Retrograde amnesia for spatial information: a dissociation between intra and extramaze cues following hippocampus lesions in rats

Several recent studies have shown a flat retrograde amnesia for spatial information following lesions to the hippocampus in rats and mice. However, the results of the present investigation demonstrate that in rats that presurgically learned a spatial reference memory task based on extramaze cues, a temporally graded retrograde amnesia is evident following lesions to the hippocampus (1, 16, 32 or 64 days after learning) if two conditions are met. First, that a wide range of retention intervals is used, and second, that independent groups of rats are tested, not a single group that learns different spatial discrimination tasks at different times (expt 1). The results of expt 2 show that the hippocampus does not serve as a consolidating mechanism when the spatial task learned presurgically is based on intramaze cues. Taken together, these results indicate that the hippocampus is critical for the storage and/or retrieval of spatial reference information that was learned up to 1 month before hippocampus damage; however, in the absence of the hippocampus, efficient retention can still occur provided that the spatial knowledge was learned in a simple associative manner.     

The interactions and dissociations of the dorsal hippocampus subregions: How the dentate gyrus, CA3, and CA1 process spatial information.

Several studies have demonstrated the significance of a spatial cognitive map and its role for guided and accurate navigation through the environment. Learning and recalling spatial knowledge depends upon proper topological and metric spatial information processing. The present objectives are to better characterize the role of the hippocampus for processing topological and metric spatial information. Rats with dorsal hippocampal subregional lesions (dDG, dCA3, dCA1) were tested on a previously established metric task and topological task. The results of the present study suggest that dCA1, but not dDG or dCA3, mediates topological memory. Furthermore, dDG, dCA3, and dCA1 mediate metric memory. Dorsal DG is required for spatial information processing via pattern separation or orthogonalization of sensory inputs to generate metric representations. Dorsal CA3 and dCA1 then receive these metric representations transmitted from dDG along the trisynaptic loop. The present data add to a growing body of literature suggesting a diversity of function among the hippocampal subregions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Unpacking the cognitive map: The parallel map theory of hippocampal function.

In the parallel map theory, the hippocampus encodes space with 2 mapping systems. The bearing map is constructed primarily in the dentate gyrus from directional cues such as stimulus gradients. The sketch map is constructed within the hippocampus proper from positional cues. The integrated map emerges when data from the bearing and sketch maps are combined. Because the component maps work in parallel, the impairment of one can reveal residual learning by the other. Such parallel function may explain paradoxes of spatial learning, such as learning after partial hippocampal lesions, taxonomic and sex differences in spatial learning, and the function of hippocampal neurogenesis. By integrating evidence from physiology to phylogeny, the parallel map theory offers a unified explanation for hippocampal function. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Memory and the hippocampus in food-storing birds: a comparative approach

Comparative studies provide a unique source of evidence for the role of the hippocampus in learning and memory. Within birds and mammals, the hippocampal volume of scatter-hoarding species that cache food in many different locations is enlarged, relative to the remainder of the telencephalon, when compared with than that of species which cache food in one larder, or do not cache at all. Do food-storing species show enhanced memory function in association with the volumetric enlargement of the hippocampus? Comparative studies within the parids (titmice and chickadees) and corvids (jays, nutcrackers and magpies), two families of birds which show natural variation in food-storing behavior, suggest that there may be two kinds of memory specialization associated with scatter-hoarding. First, in terms of spatial memory, several scatter-hoarding species have a more accurate and enduring spatial memory, and a preference to rely more heavily upon spatial cues, than that of closely related species which store less food, or none at all. Second, some scatter-hoarding parids and corvids are also more resistant to memory interference. While the most critical component about a cache site may be its spatial location, there is mounting evidence that food-storing birds remember additional information about the contents and status of cache sites. What is the underlying neural mechanism by which the hippocampus learns and remembers cache sites? The current mammalian dogma is that the neural mechanisms of learning and memory are achieved primarily by variations in synaptic number and efficacy. Recent work on the concomitant development of food-storing, memory and the avian hippocampus illustrates that the avian hippocampus may swell or shrivel by as much as 30% in response to presence or absence of food-storing experience. Memory for food caches triggers a dramatic increase in the total number of number of neurons within the avian hippocampus by altering the rate at which these cells are born and die.     

