Discrimination of what,when, and where: Implications for episodic-like memory in rats

We investigated the discrimination of what, when, and where in rats (n = 5) using an eight-arm radial maze. Rats received daily training consisting of forced-choice visits to four baited arms, one of which was randomly chosen each day to contain chocolate (Phase 1). In Phase 2, all eight arms were available. After a short (30 min) retention interval (RI), the four arms that were not available in Phase 1 provided food. After a long (4 h) RI, the four remaining arms plus the arm containing chocolate provided food (i.e., the chocolate arm replenished). The rats visited the chocolate location after the long RI more than after the short RI. Next, chocolate was paired with lithium chloride, and subsequent testing used the long RI. The rats visited the chocolate location less after the taste-aversion manipulation than in previous training, demonstrating knowledge of what, when, and where. Implications for episodic-like memory are discussed.     

Scrub jays (Aphelocoma coerulescens) form integrated memories of the multiple features of caching episodes

Four experiments examined whether food-storing scrub jays remember when and where they cached different foods. The scrub jays cached and recovered perishable and nonperishable foods in visuospatially distinct and trial-unique cache sites. They rapidly learned to avoid searching for foods that had perished by the time of recovery, while continuing to search for the same foods after shorter retention intervals when the foods were still fresh. The temporal control of searching at recovery was also observed when the familiarity of cache sites did not provide any information about the time of caching and when the same food was cached in distinct sites at different times. The authors argue that the jays formed an integrated memory for the location and time of caching of particular foods.     

Scrub jays (Aphelocoma coerulescens) remember the relative time of caching as well as the location and content of their caches

Two experiments examined whether food-storing scrub jays (Aphelocoma coerulescens) could remember when they cached particular food items as well as what they cached and where. In Experiment 1, scrub jays cached and recovered perishable "wax worms" (wax moth larvae) and nonperishable peanuts in 2 visuospatially distinct and trial-unique trays. The birds searched preferentially for fresh wax worms if they had cached them 4 hr earlier but rapidly learned to search for peanuts and avoid decayed wax worms that had been cached 124 hr previously. This pattern also was observed when the food items were removed before recovery on test trials. These results were replicated in Experiment 2 using a procedure in which both types of food were cached in different sides of the same caching tray: On the basis of a single, trial-unique experience, scrub jays could remember the relative time of caching as well as what type of food was cached in each cache site.     

The control of food-caching behavior by Western scrub-jays (Aphelocoma californica)

Western scrub-jays (Aphelocoma californica) did not show extinction when caching behavior was never rewarded and they had no choice of where to cache the food. However, when the jays had the choice of caching items in 2 different locations or during 2 successive episodes, and only 1 of each was always rewarded at recovery, they rapidly learned to cache in the rewarded location or episode. When the jays had learned during training trials that their caches were always moved to 1 of 2 locations they did not cache in, then on the test trial they cached in the location that had been previously rewarded. To test whether these jays avoided the location in which their caches had been pilfered or chose the rewarded location, the procedure was repeated to include a 3rd location that was never rewarded. The jays avoided the pilfered location but cached equally in the rewarded and nonrewarded locations.     

Western scrub-jays (<Emphasis Type="Italic">Aphelocoma californica</Emphasis>) use cognitive strategies to protect their caches from thieving conspecifics

Food caching birds hide food and recover the caches when supplies are less abundant. There is, however, a risk to this strategy because the caches are susceptible to pilfering by others. Corvids use a number of different strategies to reduce possible cache theft. Scrub-jays with previous experience of pilfering other's caches cached worms in two visuospatially distinct caching trays either in private or in the presence of a conspecific. When these storers had cached in private, they subsequently observed both trays out of reach of a conspecific. When these storers had cached in the presence of a conspecific, they subsequently watched the observer pilfering from one of the trays while the other tray was placed in full view, but out of reach. The storers were then allowed to recover the remaining caches 3 h later. Jays cached more worms when they were observed during caching. At the time of recovery, they re-cached more than if they had cached in private, selectively re-caching outside of the trays in sites unbeknown to potential thieves. In addition, after a single pilfering trial, the jays switched their recovery strategy from predominantly checking their caches (i.e. returning to a cache site to see whether the food remained there) to predominantly eating them. Re-caching remained constant across the three trials. These results suggest that scrub-jays use flexible, cognitive caching and recovery strategies to aid in reducing potential future pilfering of caches by conspecifics.     

