Localization of Function Within the Dorsal Hippocampus: The Role of the CA3 Subregion in Paired-Associate Learning.

Computational models and electrophysiological data suggest that the CA3 subregion of the hippocampus supports the formation of arbitrary associations; however, no behavioral studies have been conducted to test this hypothesis. Rats with neurotoxin-induced lesions of dorsal dentate gyrus (DG), CA3, or CA1 were tested on object-place and odor-place paired-associate tasks to test whether the mechanism that supports paired-associate learning is localized to the CA3 subregion of the dorsal hippocampus or whether all hippocampal subregions contribute to paired-associate learning. The data indicate that rats with DG or CA1 lesions learned the tasks as well as controls; however, CA3-lesioned rats were impaired in learning the tasks. Thus, the CA3 subregion of the dorsal hippocampus contains a mechanism to support paired-associate learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociating the roles of dorsal and ventral CA1 for the temporal processing of spatial locations, visual objects, and odors.

The differential contributions of the dorsal and ventral hippocampus for learning and memory have long been of interest. The present experiments were designed to evaluate the contributions of dorsal CA1 and ventral CA1 for temporal processing. Animals were run on three temporal ordering paradigms: one with visual objects, one with olfactory stimuli, and one with spatial locations. Animals with lesions to dorsal CA1 showed deficits for the temporal ordering of visual objects relative to control animals, and deficits for the temporal ordering of spatial locations relative to control and ventral CA1 lesioned animals. Animals with lesions to ventral CA1 showed deficits for the temporal ordering of olfactory information relative to control and dorsal CA1 lesioned animals, and a mild deficit for the temporal ordering of visual objects relative to control animals, but not as severe as those shown by the dorsal CA1 lesioned animals. These data suggest that dorsal CA1 and ventral CA1 contribute to temporal ordering processes, and that dorsal CA1 and ventral CA1 are dissociable for temporal ordering based upon the nature of the information that is processed. (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)     

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)     

The CA3 subregion of the hippocampus is critical for episodic memory processing by means of relational encoding in rats.

This experiment tested the theory that the CA3 subregion of the hippocampus mediates episodic learning of arbitrary associations. The authors developed 2 tasks based on the episodic flavor-place paired-associate task described by M. Day, R. Langston, and R. G. Morris (2003): an object-cued spatial location recall task and a spatial location-cued object recall task. After rats were trained to a criterion of 80% correct on 1 of the 2 tasks, they received either a dorsal CA3 lesion or a vehicle control lesion. Control animals continued performing well on both tasks. Rats with lesions to dorsal CA3 were impaired on both tasks and performed at chance but were able to perform a nonepisodic version of the task as a control. These data suggest that CA3 mediates episodic learning of arbitrary associations as tested in the 1-trial object-cued spatial location recall and spatial location-cued object recall tasks. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Role of CA1 in the Acquisition of an Object-Trace-Odor Paired Associate Task.

This experiment was designed to determine whether adding a temporal component to an object-odor association task would recruit the hippocampus. The rats were given CA1, CA3, or control lesions prior to learning the object-trace-odor task. Rats were presented with an object for 10 s, after which the object was removed, followed by a 10-s trace period, followed by the presentation of an odor 50 cm away. If the odor and the object were paired, rats were to dig in the odor cup for a reward. If unpaired, rats were to refrain from digging. Rats that had CA1 lesions were unable to make the association, whereas rats that had CA3 lesions performed as well as controls. These results support the idea that the hippocampus is involved in forming arbitrary associations that do not necessarily involve space as long as they involve a temporal component. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Olfactory learning and memory impairments following lesions to the hippocampus and perirhinal-entorhinal cortex.