Memory for places: a navigational model in support of Marr's theory of hippocampal function

In this report we describe a model that applies Marr's theory of hippocampal function to the problem of map-based navigation. Like many others we attribute a spatial memory function to the hippocampus, but we suggest that the additional functional components required for map-based navigation are located elsewhere in the brain. One of the key functional components in this model is an egocentric map of space, located in the neocortex, that is continuously updated using ideothetic (self-motion) information. The hippocampus stores snapshots of this egocentric map. The modeled activity pattern of head direction cells is used to set the best egocentric map rotation to match the snapshots stored in the hippocampus, resulting in place cells with a nondirectional firing pattern. We describe an evaluation of this model using a mobile robot and demonstrate that with this model the robot can recognize an environment and find a hidden goal. This model is discussed in the context of prior experiments that were designed to discover the map-based spatial processing of animals. We also predict the results of further experiments.     

Memory for novel and familiar spatial and linguistic temporal distance information in hypoxic subjects

Hypoxia is known to cause damage to the hippocampus as well as memory impairments in humans. Subjects who have experienced a hypoxic episode and age-, gender-, and education-matched control subjects were tested for memory for spatial and linguistic temporal distance information using sentences and spatial locations. Each test contained a familiar component based on information that is meaningful and is thought to be stored as part of the knowledge system (prior knowledge) as well as a novel component based on new information. Subjects were presented a list of eight-word sentences or eight spatial locations (Xs) on a grid on a Macintosh computer and tested for memory for temporal distances. Temporal distance is defined as the number of items that occur between the two test items, in the study phase. Compared to control subjects, hypoxic subjects were impaired across all temporal distances on the novel spatial and linguistic tasks. As the temporal distance increased, hypoxic subjects showed some improvement in memory performance. In addition, memory of familiar temporal distance information was also assessed. Hypoxic subjects were impaired, compared to control subjects, for familiar temporal distance information. For hypoxic subjects there was a proportionally greater impairment for novel compared to familiar spatial and linguistic temporal distance information. There was a significant difference in their performance on the familiar temporal distance tasks compared to their performance on the novel tasks. Prior knowledge appears to attenuate the deficits seen in the familiar temporal distance tasks. It appears that hypoxia may cause more selective damage to the hippocampus and this damage is sufficient to produce profound memory impairments for primarily novel and less severe memory impairments for familiar spatial and linguistic temporal distance information.     

Functional differentiation along the anterior-posterior axis of the hippocampus in monkeys

We tested whether the primate hippocampus was functionally heterogenous along its anterior-posterior axis. Two monkeys were trained on both a spatial and nonspatial memory task and the incidence of spatial and nonspatial delay activity in the anterior, middle, and posterior hippocampus was noted. Spatial delay activity (activity in the delay period after the sample stimulus on the spatial memory task) was more common in the posterior than the anterior hippocampus, whereas nonspatial delay activity (activity in the delay period after the sample stimulus on the nonspatial memory task) was evenly distributed throughout the hippocampus. Furthermore, delay neurons in the anterior hippocampus exhibited scalloping delay activity, whereas those in the middle and posterior hippocampus did not. These findings suggest that the hippocampus is functionally heterogeneous and that the posterior regions may be more important for processing spatial information, whereas the anterior regions may be more important for directing or coding movements to points in space.     

Translocation of protein kinase Cγ occurs during the early phase of acquisition of food rewarded spatial learning.

This study describes the translocation of the brain specific protein kinase C gamma isoenzyme (PKCγ) in the hippocampus during food rewarded spatial learning. The holeboard test was used for spatial orientation, and immunoblot analysis was used for assessment of PKCγ in cytosolic, membrane-inserted and membrane-associated fractions. Membrane-associated PKCγ was increased during early acquisition of spatial learning, but not in a later phase of training. This transient and apparently temporary intracellular PKCγ translocation was only observed in the posterior but not in the anterior hippocampus, and was only detected within 10 min after termination of the learning trial. This study supports the idea that PKCγ is significantly involved in the biochemical events underlying learning and memory, notably during the period of novel information processing. The results further promote the hypothesis that the hippocampus is specifically involved in temporal information processing, which requires the engagement of PKCγ. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The photosensitivity dermatitis and actinic reticuloid syndrome (chronic actinic dermatitis) occurring in seven young atopic dermatitis patients