Effects of anesthetic agents on socially transmitted olfactory memories in mice

Mice can learn a food preference from odor cues transmitted on the breath of a conspecific, even if the “demonstrator” is anesthetized. To our knowledge there are no studies examining the effect of anesthetizing the “observer” on development of memory for socially transmitted food preferences (STFP). In Experiment 1 we found that 2–4 month-old F2 C57Bl/6x129sv male and female mice demonstrated a STFP after a 5 min exposure to an anesthetized demonstrator mouse when tested 24 h later. In Experiment 2, observer mice anesthetized with Sagatal (60 mg/kg) prior to the “social interaction” preferentially avoided the cued food when tested 24 h later. This aversion was not due to any overt aversive effects of this dose of Sagatal because mice that ate the food and were then anesthetized, or could only smell the food for 5 min while anesthetized, showed no preference or aversion. In a third experiment we found that the Sagatal-induced aversion was not a general property of anesthesia because there were varied results produced by observer mice treated with anesthetic drugs with different mechanisms of action. Vetalar (200 mg/kg) and Rompun (10 mg/kg) treated animals ate similar amounts of cued and non-cued food at test, indicating an absence of learning. Hypnorm (0.5 ml/kg) treated animals showed a preference for the cued food whereas those treated with Hypnovel (2.5 ml/kg) showed an aversion to the cued food. These results show that the food aversion observed with Sagatal is not a general property of anesthetic agents, but appears to be restricted to those acting primarily on the GABAergic system. Thus, we have shown that under certain conditions it is possible for an anesthetized observer mouse to learn a preference or aversion of a socially-linked olfactory cue.     

Establishment of a schizophrenic animal model through chronic administration of MK-801 in infancy and social isolation in childhood

BackgroundAlthough an increasing amount of evidence supports a “two-hit” hypothesis for the neurodevelopmental model of schizophrenia, there has been no development in animal models to test this hypothesis.MethodsAn animal model was established by chronic administration of 0.1, 0.3, and 0.5 mg/kg MK-801 in P7-P21 rats followed by four weeks of social isolation in childhood and then five days of social housing. Animal behaviors were measured by the open field (OF) test, the novel object recognition (NOR) test, the prepulse inhibition (PPI) test, and the elevated plus maze (EPM) test.ResultsWe found a significant decrease in the NOR index in adolescent rats compared to saline control rats when administering 0.5 mg/kg of MK-801 (P = 0.02). We found that social isolation had no significant effect on NOR index, though social isolation significantly increased the total distance traveled and significantly decreased the resting time in adolescent rats in the OF test (P < 0.001 and P = 0.003, respectively). In contrast, we observed that MK-801 administration showed no significant effects on either total distance traveled or resting time. Both MK-801 administration and social isolation had no significant effect on the percent of PPI and startle amplitudes in adolescent rats. Social isolation significantly reduced the open arm entries in adolescent rats in the EPM test (P = 0.023), but it did not reduce the ratio to enter the open arms and the stay time in open arm. Administration of MK-801 showed no significant effect on the indexes of entering the open arms in the EPM test on adolescent rats.ConclusionMK-801 intervention in infancy is associated with the damage of long-term visual memory, whereas social isolation in childhood is associated with the increased spontaneous activity and anxiety levels. Administration of MK-801 in infancy and social isolation in childhood are two independent factors on the neurodevelopmental defects.     

Dorsal hippocampus function in learning and expressing a spatial discrimination

Learning to discriminate between spatial locations defined by two adjacent arms of a radial maze in the conditioned cue preference paradigm requires two kinds of information: latent spatial learning when the rats explore the maze with no food available, and learning about food availability in two spatial locations when the rats are then confined in one arm with food and the other with no food. Previous research showed that a functional dorsal hippocampus is not required for latent learning. The present experiments show that it is required for learning about food availability, and during retrieval of both types of information.     