The role of the hippocampus and perirhinal-entorhinal cortex was examined in an olfactory discrimination paradigm. Small neurotoxic lesions of the hippocampus (21% tissue damage) yielded relatively unimpaired olfactory retention across brief (30 s), intermediate (approximately 5 min), and 24-hr delays, whereas impairments were noted at 5-day retention intervals. Larger hippocampal lesions (63% tissue damage) spared memory at intermediate delays, with no impact at 8-day retention intervals. Aspiration lesions directed at the perirhinal-entorhinal cortex produced a variable performance pattern, with impairments noted at intermediate, 24-hr, and 5-day delays. Results suggest the hippocampus is not specifically involved in retaining olfactory information, with additional consideration given to the relationship between lesion size and memory impairment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociation of the effects of bilateral lesions of the dorsal hippocampus and parietal cortex on path integration in the rat.

Rodents are able to rely on self-motion (idiothetic) cues and navigate toward a reference place by path integration. The authors tested the effects of dorsal hippocampal and parietal lesions in a homing task to dissociate the respective roles of the hippocampus and the parietal cortex in path integration. Hippocampal rats exhibited a strong deficit in learning the basic task. Parietal rats displayed a performance impairment as a function of the complexity of their outward paths when the food was placed at varying locations. These results suggest that the parietal cortex plays a specific role in path integration and in the processing of idiothetic information, whereas the hippocampus is involved in the calibration of space used by the path integration system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of the hippocampus in memory for the temporal order of a sequence of odors.

Memory for the temporal order of a sequence of odors was assessed in rats. A sequence of 5 odors mixed in sand was presented in digging cups, 1 at a time, to each rat in a sequence that varied on each trial. A reward was buried in each cup. After the 5th odor, 2 of the previous 5 odors were presented simultaneously; to receive a reward, the rat had to choose the odor that occurred earliest in the sequence. Temporal separations of 1, 2, or 3 represented the number of odors that occurred between the 2 odors in the sequence. Once a preoperative criterion was reached, each rat received a hippocampal (HIP) or cortical control lesion and was retested on the task. On postoperative trials, the HIP group was impaired relative to controls. However, the HEP group could discriminate between the odors. The data suggest that the hippocampus is involved in separating sensory events in time so that 1 event can be remembered separately from another event. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dorsal hippocampus involvement in trace fear conditioning with long, but not short, trace intervals in mice.

Placing a "trace" interval between a warning signal and an aversive shock makes consolidation of the memory for trace conditioning hippocampus dependent. To determine the trace at which memory consolidation requires the hippocampus, mice were trained with 0-s, 1-s, 3-s, or 20-s trace intervals and tested for freezing to context and tone. Posttraining dorsal hippocampus (DH) lesions decreased context conditioning regardless of trace interval. However, DH lesions attenuated only the 20-s trace tone freezing. Like eyeblink conditioning, the DH is necessary for trace fear conditioning only at long trace intervals, but the time scale for the effective interval in fear conditioning is about 40 times longer. Manipulations that alter trace fear conditioning with short trace intervals probably do not reflect altered DH function. Given this difference in time scale along with the use of posttraining DH lesions, hippocampus dependency of trace conditioning is not related to a bridging function or response timing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampus and Pavlovian Fear Conditioning in Rats: Muscimol Infusions Into the Ventral, but Not Dorsal, Hippocampus Impair the Acquisition of Conditional Freezing to an Auditory Conditional Stimulus.

The authors compared the effects of pharmacological inactivation of the dorsal hippocampus (DH) or ventral hippocampus (VH) on Pavlovian fear conditioning in rats. Freezing behavior served as the measure of fear. Pretraining infusions of muscimol, a GABAA receptor agonist, into the VH disrupted auditory, but not contextual, fear conditioning; DH infusions did not affect fear conditioning. Pretesting inactivation of the VH or DH did not affect the expression of conditional freezing. Pretraining electrolytic lesions of the VH reproduced the effects of muscimol infusions, whereas posttraining VH lesions disrupted both auditory and contextual freezing. Hence, neurons in the VH are importantly involved in the acquisition of auditory fear conditioning and the expression of auditory and contextual fear under some conditions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Excitotoxic lesions of the hippocampus leave sensory preconditioning intact: Implications for models of hippocampal functioning.

