Selective hippocampal lesions in rats disrupt acquisition and retention of a positive patterning discrimination

To determine the contribution of the hippocampus in the processing of a configural positive patterning discrimination (PPD) task, discrimination between reinforced presentations of a tone plus light compound stimulus and nonreinforced presentations of each of its components (TL+/T-,L-) was examined using a conditioned-suppression paradigm. In the first experiment, rats demonstrated a rapid acquisition of the PPD with an appropriate discriminative responding. Rats submitted to posttraining hippocampal lesions (using multiple injections of ibotenic acid) were no longer able to master correctly the previously solved discrimination, demonstrating significant differences in their response rates during the 2 never-reinforced elemental stimulus presentations. In Experiment II, lesioned rats were not able to correctly learn the PPD, demonstrating the same pattern of responding as in Experiment I. These rats were also severely disrupted in a radial maze elimination task. Experiment IIIa indicated that, in a simple conditioning task (T+, L+), normal rats acquired a rapid conditioned suppression for both stimuli, with the tone being slightly more susceptible to conditioning than the light stimulus. In Experiment IIIb, conditioning to the compound tone plus light stimulus led to a clear conditioning to the tone and almost no conditioning to the light, suggesting an overshadowing from the tone to the light. Similar results were obtained in rats with hippocampal lesions. These results strongly suggest that the disruption showed by rats with hippocampal lesions in the PPD task cannot be due to an alteration of the relative salience of the stimulus. The inability of rats with hippocampal lesions to solve correctly the PPD is due to difficulties in eliminating responding to some unimportant events of the situation, reflecting a deficit in selective attention processes rather than in an ability to process configural stimuli. In the discussion, the putative role of the hippocampus in selective attentional processes is more fully discussed.     

Hippocampal lesions do not impair negative patterning: A challenge to configural association theory.

According to configural association (CAS) theory (R. J. Sutherland and J. W. Rudy; see record 1989-38933-001), an intact hippocampus is required for rats to solve learning problems that are based on "configural" processes. This theory identifies the negative patterning discrimination as a critical example of this type of problem. Rudy and Sutherland (see record 1990-03930-001) reported disruption of negative patterning following hippocampal formation damage produced by intracranial infusion of a mixture of kainic acid?+?colchicine (KA?+?COL). Acquisition of negative patterning was assessed in rats with hippocampal damage produced by KA?+?COL compared with rats with more selective ibotenate lesions of hippocampus. Neither group showed impaired negative patterning relative to controls. A transfer test provided evidence that all groups used configural processes to solve the problem. Thus contrary to CAS theory, the hippocampus is not an important substrate for the operation of configural processes. (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)     

Systematic comparison of the effects of hippocampal and fornix-fimbria lesions on acquisition of three configural discriminations

The effects of lesions to the hippocampal system on acquisition of three different configural tasks by rats were tested. Lesions of either the hippocampus (kainic acid/colchicine) or fornix-fimbria (radiofrequency current) were made before training. After recovery from surgery, rats were trained to discriminate between simple and compound-configural cues that signaled the availability or nonavailability of food when a bar was pressed. When positive cues were present, one food pellet could be earned by pressing a lever after a variable time had elapsed. The trial terminated on food delivery (variable interval 15 s). This procedure eliminates some possible alternative explanations of the results of previous experiments on configural learning. Hippocampal lesions increased rates of responding and retarded acquisition of a negative patterning task (A+, B+, AB-); using a ratio measure of discrimination performance these lesions had a milder retarding effect on a biconditional discrimination (AX+, AY-, BY+, BX-), and they had no effect on a conditional context discrimination (X: A+, B-; Y: A-, B+). Fornix-fimbria lesions did not affect acquisition of any of these tasks but increased rates of responding. The results suggest that several task parameters determine the involvement of the hippocampus in configural learning; however, all tasks tested can also be learned to some extent in the absence of an intact hippocampal system, presumably by other learning/memory systems that remain intact following surgery. The lack of effect of fornix-fimbria lesions on any of these tasks suggests that retrohippocampal connections with other brain areas may mediate hippocampal contributions to the learning of some configural tasks. An analysis of these results and of experiments on spatial learning situations suggests that involvement of the hippocampus is a function of the degree to which correct performance depends on a knowledge of relationships among cues in a situation.     

