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)     

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.     

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)     

Pharmacological evidence of the role of dorsal striatum in spatial memory consolidation in mice.

This study investigated the role of dorsal striatum in spatial memory in mice. The mice were tested for their ability to detect a spatial displacement 24 hrs after training. In order to manipulate the dorsal striatum, focal administrations of the N-methyl-D-aspartate (NMDA) antagonist D-2-amino-5 phosphonopentanoic acid (AP-5) were performed immediately after training. AP-5 impaired the mice's ability to detect the spatial change only if their initial position was constant during training and testing. These findings demonstrate that NMDA receptor blockade within the dorsal striatum impairs spatial memory consolidation in a task in which no explicit reward or procedural learning is involved. The results are discussed with reference to a possible selective involvement of this structure in processing spatial information acquired through an egocentric, but not an allocentric, frame of reference. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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 omega-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 omega-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.     

Learning upregulates brain-derived neurotrophic factor messenger ribonucleic acid: a mechanism to facilitate encoding and circuit maintenance?

Brain-derived neurotrophic factor (BDNF) promotes neuron survival, enhances sprouting, protects neurons against insult, and may be involved in several aspects of learning and memory. In this study, rats trained to locate a submerged platform in a water maze had elevated levels of BDNF messenger ribonucleic acid (mRNA) in the hippocampus (p < .05), a structure associated with spatial memory. BDNF mRNA expression increased after 3 and 6 days but not after 1 day of training in the water maze. A yoked control group that swam without the platform present, to control for physical activity, showed a trend for elevated BDNF mRNA at an intermediate level between the learning and sedentary groups. Other cortical and subcortical areas did not show a significant increase in BDNF mRNA after learning or activity (p > .05). These findings suggest that learning can impact BDNF mRNA expression localized to the brain areas involved in the processing of spatial information. Furthermore, behaviors such as physical activity and learning may help maintain and protect neurons at risk in aging and neurodegenerative disease via increased BDNF expression.     

Different hippocampal activity profiles for PKA and PKC in spatial discrimination learning.

Protein kinases are considered essential for the processing and storage of information in the brain. However, the dynamics of protein kinase activation in the hippocampus during spatial learning are poorly understood. In this study, rats were trained to learn a holeboard spatial discrimination task and the activity profiles for cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) and Ca2+/ phospholipid-dependent protein kinase C (PKC) in the hippocampus were examined. Hippocampal PKA activity increased rapidly on Day 1 of spatial learning and remained moderately high at later stages of acquisition. In contrast, PKC activity increased in particulate fractions compared with cytosolic fractions after habituation training and was maximal at Day 3 of spatial acquisition. The results establish a temporal dissociation between PKA and PKC during acquisition of spatial discrimination learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rats with hippocampal lesions can learn a place response, but how long can they retain it?

Previous research has shown that electrolytic hippocampal lesions do not affect the acquisition of a place response if a special training procedure is used. However, 24 days later, the hippocampal rats manifest a profound deficit in the retention of the spatial information (J. A. J. Ramos, 2000). The goal of the present study was, therefore, to investigate how long the hippocampal rats can retain a place response. Results showed that, 3 days after the end of the training, lesioned rats remembered as well as the control rats, but this was no longer true 6 or 12 days after the training. This retention deficit was not observed when the spatial information was acquired by means of a guidance strategy. These results suggest that, when a special training procedure is used, the hippocampus is not necessary for the learning of a place task but is required for the formation of long-term spatial memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neural Correlates of Individual Differences in Spatial Learning Strategies.

Behavioral studies have shown that spatial skills, such as mental rotation, are correlated with preferences for certain types of spatial information. To be more specific, better mental rotation is associated with a preference for survey (maplike) spatial information relative to route (landmark or wayfinding) information. Functional MRI was used to investigate how individual differences in spatial skills (mental rotation) interact with encoding information from these 2 spatial perspectives. Despite similarities in performance across individuals for route and survey learning, differences between route and survey encoding activation increased with increased mental rotation ability in anterior cingulate, middle frontal gyrus, and postcentral gyrus. This correlation appeared to be due to decreasing activation during survey encoding and not activation changes during route learning. The results suggest that mental rotation skill contributes to survey or map learning but that alternative strategies can be used under the circumstances of this study to achieve equal performance. (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.     

Short-term memory for duration and distance in humans: Role of the hippocampus.

Control participants and hypoxic participants with bilateral hippocampal damage were tested for short-term memory (STM) for presentation duration of a single object, STM for a single object, STM for spatial distance information, and time estimation. Delays of 1, 4, 8, 12, or 16 s were used for all the STM and time estimation tests. Results indicated that relative to controls, hypoxic participants were significantly impaired for STM for duration and distance information at the long but not short delays. Similarly, time estimation was accurate only to 8 s for hypoxic participants, but STM for a single object was only mildly affected. Results suggest that the hippocampus may be required for the processing of spatial and temporal STM information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

Effects of Fimbria-Fornix, Hippocampus, and Amygdala Lesions on Discrimination Between Proximal Locations.

