Delayed extinction attenuates conditioned fear renewal and spontaneous recovery in humans.

This study investigated whether the retention interval after an aversive learning experience influences the return of fear after extinction training. After fear conditioning, participants underwent extinction training either 5 min or 1 day later and in either the same room (same context) or a different room (context shift). The next day, conditioned fear was tested in the original room. When extinction took place immediately, fear renewal was robust and prolonged for context-shift participants, and spontaneous recovery was observed in the same-context participants. Delayed extinction, by contrast, yielded a brief form of fear renewal that reextinguished within the testing session for context-shift participants, and there was no spontaneous recovery in the same-context participants. The authors conclude that the passage of time allows for memory consolidation processes to promote the formation of distinct yet flexible emotional memory traces that confer an ability to recall extinction, even in an alternate context, and minimize the return of fear. Furthermore, immediate extinction can yield spontaneous recovery and prolong fear renewal. These findings have potential implications for ameliorating fear relapse in anxiety disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impaired processing of local geometric features during navigation in a water maze following hippocampal lesions in rats.

Hippocampal damage impairs navigation with respect to information provided by the shape of an arena. Recent evidence has suggested that normal rats use local geometric information, as opposed to a global geometric representation, to navigate to a correct corner. One implication of this pattern of results is that hippocampal lesions may impair processing of 1 or more of the local geometric features of an environment. The authors therefore investigated the effects of hippocampal cell loss in rats on navigation to a hidden goal with respect to a variety of local cues in an environment with a distinctive shape. Rats with lesions of the hippocampus were impaired in discriminating a right-angled corner from its mirror image. However, they were able to use cues provided by an acute-angled corner (Experiment 1) or a local polarizing cue (Experiment 2). In contrast, lesioned rats were impaired in discriminating long versus short walls (Experiment 3). Results indicate that the hippocampus plays a role in disambiguating locations by processing (metric) information related to the distance between corners. (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)     

Renewal and spontaneous recovery, but not latent inhibition, are mediated by gamma-aminobutyric acid in appetitive conditioning.

Previous research has reported a role for the neurotransmitter gamma-aminobutyric acid (GABA) in the extinction and renewal of conditioned fear. Here, the authors examine whether GABA is involved in the acquisition, extinction, renewal, spontaneous recovery, and latent inhibition of appetitive conditioning. Using Long-Evans rats, systemic injection of the GABA A receptor inverse agonist FG 7142 was shown to eliminate ABA renewal (Experiment 1) and spontaneous recovery (Experiment 4) of appetitive responding by selectively reducing the recovery of extinguished magazine approach. Furthermore, treatment with FG 7142 had no effects on acquisition or single-session extinction (Experiment 3) or on the context-specific expression of latent inhibition (Experiment 2). These data suggest that ABA renewal and spontaneous recovery, but not latent inhibition or responding during acquisition and an initial extinction session, are mediated by GABAergic mechanisms in appetitive Pavlovian conditioning. They provide support for the view that renewal and spontaneous recovery share a common psychological mechanism. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Beacon training in a water maze can facilitate and compete with subsequent room cue learning in rats.

In Stage 1 of 4 experiments in which rats completed a water-maze blocking procedure, experimental groups were trained to use a predictive beacon (hanging above, connected to, or displaced from the platform) to find a submerged escape platform in the presence of predictive or irrelevant background cues and in the presence or absence of irrelevant landmarks. In Stage 2, a fixed beacon, landmarks, and background cues all predicted the platform location. A Room Test (landmarks and background cues only) showed that Stage 1 training with a fixed hanging beacon or the moving displaced beacon facilitated Stage 2 learning of predictive room cues for experimental relative to control subjects. In contrast, Stage 1 training with a moving pole beacon interfered with Stage 2 learning about predictive room cues relative to controls, whereas training with a fixed pole or moving hanging beacon had no effect. We conclude that multiple spatial learning processes influence locating an escape platform in the water maze. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evidence for a shift from place navigation to directional responding in one variant of the Morris water task.

