

Disruption to the anterior thalamus (AT) may be an important factor in diencephalic amnesia. Rats with small lesions of the anteromedial (AM) or anteroventral (AV) nucleus showed persistent working-memory and reference-memory deficits in a 12-arm radial maze, although they were comparable to controls during the early part of training. The only activity difference in the maze was that lesioned rats failed to run more slowly when revisiting a baited arm. For all groups, both working and reference memory were impaired after extramaze cues were removed; removal of intramaze cues further impaired performance relative to the original conditions. These findings suggest the AT makes a distinct contribution to mnemonic functions, probably as part of an integrated system involving limbic cortex and the hippocampal formation, and that AT lesions produce a general rather than a specific deficit in spatial or working memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Entorhinal-perirhinal lesions impair performance of rats on two versions of place learning in the Morris water maze.

The effects of entorhinal–perirhinal lesions in rats were studied with 2 versions of a place learning task in the Morris water maze. These lesions impaired performance on a multiple-trial task (3 days of 6 trials and a probe trial). This assessment was followed by a task in which rats were repeatedly trained to find novel locations with a variable delay (30 sec or 5 min) imposed between each sample trial and retention test. Entorhinal–perirhinal damage produced a delay-dependent deficit in spatial memory: Rats with lesions were impaired at the 5-min delay relative to the control group and to their own performance at 30 sec. These findings are discussed in relationship to memory impairment after entorhinal damage and spatial learning deficits observed after hippocampal damage. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Glutamate receptor-mediated restoration of experience-dependent place field expansion plasticity in aged rats.

Place fields of hippocampal pyramidal cells expand asymmetrically when adult rats repeatedly follow the same route. This behaviorally induced expression of neuronal plasticity uses an NMDAR-dependent, LTP-like mechanism and could be used by hippocampal networks to store information. Aged spatial memory-impaired rats exhibit defective experience-dependent place field expansion plasticity. One possible explanation for this aged-associated deficit is alterations in glutamatergic function. In fact, both NMDAR- and AMPAR-mediated field excitatory postsynaptic potentials in CA1 decrease with aging. The current study investigated whether modulation of either AMPA or NDMA receptor activity could restore this experience-dependent plasticity by prolonging AMPAR activity with the ampakine CX516 and modulating the NMDAR with the noncompetitive antagonist memantine. The spatial firing characteristics of multiple CA1 pyramidal cells were monitored under both treatment conditions as aged rats repeatedly traversed a circular track. Compared to the saline baseline condition, acute administration of memantine, but not CX516, reinstated experience-dependent place field expansion. Taken together, these data suggest that pharmacological manipulation of the NMDAR can improve the function of hippocampal networks critical to optimal cognition in aging. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Superior colliculus and active navigation: role of visual and non-visual cues in controlling cellular representations of space

To begin investigation of the contribution of the superior colliculus to unrestrained navigation, the nature of behavioral representation by individual neurons was identified as rats performed a spatial memory task. Similar to what has been observed for hippocampus, many superior collicular cells showed elevated firing as animals traversed particular locations on the maze, and also during directional movement. However, when compared to hippocampal place fields, superior collicular location fields were found to be more broad and did not exhibit mnemonic properties. Organism-centered spatial coding was illustrated by other neurons that discharged preferentially during right or left turns made by the animal on the maze, or after lateralized sensory presentation of somatosensory, visual, or auditory stimuli. Nonspatial movement-related neurons increased or decreased firing when animals engaged in specific behaviors on the maze regardless of location or direction of movement. Manipulations of the visual environment showed that many, but not all, spatial cells were dependent on visual information. The majority of movement-related cells, however, did not require visual information to establish or maintain the correlates. Several superior collicular cells fired in response to multiple maze behaviors; in some of these cases a dissociation of visual sensitivity to one component of the behavioral correlate, but not the other, could be achieved for a single cell. This suggests that multiple modalities influence the activity of single neurons in superior colliculus of behaving rats. Similarly, several sensory-related cells showed dramatic increases in firing rate during the presentation of multisensory stimuli compared to the unimodal stimuli. These data reveal for the first time how previous findings of sensory/motor representation by the superior colliculus of restrained/anesthetized animals might be manifested in freely behaving rats performing a navigational task. Furthermore, the findings of both visually dependent and visually independent spatial coding suggest that superior colliculus may be involved in sending visual information for establishing spatial representations in efferent structures and for directing spatially-guided movements.     