This study describes the translocation of the brain specific protein kinase C gamma isoenzyme (PKCgamma) in the hippocampus during food rewarded spatial learning. The holeboard test was used for spatial orientation, and immunoblot analysis was used for assessment of PKCgamma in cytosolic, membrane-inserted and membrane-associated fractions. Membrane-associated PKCgamma was increased during early acquisition of spatial learning, but not in a later phase of training. This transient and apparently temporary intracellular PKCgamma translocation was only observed in the posterior but not in the anterior hippocampus, and was only detected within 10 min after termination of the learning trial. This study supports the idea that PKCgamma is significantly involved in the biochemical events underlying learning and memory, notably during the period of novel information processing. The results further promote the hypothesis that the hippocampus is specifically involved in temporal information processing, which requires the engagement of PKCgamma.     

Recalling Spatial Information as a Component of Recently and Remotely Acquired Episodic or Semantic Memories: An fMRI Study.

Activations produced by the recall of episodic and semantic memories differing in spatial content and age were examined. Recall of recent episodic memories with differing spatial content activated the medial temporal lobes and the retrosplenial-posterior cingulate cortex-precuneus complex more than recall of recent semantic memories with similarly differing spatial content. Some of these differences related to the amount of spatial information recalled because spatially richer recent memories, regardless of whether they were episodic or semantic, activated the right posterior parahippocampal cortex, precuneus, and posterior parietal cortex more. This spatial effect was found to be independent of memory age for semantic memories, although some episodic-semantic memory differences, including one in the left hippocampus, were not age independent. Episodic-semantic memory recall activation differences are therefore probably a function of the amount recalled, memory age, and what is recalled, particularly with respect to spatial information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial learning deficits in mice with a targeted glucocorticoid receptor gene disruption

Previous studies in rats using the Morris water maze suggested that the processing of spatial information is modulated by corticosteroid hormones through mineralocorticoid and glucocorticoid receptors in the hippocampus. Mineralocorticoid receptors appear to be involved in the modulation of explorative behaviour, while additional activation of glucocorticoid receptors facilitates the storage of information. In the present study we used the water maze task to examine spatial learning and memory in mice homozygous and heterozygous for a targeted disruption of the glucocorticoid receptor gene. Compared with wild-type controls, homozygous and heterozygous mice were impaired in the processing of spatial but not visual information. Homozygous mutants performed variably during training, without specific platform-directed search strategies. The spatial learning disability was partly compensated for by increased motor activity. The deficits were indicative of a dysfunction of glucocorticoid receptors as well as of mineralocorticoid receptors. Although the heterozygous mice performed similarly to wild-type mice with respect to latency to find the platform, their strategy was more similar to that of the homozygous mice. Glucocorticoid receptor-related long-term spatial memory was impaired. The increased behavioural reactivity of the heterozygous mice in the open field points to a more prominent mineralocorticoid receptor-mediated function. The findings indicate that (i) the glucocorticoid receptor is of critical importance for the control of spatial behavioural functions, and (ii) mineralocorticoid receptor-mediated effects on this behaviour require interaction with functional glucocorticoid receptors. Until the development of site-specific, inducible glucocorticoid receptor mutants, glucocorticoid receptor-knockout mice present the only animal model for the study of corticosteroid-mediated effects in the complete absence of a functional receptor.     

Lesions of the dorsal hippocampus or parietal cortex differentially affect spatial information processing.

