Dorsal hippocampus, CA3, and CA1 lesions disrupt temporal sequence completion.

An experiment was designed to evaluate effects of dorsal hippocampus, dorsal CA3a,b, dorsal CA1, and control lesions on performance of a temporal sequence task. Rats were trained on a sequential learning task involving six spatial locations on a radial 8-arm maze. After initial training followed by surgery, it was found that all lesioned animals were able to remember the sequence. To test temporal sequence completion, rats were started at different positions in the sequence and expected to complete the remainder of the sequence. The results indicate that control rats had no difficulty completing the sequence, regardless of starting point. In contrast, rats with dorsal hippocampus and dorsal CA3a,b lesions made errors by always returning to the first position in the sequence, regardless of which start position was used, whereas rats with dorsal CA1 lesions made random errors in the process of completing the sequence and did not appear to remember the serial order of the spatial sequence. This suggests that the dorsal hippocampus, and specifically the dorsal CA3 in conjunction with CA1, may be involved in temporal pattern completion processes. (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 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)     

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)     

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)     

Transfer of Spatial Behavior Between Different Environments: Implications for Theories of Spatial Learning and for the Role of the Hippocampus in Spatial Learning.

In 3 experiments, rats were required to find a submerged platform located in 1 corner of an arena that had 2 long and 2 short sides; they were then trained to find the platform in a new arena that also had 2 long and 2 short sides but a different overall shape. The platform in the new arena was easier to find if it was in a corner that was geometrically equivalent, rather than the mirror image, of the corner where it had previously been located. The final experiment revealed that hippocampal lesions impaired rats' ability to find the platform in these arenas. The results suggest that rats did not use the overall shape of the arena to locate the platform but relied on more local cues and that the hippocampus plays a role in navigation based on these cues. (PsycINFO Database Record (c) 2011 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)     

Arbitrary associations in animals: What can paired associate recall in rats tell us about the neural basis of episodic memory? Theoretical comment on Kesner, Hunsaker, & Warthen (2008).

Detailed memories for unique episodes from an individual's past can be triggered, often effortlessly, when that individual is exposed to a stimulus that was present during the original event. The aim of Kesner et al. (see record 2008-17011-003) is to understand the neural basis of memory encoding that supports this cued recall of episodic memories. Kesner and colleagues make novel use of an object-place paired-associate task for rats to provide evidence for a critical role of dorsal CA3 in certain aspects of episodic memory encoding. Using one-trial cued recall versions of the task they show that when rats are cued with an object stimulus, they can be trained to revisit the location in which the object appeared previously. Conversely, when rats are cued with a location, they can learn to choose the object with which it was associated. Rats with dorsal CA3 lesions are severely impaired at these tasks. These data are consistent with the theory that the autoassociative network in CA3 supports the rapid formation of novel associations and may allow pattern completion--the phenomenom whereby a subset of the cues present at an encoding event triggers recall of the whole event. Although flexible recall of arbitrary associations is not fully demonstrated, the study contributes 2 novel behavioral tasks to the previously limited repertoire for studying paired associate recall in rats. It also builds on previous data to specify the role of the hippocampal CA3 subregion in cued recall--a critical aspect of episodic memory. (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)     

Instrumental Learning Within the Rat Spinal Cord: Localization of the Essential Neural Circuit.

Following spinal transection of the upper thoracic spinal cord, male Sprague-Dawley rats given legshock whenever a hindlimb is extended learn to maintain the leg in a flexed position. The region of the cord that mediates this instrumental learning was isolated using neuroanatomical tracing, localized infusion of lidocaine, and surgical transections. DiI and Fluoro-Gold microinjection at the site of shock application labeled motor neuron bodies of lamina IX in the lower lumbar region. Local application of the Na++ channel blocker lidocaine disrupted learning when it was applied over a region extending from the lower lumbar (L3) to upper sacral (S2) cord. The drug had no effect rostral or caudal to this region. Surgical transections as low as L4 had no effect on learning. Learning also survived a dual transection at L4 and S3, but not L4 and S2. The results suggest that the essential neural circuit lies between L4 and S3. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Blockade of Central Cholinergic Receptors Impairs New Learning and Increases Proactive Interference in a Word Paired-Associate Memory Task.

Experimental data and computational models suggest that blockade of muscarinic cholinergic receptors impairs paired-associate learning and increases proactive interference (E. DeRosa & M. E. Hasselmo, 2000; M. E. Hasselmo & J. M. Bower, 1993). The results presented here provide evidence in humans supporting these hypotheses. Young healthy subjects first learned baseline word pairs (A-B) and, after a delay, learned additional overlapping (A-C) and nonoverlapping (D-E) word pairs. As predicted, when compared with subjects who received the active placebo glycopyrrolate (4 μg/kg) and subjects who were not injected, those who received scopolamine (8 μg/kg) showed (a) overall impairment in new word paired-associate learning, but no impairment in cued recall of previously learned associates; and (b) greater impairment in learning overlapping (A-C) compared with nonoverlapping (D-E) paired associates. (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)     

Lesions of the Dorsal Hippocampus Block Trace Fear Conditioned Potentiation of Startle.