Learning about contextual cues is markedly disrupted in rats with hippocampal lesions. One analysis of this disruption is that it reflects a general failure to form associations between the elements of complex events. A straightforward prediction of this analysis is that sensory preconditioning will be disrupted by hippocampal lesions. This prediction was assessed by presenting rats with flavored solutions composed of 2 elements (A and X) before X was paired with an injection of the emetic, lithium chloride. A subsequent test revealed that rats were less willing to consume Solution A than they were to consume a control solution, B. This was true of rats with sham lesions and those with excitotoxic lesions of hippocampus. These findings fail to support the proposition that the hippocampus-dependent deficit in contextual conditioning is due to a general disruption to the process of associating the elements of complex events. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociable onset of cognitive and motivational dysfunctions following neonatal lesions of the ventral hippocampus in rats.

This research examined cognitive and motivational processes at different developmental stages in rats with neonatal ventral hippocampus (VH) lesions, an approach used to model schizophrenia. In Experiment 1, performance in a T-maze alternation task was assessed on postnatal days (PNDs) 22 and 23. VH-lesioned rats displayed a severe deficit relative to controls. In Experiment 2, behaviorally naive rats were tested for spontaneous alternation at PND 29. Alternation was intact in VH-lesioned rats only when successive alternations were separated by >5 s. In Experiment 3, motivation was tested in a cost-benefit T-maze task and in a saccharine-water preference test. Between PNDs 22-37, behaviorally naive rats with neonatal VH lesions displayed weaker saccharine preference than controls, but the 2 groups did not differ on the cost-benefit task. At adulthood, between PNDs 56-72, the difference on saccharine preference persisted and an impairment on the cost-benefit task emerged. Overall, these results suggest that working memory deficits observed at the weaning stage were not secondary to spontaneous alternation or motivation dysfunctions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Role of Hippocampal Regions CA3 and CA1 in Matching Entorhinal Input With Retrieval of Associations Between Objects and Context: Theoretical Comment on Lee et al. (2005).

Models of hippocampal function have proposed different functions for hippocampal regions CA3 and CA1, commonly proposing that CA1 performs a match-mismatch comparison of memory retrieval with sensory input. The study by I. Lee, M. R. Hunsaker, and R. P. Kesner (2005) tested these models using selective lesions of hippocampal subregions (see record 2005-01705-014). Their data suggest that CA3 and the dentate gyrus play an important role in the process of detecting the mismatch when a familiar object is placed in a new spatial location. Lesions of the dentate gyrus and CA3 strongly reduce the enhanced exploration associated with displaced objects, beyond the reduction caused by CA1 lesions. This supports the importance of convergent input to CA3 as well as CA1. Along with recent electrophysiological data, this provides a framework for more specifically modeling the role of CA3 and CA1 in matching sensory input with context-dependent retrieval for memory-guided behavior in different tasks. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A behavioral analysis of the role of CA3 and CA1 subcortical efferents during classical fear conditioning.

It has been proposed that the hippocampus and subcortical structures interact during the processing of fear and anxiety-related information. It has been demonstrated that the subcortical efferents from CA3 and CA1 can be selectively disrupted without concomitant disruption to the afferents. The present experiment was designed to evaluate the role of CA3 efferents via the fimbria and the CA1 efferents via the dorsal fornix for encoding and consolidation/retrieval of classical fear conditioning. The present data suggest that the subcortical projections from CA3 and CA1 are differentially involved in the processing of classical fear conditioning, with CA3 subcortical efferents supporting acquisition of both cued and contextual fear but only supporting retention of contextual fear and CA1 subcortical efferents supporting the encoding and retrieval of both cued and contextual fear. These data further suggest that all hippocampal efferents are not homogeneous, and that the hippocampus and subcortex interact to process conditioned fear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Entorhinal cortex lesions disrupt the transition between the use of intra- and extramaze cues for navigation in the water maze.