The present experiments used 2 versions of a modified Hebb-Williams maze to test the role of the dorsal hippocampus (dHip) and parietal cortex (PC) in processing allocentric and egocentric space during acquisition and retention. Bilateral lesions were made to either the dHip or PC before maze testing (acquisition) or after maze testing (retention). The results indicate that lesions of the dHip impair allocentric maze acquisition, whereas lesions of the PC impair egocentric maze acquisition. During retention, lesions of the PC produced a significant impairment on both maze versions, whereas lesions of the dHip produced short-lived, transient impairments on both maze versions. These results suggest that during acquisition, the hippocampus and PC process spatial information in parallel; however, long-term retention of spatial information requires the PC with the dHIP as necessary for retrieval and/or access but not necessarily storage. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Phencyclidine injections into the dorsal hippocampus disrupt long- but not short-term memory within a spatial learning task

Since the hippocampus is likely to be a major site of phencyclidine (PCP) action, the effects of various doses of PCP (1.8, 18 or 36 nM) as well as 3.6 nM MK-801 or saline injected directly into the dentate gyrus of the hippocampus was tested for acquisition of a spatial navigation task (dry land version of a water maze) using a paradigm that assesses short term memory based on learning within a day and long term memory based on learning between days. Results indicated that relative to saline or 1.8 nM PCP injected rats, rats with 18 or 36 nM PCP or 3.6 nM MK-801 injections were impaired in acquisition of the task as measured by increased distances traveled to find the food location between days but not within days. In additional experiments 36 nM PCP or 3.6 nM MK-801 did not produce any deficits in the acquisition of an object discrimination task. It is suggested that PCP through its blocking action of the NMDA receptor in the dentate gyrus or CA1 region of the dorsal hippocampus mediates the consolidation of new spatial location information.     

The cerebellum in the spatial problem solving: a co-star or a guest star?

The experimental findings reviewed here indicate that the cerebellum has to be added to the regions known to be involved in the spatial learning. Cerebellar function is specifically linked to 'how to find an object' rather than 'where the object is in the space'. In the Morris water maze (MWM) hemicerebellectomized (HCbed) rats displayed a severe impairment in coping with spatial information, displaying only peripheral circling. And yet, when the MWM cue phase was prolonged, HCbed rats succeeded in acquiring some abilities to learn platform position, even in a pure place paradigm, such as finding a hidden platform with the starting points sequentially changed. Conversely, whether the searching strategy was acquired preoperatively, no exploration deficit appeared. Thus, cerebellar lesions appear to affect the procedural components of spatial function, sparing the declarative ones. When intact animals were non-spatially pre-trained and then HCbed, they exhibited an expanded scanning strategy, underlining the cerebellar involvement in procedural component acquisition. By testing HCbed rats in an active avoidance task, first without and then with a request for right/left discrimination, lesioned rats displayed severe deficits. Thus, besides a marked impairment in facing procedural components of spatial processing, cerebellar lesion provokes deficits also in right/left discrimination task. In conclusion, it is possible to propose the cerebellum as one part of a large system that includes frontal, posterior parietal, inferior temporal cortices, hippocampus and basal ganglia. These structures form an allocentric spatial system and an egocentric control system, that interlock to process the information involved in representing an object in the space.     

Characterization of perforant path lesions in rodent models of memory and attention

Early stage Alzheimer's disease (AD) pathology is associated with neurodegeneration of systems within the temporal cortex, e.g. the entorhinal cortex, perforant pathway and hippocampus. The perforant pathway provides the major neuronal input to the hippocampus from the entorhinal cortex and thus relays multimodal sensory information derived from cortical zones into the hippocampus. The earliest symptoms of AD include cognitive impairments, e.g. deficits in short-term memory and attention. Consequently, we have investigated the effect of bilateral knife cut lesions to the perforant path on cognition in rats using models measuring primarily short-term memory (operant delayed match to position task), attention (serial five-choice reaction time task) and spatial learning (Morris water maze). Rats receiving bilateral perforant path lesions showed normal neurological function and a mild hyperactivity. The lesion produced little effect on attention assessed using the five-choice task. In contrast, animals with equivalent lesions showed a robust delay-dependent deficit in the delayed match to position task. Spatial learning in the water maze task was also severely impaired. The delay-dependent deficit in the match to position task was not reversed by tacrine (3 mg/kg) pretreatment. The present data support a selective impairment of cognitive function following perforant path lesions that was confined to mnemonic rather than attentional processing. These findings complement primate and human studies identifying a critical role of the perforant pathway and associated temporal lobe structures in declarative memory. Degeneration of the perforant pathway is likely to contribute to the mnemonic deficits characteristic of early AD. The failure of tacrine to ameliorate these deficits may be relevant to an emerging clinical literature suggesting that cholinomimetic therapies improve attentional rather than mnemonic function in AD.     