Unilateral labyrinthectomy downregulates glutamate receptor delta-2 expression in the rat vestibulocerebellum

Subcortical damage in neonates often has more severe consequences than in adults. Unilateral electrolytic hippocampal lesions in adult rats typically result in transient memory deficits, whereas neonatal lesions cause lasting memory impairments. We hypothesized that unilateral lesions made at birth may affect synaptic physiology in the contralateral hippocampus. Consequently, the ability to sustain long-term potentiation (LTP), a form of synaptic plasticity believed to underlie certain forms of memory, was compared between slices from the remaining hippocampus of rats lesioned as newborns and as adults. Initial studies showed that a train of 10 stimulation bursts patterned after the hippocampal theta rhythm produced robust and stable LTP both in slices from controls and rats lesioned at birth. However, a theta burst pattern of stimulation closer to intrinsic physiology (five burst pairs separated by 30 s each), induced significantly less LTP in slices from rats lesioned at birth compared to those from controls and rats lesioned as adults. To investigate possible mechanisms underlying the deficit, the degree of paired-pulse facilitation (PPF) as well as the amount of depolarization occurring between two successive theta bursts were analyzed. The lesion did not detectably change PPF characteristics, suggesting that presynaptic mechanisms are normal. However, the extent to which a burst response was increased by a prior burst was significantly diminished in slices from rats lesioned at birth compared to those from controls and rats lesioned as adults, indicating that postsynaptic factors involved in the initial triggering events of LTP are affected by the lesion. Reduced ability to sustain LTP in the remaining hippocampus may contribute to impaired memory function after unilateral neonatal hippocampal lesion.     

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)     

Discriminating the stimulus elements during human odor–taste learning: A successful analytic stance does not eliminate learning.

Odor “sweetness” may arise from experiencing odors and tastes together, resulting in a flavor memory that is later reaccessed by the odor. Forming a flavor memory may be impaired if the taste and odor elements are apparent during exposure, suggesting that configural processing may underpin learning. Using a new procedure, participants made actual flavor discriminations for one odor–taste pair (e.g., Taste A vs. Odor X–Taste A) and mock discriminations for another (e.g., Odor Y–Taste B vs. Odor Y–Taste B). Participants, who were successful at detecting the actual flavor discriminations, demonstrated equal amounts of learning for both odor–taste pairings. These results suggest that although a capacity to discriminate flavor into its elements may be necessary to support learning, whether participants experience a configural or elemental flavor representation may not. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Rats with fimbria-fornix lesions can acquire and retain a visual-tactile transwitching (configural) task.

The idea that the hippocampus is essential for acquisition and retention of a transwitching (configural) problem is evaluated with a visual-tactile task. The task requires the rats to pull up a string of one of two sizes for food, as signalled by room lighting conditions. Rats received cathodal fimbria-fornix lesions either prior to or after learning the task. Rats with fimbria-fornix lesions were unimpaired in acquisition or retention. The results do not support the position that the hippocampal formation is essential for the acquisition and retention of a transwitching configural problem. The result is discussed in relation to the configural theory of hippocampal function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampal seizures disrupt working memory performance but not reference memory acquisition.

The effect of hippocampal seizures in rats was assessed in two spatial memory tasks: The reference memory task was a simultaneous two-choice discrimination in a T-maze. The working memory task was a delayed conditional discrimination in a radial arm maze. In each task the hippocampus of each rat was stimulated to seizure after the presentation of the information to be remembered. In the reference memory task, hippocampal seizures did not impair acquisition, whether the stimulation was given immediately after or 4 hr after the presentation of the stimuli to be remembered. In the working memory task, hippocampal seizures did impair performance in a group of the same rats. These results support the distinction between a trial-dependent working memory system that requires hippocampal function and a trial-independent memory system that does not depend on hippocampal function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Amphetamine disrupts negative patterning but does not produce configural association deficits on an alternative task

Three experiments investigated the effects of d-amphetamine on the performance of rats on tasks that required the discrimination of configural cues (i.e., those in which two stimulus elements, tone and light, have a meaning when presented together that is distinct from the meaning of the same elements presented in isolation from each other). In a negative patterning task (Experiment 1), rats were trained in a GO/NO-GO task in which either stimulus alone signalled reward availability whilst the compound did not. Amphetamine (0.5, 1.0 and 2.0 mg/kg) was found to disrupt performance by increasing responses to the unrewarded compound. Responses were also increased during the ITI. In contrast, in Experiments 2 and 3 amphetamine had little impact on performance on a task in which the rats had to respond to either of the single stimuli with one response (lever-press or chain-pull) and to the compound stimulus with the other response. The results add credence to the suggestion of Davidson et al. (Behav. Neurosci., 1993, 107, 227-234) that hippocampal lesions disrupt negative patterning by increasing responsiveness rather than by disrupting a configural association system and do not support the idea that increased dopamine activity disrupts configural associations. The findings are discussed in the context of hippocampal-dopamine interactions.     