Eurasian jays (Garrulus glandarius) conceal caches from onlookers

Animals that cache food risk having their stored food pilfered by conspecifics. Previous research has shown that a number of food-caching species of corvid use strategies that decrease the probability of conspecifics pilfering their caches. In this experiment, we investigated whether Eurasian jays (Garrulus glandarius) would choose between caching behind an opaque and caching behind a transparent barrier whilst being observed by a conspecific. If caching in out-of-sight locations is a strategy to prevent conspecifics from pilfering these caches, then the jays should place a greater proportion of caches behind the opaque barrier when being observed than when caching in private. In accordance with this prediction, jays cached a greater proportion of food behind the opaque barrier when they were observed than when they cached in private. These results suggest that Eurasian jays may opt to cache in out-of-view locations to reduce the likelihood of conspecifics pilfering their caches.     

Audience effects on food caching in grey squirrels (<Emphasis Type="Italic">Sciurus carolinensis</Emphasis>): evidence for pilferage avoidance strategies

If food pilferage has been a reliable selection pressure on food caching animals, those animals should have evolved the ability to protect their caches from pilferers. Evidence that animals protect their caches would support the argument that pilferage has been an important adaptive challenge. We observed naturally caching Eastern grey squirrels (Sciurus carolinensis) in order to determine whether they used any evasive tactics in order to deter conspecific and heterospecific pilferage. We found that grey squirrels used evasive tactics when they had a conspecific audience, but not when they had a heterospecific (corvid) audience. When other squirrels were present, grey squirrels spaced their caches farther apart and preferentially cached when oriented with their backs to other squirrels, but no such effect was found when birds were present. Our data provide the first evidence that caching mammals are sensitive to the risk of pilferage posed by an audience of conspecifics, and that they utilise evasive tactics that should help to minimise cache loss. We discuss our results in relation to recent theory of reciprocal pilferage and compare them to behaviours shown by caching birds.     

Spatial memory for food hidden by rats (Rattus norvegicus) on the radial maze: studies of memory for where,what, and when

Rats (Rattus norvegicus) were allowed to hide food items on an 8-arm radial maze by carrying the items from the center to boxes at the end of each arm. Retrieval tests given after rats had hidden 4 items showed that they selectively returned to the maze arms where food had been hidden (Experiments 1 and 2). When rats were allowed to hide pieces of cheese (refed food) and pretzels (less preferred food) on different arms, they both hid and retrieved cheese before pretzels (Experiments 2-5). In Experiment 6, rats chose between arms where cheese and pretzels were hidden,with cheese degraded at one delay interval but not the other. Together, these experiments indicate memory for what and where but not when.     

Reacquisition of heroin and cocaine place preference involves a memory consolidation process sensitive to systemic and intra-ventral tegmental area naloxone

To investigate the effect of naloxone on a putative memory consolidation process underlying reacquisition of heroin and cocaine conditioned place preference, four studies were conducted in male Sprague–Dawley rats using a common procedure involving: place conditioning (0.3 or 1 mg/kg heroin or 20 mg/kg cocaine; ×4 sessions), extinction (vehicle × 4 sessions), and reconditioning (0 or 1 mg/kg heroin or 20 mg/kg cocaine; ×1 session). Systemic naloxone injections (0, 1 and 3 mg/kg) or bilateral intra-ventral tegmental area (VTA) naloxone methiodide infusions (2 nmol in 0.5 μl × side) were administered at different times following reconditioning. Post-reconditioning administration of naloxone dose-dependently blocked, attenuated and had no effect on reacquisition of heroin CPP when administered immediately, 1 h and 6 h after reconditioning, respectively. The highest dose of naloxone also blocked reacquisition of cocaine CPP, and did not produce a conditioned place aversion in heroin-naïve and heroin pre-treated animals. Post-reconditioning infusions in the VTA, but not in adjacent structures, blocked reacquisition of heroin CPP when administered immediately, but not 6 h, after reconditioning. These data suggest that reacquisition of drug-cues associations involves a memory consolidation process sensitive to manipulations of the endogenous opioid system, and indicate that opioid receptors in the VTA may be critically involved in the re-emergence of drug seeking behavior.     