Newborn organ weight and spontaneous hypertension: recombinant inbred strain study

This study investigated the effects of neonatal hippocampal ablation on the development of spatial learning and memory abilities in rats. Newborn rats sustained bilateral electrolytic lesions of the hippocampus or were sham-operated on postnatal day 1 (PN1). At PN20-25, PN50-55, or PN90-95, separate groups of rats were tested in a Morris water maze on a visible "cue" condition (visible platform in a fixed location of the maze), a spatial "place" condition (submerged platform in a fixed location), or a no-contingency "random" condition (submerged platform in a random location). Rats were tested for 6 consecutive days, with 12 acquisition trials and 1 retention (probe) trial per day. During acquisition trials, the rat's latency to escape the maze was recorded. During retention trials (last trial for each day, no escape platform available), the total time the rat spent in the probe quadrant was recorded. Data from rats with hippocampal lesions tested as infants (PN20-25) or as adults (PN50-55 and PN90-95) converged across measures to reveal that 1) spatial (place) memory deficits were evident throughout developmental testing, suggesting that the deficits in spatial memory were long-lasting, if not permanent, and 2) behavioral performance measures under the spatial (place) condition were significantly correlated with total volume of hippocampal tissue damage, and with volume of damage to the right and anterior hippocampal regions. These results support the hypothesis that hippocampal integrity is important for the normal development of spatial learning and memory functions, and show that other brain structures do not assume hippocampal-spatial memory functions when the hippocampus is damaged during the neonatal period (even when testing is not begun until adulthood). Thus, neonatal hippocampal damage in rats may serve as a rodent model for assessing treatment strategies (e.g., pharmacological) relevant to human perinatal brain injury and developmental disabilities within the learning and memory realm.     

The effect of excitotoxic lesions centered on the perirhinal cortex in two versions of the radial arm maze task.

Rats with bilateral ibotenic acid lesions centered on the perirhinal cortex and sham-operated controls were tested in 2 versions of a spatially guided radial arm maze task. Lesioned rats made significantly more errors and required more sessions to reach criterion relative to controls in the standard radial maze task. When they were tested in a delayed nonmatch to sample version of this task, lesioned rats made more errors during the predelay phase and at both the 30-s and 10-min delays of the postdelay phase. These findings provide further support for the hypothesis that the role of the perirhinal cortex in object recognition memory may include reference to some spatial aspect of the environment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampal place fields: relationship between degree of field overlap and cross-correlations within ensembles of hippocampal neurons

The capacity to record from multiple neurons in awake freely moving animals provides a means for characterizing organizational principles of place field encoding within ensembles of hippocampal neurons. In this study, cross-correlations between pairs of hippocampal place cells and degree of overlap between their respective place fields were analyzed during behavioral performance of delayed matching (DMS) or non-matching sample (DNMS) tasks, or while the same rats chased pellets in a different environment. The relationship between field overlap and cross-correlations of neural spike activity within ensembles was shown to be a positive, exponentially increasing, function. Place fields from the same neurons were markedly "remapped" between the Delay and Pellet-chasing tasks, with respect to physical location and size of fields. However individual pairs of place cells within each ensemble retained nearly the same degree of overlap and cross-correlation even though the spatial environment and the tasks differed markedly. This suggested that place cells were organized in functional "clusters" which exhibited the same inter-relations with respect to place field overlap and cross-correlations, irrespective of actual field of location. When cross-correlations between place cells were compared to placement of the array recording electrodes within the hippocampus, the strongest correlations were found along previously defined posterior-projecting fiber gradients between CA3 and CA1 subfields (Ishizuka et al. [1990], J Comp Neurol 295:580-623; Li et al. [1994] (J Comp Neurol 339:181-208). These findings suggest that the functional organization of place fields conforms to anatomical principles suspected to operate within hippocampal ensembles.     

A simple network model simulates hippocampal place fields: Parametric analyses and physiological predictions.

Hippocampal place cells may be the computational units of a neuronal cognitive mapping system. A network model trained to compute locations from distal cues simulated the defining properties of hippocampal place cells (i.e., place-specific activation). The model produced units with detailed properties of place cells, including multiple subfields, "silent" and "noisy" cells, fields that persisted after cue removal, and groups of simulated field that overlapped in multiple clusters. Quantitative variants of the model showed that different properties of the fields were influenced by the complexity of the visual input (the number of spatial cues), the available computational resources (the number of hidden units), and the output encoding used to represent location. The simulations provide a framework for testing relationships between place field properties, variations in spatial environments, and the integrity of the hippocampal system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)