Previous work from our laboratory has demonstrated that rats display a preference for directional responding over place navigation in a wide range of procedural variants of the Morris water task (Hamilton, Akers, Weisend, & Sutherland, 2007; Hamilton et al., 2008). A preference for place navigation has only been observed when the pool is reduced as a cue by filling it with water. Studies using dry land mazes have suggested that rats place navigate early in training and later switch to other forms of responding (e.g., motor). The present study evaluated whether rats switch from place navigation to directional responding in the “full-pool” variant of the water task. Rats were given 12, 24, or 36 hidden platform training trials. Probe trials with the pool repositioned in the room revealed a preference for place navigation in rats given 12 trials, an equal division of response preferences in rats given 24 trials, and a preference for directional responding in rats given 36 trials. These results indicate that the early preference for place navigation in the full-pool water task is transient and yields to a preference for directional responding with continued training. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spontaneous recovery but not reinstatement of the extinguished conditioned eyeblink response in the rat.

Reinstatement—the return of an extinguished conditioned response (CR) after reexposure to the unconditioned stimulus (US)—and spontaneous recovery—the return of an extinguished CR with the passage of time—are 2 of 4 well-established phenomena that demonstrate that extinction does not erase the conditioned stimulus (CS)–US association. However, reinstatement of extinguished eyeblink CRs has never been demonstrated, and spontaneous recovery of extinguished eyeblink CRs has not been systematically demonstrated in rodent eyeblink conditioning. In Experiment 1, US reexposure was administered 24 hr prior to a reinstatement test. In Experiment 2, US reexposure was administered 5 min prior to a reinstatement test. In Experiment 3, a long, discrete cue (a houselight), present in all phases of training and testing, served as a context within which each trial occurred to maximize context processing, which in other preparations has been shown to be required for reinstatement. In Experiment 4, an additional group was included that received footshock exposure, rather than US reexposure, between extinction and test, and contextual freezing was measured prior to test. Spontaneous recovery was robust in Experiments 3 and 4. In Experiment 4, context freezing was strong in a group given footshock exposure but not in a group given eye shock US reexposure. There was no reinstatement observed in any experiment. With stimulus conditions that produce eyeblink conditioning and research designs that produce reinstatement in other forms of classical conditioning, we observed spontaneous recovery but not reinstatement of extinguished eyeblink CRs. This suggests that reinstatement, but not spontaneous recovery, is a preparation- or substrate-dependent phenomenon. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Similarities and differences in spatial learning and object recognition between young male C57Bl/6J mice and Sprague-Dawley rats.

Mice and rats are often used interchangeably in neuroscience research. However, species differences in brain structure and connectivity exist within the medial temporal lobe circuits that contribute to learning and memory. The hippocampus in particular contributes to both spatial learning and recognition memory, but the extent to which rats and mice are comparable in these two cognitive domains remains unclear. To evaluate potential species differences in spatial memory and object recognition, young adult male Sprague–Dawley rats and male C57Bl/6J mice were tested in the water maze and novel object recognition tasks. Following six days of training, with four trials per day, there was no difference in the ability of rats and mice to learn the location of a hidden platform. However, rats performed better than mice on the probe trial, indicative of superior retention. In the novel object preference test, no species differences in recognition memory were detected, although rats spent more time exploring the arena and took longer to approach the objects. These observations suggest that while species differences in spatial memory retention are present, they do not correlate with differences in object recognition memory. (PsycINFO Database Record (c) 2011 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)     

Age-related deficits in mice performing working memory tasks in a water maze.

This study determined whether mice exhibit spatial working memory deficits with increased age. C57BL/6JNia mice of 3 different ages were tested in the Morris water maze with 2 protocols designed to assess immediate and delayed working memory abilities. Young mice required multiple trials in order to show improvements in the working memory task. Deficits in immediate working memory were detected in both 10- and 24- to 26-month-old mice. Reference memory deficits and declines in performance in the delayed working memory task were only seen in 24- to 26-month-olds. This increased susceptibility of immediate working memory processes to the aging process in mice may be related to their need for more rehearsal in the water maze than other species. (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 to Oswald et al. (2003).