Corvid caching: Insights from a cognitive model

Caching and recovery of food by corvids is well-studied, but some ambiguous results remain. To help clarify these, we built a computational cognitive model. It is inspired by similar models built for humans, and it assumes that memory strength depends on frequency and recency of use. We compared our model's behavior to that of real birds in previously published experiments. Our model successfully replicated the outcomes of two experiments on recovery behavior and two experiments on cache site choice. Our "virtual birds" reproduced declines in recovery accuracy across sessions, revisits to previously emptied cache sites, a lack of correlation between caching and recovery order, and a preference for caching in safe locations. The model also produced two new explanations. First, that Clark's nutcrackers may become less accurate as recovery progresses not because of differential memory for different cache sites, as was once assumed, but because of chance effects. And second, that Western scrub jays may choose their cache sites not on the basis of negative recovery experiences only, as was previously thought, but on the basis of positive recovery experiences instead. Alternatively, both "punishment" and "reward" may be playing a role. We conclude with a set of new insights, a testable prediction, and directions for future work.     

Rhesus monkeys (Macaca mulatta) demonstrate robust memory for what and where,but not when,in an open-field test of memory

We adapted a paradigm developed by Clayton and Dickinson (1998), who demonstrated memory for what, where, and when in scrub jays, for use with rhesus monkeys. In the study phase of each trial, monkeys found a preferred and a less-preferred food reward in a trial-unique array of three locations in a large room. After 1 h, monkeys returned to the test room, where they found foods placed as during study. Twenty-five hours after the study phase monkeys again searched the room, but now the preferred food was replaced with a distasteful food remnant, while the less-preferred food was still present. Although monkeys remembered the locations of the foods for up to 25 h, they did not learn that the preferred food was available after the short, but not after the long delay. Thus, monkeys demonstrated long-term memory for the type and location of food but failed to demonstrate sensitivity to when they acquired that knowledge.     

Effects of acute stress and GluN2B-containing NMDA receptor antagonism on object and object–place recognition memory

The mechanisms underlying the complex effects of acute stress on memory are incompletely understood. Previous work suggests that the activation of N-methyl-d-aspartate (NMDA) receptors specifically containing GluN2B subunits may underlie the disruptions in spatial memory retrieval caused by acute stress (Wong et al., 2007 PNAS 104:11471). The present experiments were designed to assess whether a similar mechanism is involved in recognition memory. Recognition memory retrieval was assessed in Sprague–Dawley rats using an object recognition test and an object–place recognition test, both of which rely on patterns of spontaneous exploration. Exposure to acute stress for 30 min immediately before the test phase of either test disrupted memory retrieval. Administration of the GluN2B-selective antagonist Ro25-6981 (6 mg/kg; i.p.) enhanced memory in the object recognition test regardless of whether animals were exposed to acute stress. In the object–place test, Ro25-6981 had no effect on memory retrieval in the absence of stress but promoted memory following acute stress. These data highlight the specific contributions made by GluN2B-containing NMDA receptors to recognition memory for different types of stimuli.     

Younger apes and human children plan their moves in a maze task

Planning defined as the predetermination of a sequence of actions towards some goal is crucial for complex problem solving. To shed light on the evolution of executive functions, we investigated the ontogenetic and phylogenetic origins of planning. Therefore, we presented all four great apes species (N = 12) as well as 4- and 5-year-old human preschoolers (N = 24) with a vertical maze task. To gain a reward placed on the uppermost level of the maze, subjects had to move the reward to the bottom through open gaps situated at each level of the maze. In total, there were ten gaps located over three of the maze’s levels, and free passage through these gaps could be flexibly blocked using multiple traps. Due to the decision tree design of the maze, the subjects had to plan their actions depending on the trap configuration up to two steps ahead to successfully retrieve the reward. We found that (1) our measure of planning was negatively correlated with age in nonhuman apes, (2) younger apes as well as 5-year-old children planned their moves up to two steps ahead whereas 4-year-olds were limited to plan one step ahead, and (3) similar performance but different underlying limitations between apes and children. Namely, while all species of nonhuman apes were limited by a lack of motor control, human children exhibited a shortage in shifting their attention across a sequence of subgoals.     