The conditioned cue preference (CCP) task was used to study the information required to discriminate between spatial locations defined by adjacent arms of an 8-arm radial maze. Normal rats learned the discrimination after 3 unreinforced preexposure (PE) sessions and 4 food paired-unpaired training trials. Fimbria-fornix lesions made before, but not after, PE, and hippocampus lesions made at either time, blocked the discrimination, suggesting that the 2 structures processed different information. Lateral amygdala lesions made before PE facilitated the discrimination. This amygdala-mediated interference with the discrimination was the result of a conditioned approach response that did not discriminate between the 2 arm locations. A hippocampus/fimbria-fornix system and an amygdala system process different information about the same learning situation simultaneously and in parallel. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Episodic long-term memory in the rat: Effects of hippocampal stimulation.

Seven male Long-Evans rats with electrodes implanted in the dorsal hippocampus were trained to perform a delayed spatial matching-to-sample task on a radial arm maze. Subseizure-level electrical stimulation of the dorsal hippocampus applied during the study phase disrupted retention of a specific arm when tested at a 20-min delay but had no effects at 1- and 12-min delays. Subseizure-level stimulation of the hippocampus immediately after the study phase resulted in normal retention. In contrast, seizure-level stimulation of the hippocampus applied either during or immediately after the study phase disrupted retention at 1-, 12-, and 20-min delays. Data support the interpretation that the hippocampus is involved in the encoding of critical information (spatiotemporal attributes) in long-term working memory, but not in short-term memory. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preserved negative patterning and impaired spatial learning in pigeons (Columba livia) with lesions of the hippocampus.

Pigeons (Columba livia) with bilateral electrolytic lesions of the hippocampus and area parahippocampalis were compared with control pigeons on 2 tasks: negative patterning and delayed spatial alternation. Negative patterning demands configural stimulus representations for its successful solution. The only effect of hippocampal lesions on this task was an increased response rift to the rewarded stimuli. On the delayed spatial alternation task, hippocampal birds showed deficits relative to controls. Differences in the results of prior studies on negative patterning appear to be due to different response requirements to the nonreinforced stimuli. These results are consistent with prior work with rats and suggest that the avian hippocampus is essential for spatial memory and response inhibition but is not involved in configural learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporal versus spatial information processing theories of hippocampal function.

Several articles by A. H. Black, L. Nadel, J. O'Keefe, and their co-workers (1974, 1975, 1976, 1979) propose that the primary function of the hippocampus is to process spatial information. Although the spatial information processing view of hippocampal function accounts for much of the available data, it cannot account for the data from the classically conditioned rabbit nictitating membrane response preparation. The present article reviews these data and suggests that the hippocampus is involved in the processing of temporal as well as spatial information. (46 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Long-Term Memory for Spatial Locations in a Food-Storing Bird (Poecile atricapilla) Requires Activation of NMDA Receptors in the Hippocampal Formation During Learning.

Food-storing birds use a form of long-term memory to recover their hidden food caches that depends on the hippocampal formation (HF). The authors assessed whether food-storing birds' long-term memory for spatial locations requires N-methyl-D-aspartate receptor (NMDA-R)-dependent synaptic plasticity. Black-capped chickadees (Poecile atricapilla) were given bilateral infusions of the NMDA-R antagonist AP5 into the hippocampus, and their memory on a spatial reference memory task was assessed. NMDA-R inactivation during learning prevented formation of long-term spatial memories but did not affect short-term memory and retrieval processes. NMDA-R inactivation immediately following learning did not disrupt long-term memory formation. NMDA-R inactivation disrupted the learning of multiple serially encoded reward locations when a 180-min delay separated successive learning episodes, suggesting that NMDA-R activity has a role in the incorporation of new information into existing long-term memory, as well as in forming unitary long-term memories. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A double dissociation between the rat hippocampus and medial caudoputamen in processing two forms of knowledge.

Rats with hippocampus, medial caudoputamen (CPU), lateral CPU, or control lesions were trained on declarative and procedural knowledge variants of a novel rodent sequential learning task. Medial CPU lesions impaired rats' ability to learn the procedure of running through a sequence of open maze arms but did not disrupt their capacity to explicitly generate (i.e., "declare") maze arm sequences. Hippocampus lesions produced the opposite set of results. Rats with lateral CPU lesions were not impaired on either version of the task. Transfer tests indicated that control rats predominantly used egocentric cues to solve the procedural task and allocentric spatial cues to solve the declarative task. These findings suggest a double dissociation between the medial CPU and hippocampus in processing egocentric-procedural and allocentric- declarative sequential information, respectively. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Implicit, long-term spatial contextual memory.

Learning and memory of novel spatial configurations aids behaviors such as visual search through an implicit process called contextual cuing (M. M. Chun & Y. Jiang, 1998). The present study provides rigorous tests of the implicit nature of contextual cuing. Experiment 1 used a recognition test that closely matched the learning task, confirming that memory traces of predictive spatial context were not accessible to conscious retrieval. Experiment 2 gave explicit instructions to encode visual context during learning, but learning was not improved and conscious memory remained undetectable. Experiment 3 illustrates that memory traces for spatial context may persist for at least 1 week, suggesting a long-term component of contextual cuing. These experiments indicate that the learning and memory of spatial context in the contextual cuing task are indeed implicit. The results have implications for understanding the neural substrate of spatial contextual learning, which may depend on an intact medial temporal lobe system that includes the hippocampus (M. M. Chun & E. A. Phelps, 1999). (PsycINFO Database Record (c) 2010 APA, all rights reserved)