Reports an error in "Entorhinal cortex lesions disrupt the transition between the use of intra- and extramaze cues for navigation in the water maze" by C. J. P. Oswald, D. M. Bannerman, B. K. Yee, J. N. P. Rawlins, R. C. Honey and M. Good (Behavioral Neuroscience, 2003[Jun], Vol 117[3], 588-595). 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. (The following abstract of the original article appeared in record 2003-05069-018.) 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 relative influence of place and direction in the Morris water task.

Previous work from our laboratory has demonstrated that rats display a preference for directional responding over true place navigation in the Morris water task. The present study evaluated the range of situations in which this preference is observed and attempted to identify methods that favor navigation to the precise location of the escape platform in the room. A preference for directional responding over place navigation was observed in a wide range of procedures that included providing extensive training (Experiment 1), providing only platform placement experience in the absence of active swim training (Experiment 2), training navigation to multiple platform locations in a moving platform variant of the task (Experiment 3), and explicitly training navigation to a precise location in the room, versus navigation in a particular direction, regardless of the pool's position in the room (Experiments 4-5). A modest preference for navigation to the precise spatial location of the platform was observed when the pool wall was virtually eliminated as a source of control by filling it to the top with water (Experiment 6). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An analysis of response, direction and place learning in an open field and T maze.

Rats were trained to locate food in a response, direction, or place problem on an open field located at 2 positions. In Experiment 1, both the response and direction groups solved the problem. The place group failed to solve the task in approximately 300 trials. Experiment 2 demonstrated that rats need distinguishable start points to solve a place problem when neither a response nor a direction solution is available. Findings from Experiment 3 suggest that a combination of path traveled and distinct cues help to differentiate start points. Experiment 4 replicated the findings using a T maze. These results suggest 'place' solutions are difficult for rats. The data are discussed with respect to conditional learning and modem spatial mapping theory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

GluR-A-deficient mice display normal acquisition of a hippocampus-dependent spatial reference memory task but are impaired during spatial reversal.

Acquisition and reversal of a spatial discrimination were assessed in an appetitive, elevated plus-maze task in 4 groups of mice: knockout mice lacking the AMPA receptor subunit GluR-A (GluR1), wild-type controls, mice with cytotoxic hippocampal lesions, and controls that had undergone sham surgery. In agreement with previous studies using tasks such as the water maze, GluR-A-/- mice were unimpaired during acquisition of the spatial discrimination task, whereas performance in the hippocampal group remained at chance levels. In contrast to their performance during acquisition, the GluR-A-/- mice displayed a mild deficit during reversal of the spatial discrimination and were profoundly impaired during discrete trial, rewarded-alternation testing on the elevated T maze. The latter result suggests a short-term. flexible spatial working memory impairment in GluR-A-/- mice, which might also underlie their mild deficit during spatial reversal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increased spontaneous recovery with increases in conditioned stimulus alone exposures.

A series of experiments used the compound test procedure (Rescorla, 2002) to measure the size of spontaneous recovery of freezing responses by rats to a latently inhibited and/or extinguished conditioned stimulus (CS). The size of recovery was greater: to a pre-exposed and conditioned CS than to a CS just conditioned or just pre-exposed; to an extensively pre-exposed or extinguished CS than to a moderately pre-exposed or extinguished CS; and to a pre-exposed and extinguished CS than to a CS just pre-exposed or just extinguished. These results show that the size of recovery is proportional to the size of the depression produced by CS-alone exposures regardless of whether they occurred before, after, or both before and after conditioning. The results are discussed in terms of some contemporary models of recovery and of the inferences permitted by the use of the compound assessment technique. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Altered performance of reelin-receptor ApoER2 deficient mice on spatial tasks using the Barnes maze.