[Correction Notice: An erratum for this article was reported in Vol 117(5) of Behavioral Neuroscience (see record 2007-16848-001). The definitions "Present = intramaze landmark present during Stage 2" and "Absent = intramaze landmark absent during Stage 2" appear incorrectly in the caption to Figure 3. These terms and definitions should appear in the caption to Figure 4.] This study with rats examined the effects of excitotoxic lesions to the entorhinal cortex (EC) and hippocampus (HPC) on using extramaze and intramaze cues to navigate to a hidden platform in a water maze. HPC lesions resulted in a disruption to the use of extramaze cues, but not intramaze cues, whereas EC lesions had no effect on the use of these cues when they were encountered for the fast time. However, prior navigation training in which 1 type of cue was relevant disrupted navigation with the other type in rats with EC lesions. Results show that the EC contributes to the processing of spatial information, but that this contribution is most apparent when there is a conflict between 2 sources of navigational cues in the water maze. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of dorsal hippocampus and basolateral amygdala NMDA receptors in the acquisition and retrieval of context and contextual fear memories.

The authors used 3-phase context preexposure facilitation methodology to study the contribution of N-methyl-D-aspartate (NMDA) receptors in dorsal hippocampus (DH) and the basal lateral region of the amygdala (BLA) to (a) acquisition of the context memory, (b) retrieval of the context memory, (c) acquisition of context-shock association, and (d) retrieval of the context-shock association. The NMDA receptor antagonist D-2-amino-5 phosphonopentanoic acid (D-AP5) was injected into either the DH or BLA prior to (a) the context preexposure phase, (b) the immediate shock phase, or (c) the test for contextual fear. Antagonizing NMDA receptors in the DH impaired the acquisition of the context memory but did not affect its retrieval or retrieval of the fear memory. Antagonizing NMDA receptors with D-AP5 in the BLA impaired acquisition of the context-shock association but had no effect on the expression of fear. However, both DL-AP5 and L-AP5 reduced the expression of fear when they were injected into the amygdala prior to testing for contextual fear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dorsal hippocampus inhibition disrupts acquisition and expression, but not consolidation, of cocaine conditioned place preference.

Cocaine abusers may experience drug craving upon exposure to environmental contexts where cocaine was experienced. The dorsal hippocampus (DHC) is important for contextual conditioning, therefore the authors examined the specific role of the DHC in cocaine conditioned place preference (CPP). Muscimol was used to temporarily inhibit the DHC and was infused before conditioning sessions or tests for CPP to investigate acquisition and expression of cocaine CPP, respectively. To investigate consolidation, rats received intra-DHC muscimol either immediately or 6 hr after conditioning sessions. Inhibition of DHC, but not the overlying cortex, disrupted acquisition and expression of cocaine CPP. It is interesting to note that there was no effect of postconditioning DHC inhibition. The findings suggest that the DHC is important for both acquisition and recall, but not consolidation, of context-cocaine associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pattern memory involves both elemental and configural processes: Evidence from the effects of hippocampal lesions.

The formation of an integrated memory for a pattern of stimulation could be based on the elements of that pattern becoming directly linked to one another, or by each of the elements becoming linked to a shared separate configural representation. These 2 accounts have proven difficult to discriminate between. Here, rats received exposure to four patterns of stimulation, each consisting of an auditory stimulus, a visual context, and a time of day; and we examined whether pre-training lesions to the hippocampus influenced memory for the patterns. These lesions abolished pattern memory that required configural processes (Experiments 1A and 1B) but had no effect on pattern memory that could be supported by elemental processes (Experiment 2). This dissociation provides support for the views that elemental and configural processes ordinarily support pattern memory and that rats with lesions to the hippocampus are left reliant on elemental processes. (PsycINFO Database Record (c) 2011 APA, all rights reserved)