The hippocampus and memory for orderly stimulus relations

Human declarative memory involves a systematic organization of information that supports generalizations and inferences from acquired knowledge. This kind of memory depends on the hippocampal region in humans, but the extent to which animals also have declarative memory, and whether inferential expression of memory depends on the hippocampus in animals, remains a major challenge in cognitive neuroscience. To examine these issues, we used a test of transitive inference pioneered by Piaget to assess capacities for systematic organization of knowledge and logical inference in children. In our adaptation of the test, rats were trained on a set of four overlapping odor discrimination problems that could be encoded either separately or as a single representation of orderly relations among the odor stimuli. Normal rats learned the problems and demonstrated the relational memory organization through appropriate transitive inferences about items not presented together during training. By contrast, after disconnection of the hippocampus from either its cortical or subcortical pathway, rats succeeded in acquiring the separate discrimination problems but did not demonstrate transitive inference, indicating that they had failed to develop or could not inferentially express the orderly organization of the stimulus elements. These findings strongly support the view that the hippocampus mediates a general declarative memory capacity in animals, as it does in humans.     

Temporally graded retrograde amnesia of contextual fear after hippocampal damage in rats: within-subjects examination

We have shown previously that electrolytic lesions of the dorsal hippocampus (DH) produce a severe deficit in contextual fear if made 1 d, but not 28 d, after fear conditioning (). As such, the hippocampus seems to play a time-limited role in the consolidation of contextual fear conditioning. Here, we examine retrograde amnesia of contextual fear produced by DH lesions in a within-subjects design. Unlike our previous reports, rats had both a remote and recent memory at the time of the lesion. Rats were given 10 tone-shock pairings in one context (remote memory) and 10 tone-shock pairings in a distinct context (with a different tone) 50 d later (recent memory), followed by DH or sham lesions 1 d later. Relative to controls, DH-lesioned rats exhibited no deficit in remote contextual fear, but recent contextual fear memory was severely impaired. They also did not exhibit deficits in tone freezing. This highly specific deficit in recent contextual memory demonstrated in a within-subjects design favors mnemonic over performance accounts of hippocampal involvement in fear. These findings also provide further support for a time-limited role of the hippocampus in memory storage.     

Perirhinal Cortex and Anterior Thalamic Lesions: Comparative Effects on Learning and Memory.

Three learning and memory tasks were used to compare the effects of neurotoxic anterior thalamic nuclei (ATN) and perirhinal cortex (PRC) lesions in rats. Rats with ATN lesions showed impaired spatial memory in a 12-arm radial maze, whereas rats with PRC lesions showed intact spatial memory, despite the use of minimal pretraining and extensive within-session delays (to 40 rain). PRC, but not ATN, lesions produced impairments on a configural learning task using complex visual-tactile cues in the radial maze. Neither ATN nor PRC lesions consistently affected spontaneous object recognition across extended sample-test delays (to 40 min). These findings confirm the differential involvement of the ATN and PRC in learning and memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the rat perirhinal cortex spare the acquisition of a complex configural visual discrimination yet impair object recognition.

Rats with perirhinal cortex lesions were sequentially trained in a rectangular water tank on a series of 3 visual discriminations, each between mirror-imaged stimuli. When these same discriminations were tested concurrently, the rats were forced to use a configural strategy to solve the problems effectively. There was no evidence that lesions of the perirhinal cortex disrupted the ability to learn the concurrent configural discrimination task, which required the rats to learn the precise combination of stimulus identity with stimulus placement (“structural” learning). The same rats with perirhinal cortex lesions were also unimpaired on a test of spatial working memory (reinforced T maze alternation), although they were markedly impaired on a new test of spontaneous object recognition. For the recognition test, rats received multiple trials within a single session in which on every trial, they were allowed to explore 2 objects, 1 familiar, the other novel. On the basis of their differential exploration times, rats with perirhinal cortex lesions showed very poor discrimination of the novel objects, thereby confirming the effectiveness of the surgery. The discovery that bilateral lesions of the perirhinal cortex can leave configural (structural) learning seemingly unaffected points to a need to refine those models of perirhinal cortex function that emphasize its role in representing conjunctions of stimulus features. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rats with damage to the hippocampal-formation are impaired on the transverse-patterning problem but not on elemental discriminations.