The apolipoprotein E receptor 2 (ApoER2), expressed predominantly in forebrain regions including the hippocampus, is 1 of 2 receptors for the extracellular matrix protein reelin, which is critical for cortical development. Previous studies of ApoER2 mutant mice have indicated deficits in synaptic plasticity and learning. The current authors assessed learning and memory of ApoER2 knockout and wild-type mice on the Barnes circular maze. Mice were trained in this task for 22 days, followed by memory recall and reversal tests. ApoER2 knockout mice were initially slower to complete the task, but by Day 22 they were more accurate than wild-type mice on several indices. There were no differences in memory assessed by the recall task, but ApoER2 knockout mice performed significantly worse on the memory reversal task. ApoER2 knockout mice also displayed altered use of specific search strategies and relationship of these strategies to errors made on the maze. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial memory deficits in a virtual radial arm maze in amnesic participants with hippocampal damage.

Extensive research with laboratory animals indicates that the hippocampus is crucial for the formation and use of spatial memory. Hippocampal lesions in rodents impair spatial memory on radial arm maze tasks. It is unknown whether amnesic patients with hippocampal damage would exhibit similar impairments on a virtual version of a radial arm maze. To evaluate the importance of the hippocampus in spatial learning and memory, we tested amnesic participants with hippocampal damage in a virtual radial arm maze environment. The virtual radial arm maze required participants to learn and remember 4 rewarded arms of 8 total arms. Spatial learning and memory were assessed using the participants' ability to use salient distal cues in the virtual room to remember the 4 rewarded arms. Amnesic participants' latencies were longer and distance traveled was greater to the rewarded arms compared with nonamnesic participants. Amnesic participants made more errors than nonamnesic participants by either entering nonrewarded arms or by revisiting previously entered arms. These data are analogous to previous animal research. Overall, the human hippocampus is necessary for spatial memory and navigation in a virtual radial arm maze task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modafinil and memory: Effects of modafinil on Morris water maze learning and Pavlovian fear conditioning.

Modafinil has been shown to promote wakefulness and some studies suggest the drug can improve cognitive function. Because of many similarities, the mechanism of action may be comparable to classical psychostimulants, although the exact mechanisms of modafinil's actions in wakefulness and cognitive enhancement are unknown. The current study aims to further examine the effects of modafinil as a cognitive enhancer on hippocampus-dependent memory in mice. A high dose of modafinil (75 mg/kg ip) given before training improved acquisition on a Morris water maze. When given only before testing, modafinil did not affect water maze performance. We also examined modafinil (0.075 to 75 mg/kg) on Pavlovian fear conditioning. A low dose of pretraining modafinil (0.75 mg/kg) enhanced memory of contextual fear conditioning (tested off-drug 1 week later) whereas a high dose (75 mg/kg) disrupted memory. Pretraining modafinil did not affect cued conditioning at any dose tested, and immediate posttraining modafinil had no effect on either cued or contextual fear. These results suggest that modafinil's effects of memory are more selective than amphetamine or cocaine and specific to hippocampus-dependent memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rats (Rattus norvegicus) in a water maze learn both an egocentric trajectory and landmarks.

In two experiments we investigated the extent to which rats (Rattus norvegicus) use an egocentric trajectory and landmarks to locate a goal. In Experiment 1 we trained groups to locate the hidden platform in a water maze with either 1 of 3 or 3 of 3 predictive landmarks, and with either a random or fixed egocentric trajectory. A choice test revealed that regardless of the landmark configuration, rats relied on a directional, egocentric trajectory, when it was available, to locate the platform. In Experiment 2 we found that adding four predictive landmarks following training with a constant egocentric trajectory did not alter rats' initial attention to the trajectory. We conclude that the presence of nonpredictive landmarks in a predictive array did not affect the use of landmarks. With a blocking design, rats used initially an egocentric path, then landmarks. These results add to the notion that animals use available spatial cues sequentially. (PsycINFO Database Record (c) 2010 APA, all rights reserved)