Effects of an activity-based anorexia procedure on within-session changes in nose-poke responding

This study tested the effects of an activity-based anorexia (ABA) procedure on within-session changes in responding. In the ABA group (N = 8), rats were given a 60-min feeding session and allowed to run in a running wheel for the remainder of each day. During the daily 60-min feeding session, each nose-poke response was reinforced by a food pellet. In the control group (N = 8), rats experienced the same procedure except that the wheel was locked and thus rats could not run. The experiment lasted for 6 days. Rats in the ABA group consumed less and lost more body weight than those in the control group. Within-session decreases in nose-poke responding were steeper for ABA than control rats. In addition, response rates were well described as linear functions of the cumulative number of reinforcers in both groups (r²s > .96). The regression lines for the ABA group had steeper slopes and smaller x-axis intercepts than those for the control group. However, the y-axis intercepts of the regression lines were similar for the two groups. These effects were different from the effects of taste-aversion learning induced by post-session wheel running (Aoyama, 2007), suggesting a different mechanism in each preparation.     

Central-place foraging by Rattus norvegicus on a radial maze

We studied central-place foraging in rats (Rattus norvegicus) by placing food items that varied in size and weight at the ends of a 4-arm radial maze. In Experiments 1-3, rats increasingly tended to carry food to the center of the maze as the size of those items increased. Very large food items often were hoarded in the center. Rats consumed food faster on the arms than in the center, and rats traveled faster when carrying food than when not. Blocking arm entrances increased travel time between the center and the arms and decreased food carrying at every item weight except the largest. In Experiments 4-6, important conditions that influence the degree of food-carrying behavior were discovered; these were the intersection of maze arms, the presence of a conspecific, and the use of open vs. closed maze arms.     

Strategic retrieval processing and the impact of knowing when a memory was first created

Retrieval orientation refers to a process where participants strategically alter how a memory cue is processed in response to different task demands. In the present study we explored whether retrieval orientation is influenced by knowing when an old stimulus was first encoded. Participants completed separate remember/know test blocks for old items from a recent delay (40 min) and old items from a remote delay (48 h). Manipulations at encoding ensured that performance levels were matched between these two blocks, thus avoiding confounds with differences in retrieval effort. Importantly, a third test block comprised old items from both delays randomly intermixed. As the nature of the old items varies unpredictably in the mixed block, it should not be possibly to adopt a specific retrieval orientation and the mixed block therefore acts as a control condition. Participants saw the words “mixed,” “recent” or “remote” prior to each test block. Comparing ERPs from the recent and remote blocks permitted an investigation of whether participants alter their retrieval orientation in response to the specific length of the retention interval. Comparing ERPs from the pure (recent and remote) test blocks to ERPs from the mixed block permitted an investigation of whether delay information per se led to differences in retrieval strategy. Analysis of the ERP data found no differences between the recent and remote blocks. However, ERPs from these pure blocks were significantly less positive than ERPs from the mixed block from 200 ms towards the end of the epoch. The findings suggest that the delay information was useful in a general sense and encouraged retrieval strategies distinct from those engaged in the mixed block. We speculate that such strategies might relate to whether or not the retrieval search is specific and constrained and/or whether processes that serve to reinstate the original encoding context are engaged.     

Increased stress-induced intra-hippocampus corticosterone rise associated with memory impairments in middle-aged mice

The present study investigates the relationships between hippocampal corticosterone concentrations and memory retrieval performance in stress and non-stress conditions, in both young (6 month-old) and middle-aged (16 month-old) mice. For this purpose, the time-course evolution of stress-induced corticosterone rise in the dorsal hippocampus (dHPC) was investigated in both young and middle-aged mice. In parallel, the evolution of memory retrieval patterns was assessed using a contextual serial discrimination task (CSD). Finally, metyrapone (corticosterone synthesis inhibitor) was administered in order to evaluate the stress-induced impact of corticosterone rise on contextual memory retrieval in middle-aged animals.Results showed that: (i) non-stressed middle-aged mice exhibited a memory retrieval pattern opposite to that of non-stressed young animals, but similar to that of stressed young mice; (ii) the impact of stress on memory performance was transient (90 min) in young, as compared to middle-aged mice (120 min); (iii) dHPC basal (non-stress) corticosterone level was significantly increased by ageing; (iv) acute stress induced a rapid (15 min) and transient (90 min) dHPC corticosterone rise in young mice, while exhibiting greater magnitude and duration (120 min) in middle-aged animals; and (v) both the stress-induced endocrinal and memory effects were blocked by metyrapone in young and middle-aged mice.Finally, to our knowledge, the present work is the first study to directly measure the corticosterone rise in the hippocampus following exposure to stress and to directly correlate the corticosterone changes in the hippocampus with memory performance in both young and middle-aged mice.