Movement-associated neural excitation as a factor in spatial representational memory in rats.

The hypothesis that rats require an attentionlike function arising from integration of exteroceptive and movement-related excitation during the information phase of representational memory–dependent discriminations is proposed. Experiments 1A and 1B (both behavioral) demonstrated the crucial importance of movement-related excitation (angle of turn at T-maze choice point). Experiment 2 showed that, contrary to plausible expectations, ablation of putative posterior parietal association cortex only mildly affected memory. This finding agrees with the notion of a nonspecific mass action–equipotential effect of ablations in nondifferentiated cortex on memory rather than the specific effects resulting from dorsolateral prefrontal ablations in primates. Instead, it is proposed from previous data (e.g., K. M. Heilman et al, 1987) that the hippocampus integrates movement-related and exteroceptive excitations necessary for representational memory, which is largely restricted to spatial attributes in rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tuning out irrelevancy? Comments on Solomon's temporal mapping view of the hippocampus.

In his analysis of the present author's series of studies on the role of the hippocampus in spatial information processing (A. H. Black, L. Nadel, and J. O'Keefe; 1974, 1975, 1976, 1979), P. R. Solomon (see record 1980-04864-001) proposed an extension to the cognitive map theory of hippocampal function. He cites evidence drawn mainly from the literature on the classical conditioning of the rabbit's nictitating membrane response, which he claims can not be satisfactorily explained within the framework of the present theory. The present article shows that the deficits following hippocampal lesions can be predicted from understanding the role of place learning in each paradigm and shows that electrophysiological data are open to different interpretation. It is concluded that the data cited by Solomon do not require any modification of the theory. (2 p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of CA3 and CA1 in the acquisition of an object-trace-place paired-associate task.

The hippocampus mediates associative learning involving spatial and temporal information. Specifically, paired associations in which a trace interval separates the elements appear to be associated within CA1. In contrast, CA3 appears to be involved in associations containing spatial elements. This suggests that CA3, but not CA1, is involved as long as the spatial association does not contain temporal elements; conversely, CA1 is involved when a temporal element is included, regardless of whether there are spatial elements present. In the present study, rats were run on an object-trace-place paired-associate learning paradigm. Rats with CA3 as well as rats with CA1 lesions showed deficits in the acquisition of this task. These results suggest that CA1 is involved in making arbitrary associations involving a temporal (trace) element, whereas CA3 is involved in making associations that involve spatial elements; furthermore, CA1 and CA3 interact in the presence of both spatial and temporal information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chronic Oral Estrogen Affects Memory and Neurochemistry in Middle-Aged Female Mice.

This study tested whether chronic oral estrogen could improve memory and alter neural plasticity in the hippocampus and neocortex of middle-aged female mice. Ovariectomized C57BL/6 mice were administered 1,000, 1,500, or 2,500 nM 17β-estradiol in drinking water for 5 weeks prior to and during spatial and object memory testing. Synaptophysin, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) levels were then measured in hippocampus and neocortex. The medium dose impaired spatial reference memory in the radial-arm maze, whereas all doses improved object recognition. The high dose increased hippocampal synaptophysin and NGF levels, whereas the medium dose decreased these neocortical levels. The high dose decreased neocortical BDNF levels. These data suggest that chronic oral estrogen selectively affects memory and neural function in middle-aged female mice. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Role of Hippocampal Subregions in Detecting Spatial Novelty.

Previous literature suggests that the hippocampus subserves processes associated with the encoding of novel information. To investigate the role of different subregions of the hippocampus, the authors made neurotoxic lesions in different subregions of the dorsal hippocampus (i.e., CA1, dentate gyrus [DG], or CA3) of rats, followed by tests using a spontaneous object exploration paradigm. All lesion groups explored normally an object newly introduced in a familiar location. However, when some of the familiar objects were moved to novel locations, both DG and CA3 lesion groups were severely impaired in reexploring the displaced objects, whereas the CA1 lesion group was only mildly impaired in reexploration. The results suggest that the DG-CA3 network is essential in detecting novelty for spatial, but not for individual object, information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)