Several studies show that the hippocampus is critical for the memories mediating trace and contextual fear conditioning. This study investigates whether N-methyl-D-aspartate-induced lesions of the dorsal hippocampus made prior to training affect context fear conditioning and trace fear conditioning measured with the fear-potentiated startle. Pretraining excitotoxic lesions of the dorsal hippocampus blocked acquisition of trace fear conditioning to a tone stimulus but did not affect context fear conditioning. These data indicate that without a dorsal hippocampus rats are unable to acquire trace conditioning but can acquire contextual fear when fear is measured by potentiation of the startle response. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Effects of Hippocampal Lesions on Response, Direction, and Place Learning in Rats.

Rats with hippocampal or sham lesions were trained to find food on a T maze located at 2 positions. Response rats were required to make a right or left turn. Direction rats were required to go in a consistent direction (east or west). Place rats were required to go to a consistent location, relative to room cues. One place group had distinguishable start points at the 2 maze positions, whereas another place group had start points facing the same side of the room. Controls took longer to solve a place problem than the response and direction problems when the start points were not distinguishable. Rats with hippocampal lesions were not different than controls on the response problem but were impaired on the direction and place problems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"Lesions of the Dorsal Hippocampus Block Trace Fear Conditioned Potentiation of Startle": Correction.

Reports an error in the original article "Lesions of the Dorsal Hippocampus Block Trace Fear Conditioned Potentiation of Startle" by Markus Fendt, Michael S. Fanselow, and Michael Koch (Behavioral Neuroscience, 2005, Vol. 119, No. 3, pp. 834-838). On page 834, the Author note contains incorrect affiliation and acknowledgement information. The correct version is presented here. (The following abstract of this article originally appeared in record 2005-06959-021.) Several studies show that the hippocampus is critical for the memories mediating trace and contextual fear conditioning. This study investigates whether N-methyl-D-aspartate-induced lesions of the dorsal hippocampus made prior to training affect context fear conditioning and trace fear conditioning measured with the fear-potentiated startle. Pretraining excitotoxic lesions of the dorsal hippocampus blocked acquisition of trace fear conditioning to a tone stimulus but did not affect context fear conditioning. These data indicate that without a dorsal hippocampus rats are unable to acquire trace conditioning but can acquire contextual fear when fear is measured by potentiation of the startle response. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Learning impairments of hippocampal-lesioned mice in a paddling pool.

Control mice rapidly learned to escape from shallow water in a paddling pool, which combined elements of the Morris water maze and the Barnes holeboard maze. The pool's transparent perimeter wall contained 12 exits, only 1 of which led to an escape tunnel. Learning was impaired in mice with cytotoxic lesions of the hippocampus. Probe trials suggested that the controls were using extramaze cues. When the exit was blocked, controls, but not hippocampals, spent more time searching in this previously correct sector. When the spatial location of the exit was changed, hippocampals escaped more quickly, as they showed no preference for the old location. These results may be useful in the assessment of hippocampal dysfunction, particularly in genetically manipulated mice. (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)     

Effects of Hippocampus and Medial Caudate Nucleus Lesions on Memory for Direction Information in Rats.

A delayed matching-to-sample task was designed to assess memory for direction information in rats. During the study phase, rats traversed a maze arm oriented in 1 of 3 directions. After a delay period, a test phase was presented that required a choice between the study phase direction and a foil direction. Once rats reached a learning criterion, probe trials suggested that normal rats favor the use of direction, rather than turning response, information and use vestibular feedback. Rats were then given hippocampus, medial caudate nucleus (MCN), or cortical control lesions. Unlike control rats, those with hippocampus and MCN lesions exhibited marked impairments when retested. However, all rats were able to learn a direction discrimination task. These results suggest that the hippocampus and MCN support processes associated with short-term memory for direction information. (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)     

Using Idiothetic Cues to Swim a Path With a Fixed Trajectory and Distance: Necessary Involvement of the Hippocampus, but Not the Retrosplenial Cortex.

Rats rapidly learned to find a submerged platform in a water maze at a constant distance and angle from the start point, which changed on every trial. The rats performed accurately in the light and dark, but prior rotation disrupted the latter condition. The rats were then retested after receiving cytotoxic hippocampal or retrosplenial cortex lesions. Retrosplenial lesions had no apparent effect in either the light or dark. Hippocampal lesions impaired performance in both conditions but spared the ability to locate a platform placed in the center of the pool. A hippocampal deficit emerged when this pool-center task was run in the dark. The spatial effects of hippocampal damage extend beyond allocentric tasks to include aspects of idiothetic guidance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)