We assessed the effects of hippocampal-formation (HF) damage on the rat's ability to learn two sets of concurrent visual discriminations. Each set included three problems. One set, called the transverse-patterning problem, was constructed so that each choice stimulus was ambiguous; sometimes it was the correct (+) and sometimes it was the incorrect (–) choice as follows: A+ vs B–, B+ vs C–, and C+ vs A–. It could not be solved unless rats used configural associations. The stimuli were not ambiguous in the second, elemental problem set, A+ vs B–, C+ vs D–, and E+ vs F–. Rats could solve this set without the use of configural associations. Rats with HF damage solved the set of elemental problems, but their performance on the transverse-patterning problem was impaired. These results support Sutherland and Rudy's (see record 1989-38933-001) theory that the hippocampal formation is critical for the acquisition of configural associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Configural and elemental strategies in predictive learning.

When 2 cues occur together and reliably predict an outcome, Ss often judge the effect of the compound as reducible to the individual effects of the elements. This elemental processing in predictive learning is perhaps the single most important aspect of most theories of human inference. Surprisingly, selectional processing was not observed in either blocking or conditioned inhibition problems. Only when the learner had past experience with another problem encouraging an elemental strategy were the expected selectional processes observed. These proactive effects of prior learning were abolished if the earlier problem required a nonadditive solution. The results suggest that configural cues were guiding predictive inferences in the absence of elemental processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contextual fear discrimination is impaired by damage to the postrhinal or perirhinal cortex.

Postrhinal (POR) or perirhinal (PER) cortex damage impairs acquisition and expression of contextual fear, but the nature of the impairment remains unclear. This study used a contextual fear discrimination paradigm that biased subjects toward using a configural, rather than an elemental, strategy to distinguish between 2 contexts, 1 of which was paired with a mild footshock. Control rats discriminated between 2 contexts when a combination of several cues could be used (Exp 1), but not when individual sensory cues were manipulated (Exp 2). Rats with POR or PER lesions could not discriminate between the shock and no-shock contexts when multiple cues differentiated the contexts (Exp 3). The results indicate that both the POR and PER have a role in configural learning of contextual fear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Some properties of configural learning: An investigation of the transverse-patterning problem.

Little is known about the conditions that encourage animals to learn to use configural associations to guide their behavior or the consequences of such learning for transfer. This study provided some information about these issues by examining how rats solve the transverse-patterning problem, which requires a configural solution (K. W. Spence, 1952). Animals had to concurrently solve 3 simultaneous visual discriminations, represented abstractly as A+ vs B–, B+ vs C–, and C+ vs A–. Exp 1 indicated that rats use a configural solution even when the problems have an elemental solution, provided that the significance of 1 element (e.g., B) shared by 2 problems is ambiguous (e.g., A+/B–; and B+/C–). Exps 2 and 3 suggested that, when stimulated to use a configural solution by solving the A+/B– and B+/C– problems, rats transfer the configural solution to problems that have no ambiguous elements. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Learning theory and neuropsychology: Configuring their disparate elements in the hippocampus.

Using the contrast of elemental and configural theories of learning, some of the major differences in the assumptions that underlie neuropsychological approaches to memory and learning theoretical approaches are illustrated. Both strategies are shown to have different advantages and shortcomings. It is argued that future progress will succeed best by synthesizing features of both types of analysis. To provide evidence for this argument, it is suggested that both elemental and configural conditional stimuli processing systems exist and that they interact by competitive associational rules. This type of approach receives convergent support from both environmental manipulations; neuroanatomy and examination of brain-damaged subjects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Separability and integrality of global and local levels of hierarchical patterns.

Used a constrained classification task to examine the perceptual relations between global and local levels in hierarchical patterns composed of many, relatively small elements and those composed of few, relatively large elements. In 4 experiments, 52 18–35 yr olds made classifications based on form or texture or according to the shape of the configuration or the elements. Results indicate that configural and elemental levels were perceptually separable for many-element patterns when processed as form and texture. Ss could attend to either level without being affected by variation along the irrelevant dimension. However, when the same many-element patterns were processed for global and local shape. Ss could not selectively attend to either level. For few-element patterns, global configuration and local elements appeared to be perceptually integral dimensions. Results are discussed in terms of the global precedence hypothesis and explanations of integral and separable dimensions. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)