Episodic-Like Memory for What-Where-Which Occasion is Selectively Impaired in the 3xTgAD Mouse Model of Alzheimer’s Disease

Episodic memory loss is a defining feature of early-stage Alzheimer’s disease (AD). A test of episodic-like memory for the rat, the What-Where-Which occasion task (WWWhich), requires the association of object, location, and contextual information to form an integrated memory for an event. The WWWhich task cannot be solved by use of non-episodic information such as object familiarity and is dependent on hippocampal integrity. Thus, it provides an ideal tool with which to test capacity for episodic-like memory in the 3xTg murine model for AD. As this model captures much of the human AD phenotype, we hypothesized that these mice would show a deficit in the WWWhich episodic-like memory task. To test the specificity of any episodic-like deficit, we also examined whether mice could perform components of the WWWhich task that do not require episodic-like memory. These included object (Novel Object Recognition), location (Object Location Task, What-Where task), and contextual (What-Which) memory, as well as another three-component task that can be solved without reliance on episodic recall (What-Where-When; WWWhen). The results demonstrate for the first time that control 129sv/c57bl6 mice could form WWWhich episodic-like memories, wherea, 3xTgAD mice at 6 months of age were impaired. Importantly, while 3xTgAD mice showed some deficit on spatial component tasks, they were unimpaired in the more complex WWWhen combination task (which includes a spatial component and is open to non-episodic solutions). These results strongly suggest that AD pathology centered on the hippocampal formation mediates a specific deficit for WWWhich episodic-like memory in the 3xTgAD model

Wild chacma baboons (Papio ursinus) remember single foraging episodes

This study was supported by grants from Zürcher Hochschulverein, Schweizerische Akademie für Naturwissenschaften, Stiftung Thyll-Dürr, and Stiftung Annemarie Schindler, to R.N.Understanding animal episodic-like memory is important for tracing the evolution of the human mind. However, our knowledge about the existence and nature of episodic-like memory in non-human primates is minimal. We observed the behaviour of a wild male chacma baboon faced with a trade-off between protecting his stationary group from aggressive extra-group males and foraging among five out-of-sight platforms. These contained high-priority food at a time of natural food shortage. In 10 morning and eight evening trials, the male spontaneously visited the platforms in five and four different sequences, respectively. In addition, he interrupted foraging sequences at virtually any point on eight occasions, returning to the group for up to 2 h. He then visited some or all of the remaining platforms and prevented revisits to already depleted ones, apparently based on his memory for the previous foraging episode about food value, location, and time. Efficient use of memory allowed him to keep minimal time absent from his group while keeping food intake high. These findings support the idea that episodic-like memory offers an all-purpose solution to a wide variety of problems that require flexible, quick, yet precise decisions in situations arising from competition for food and mates in wild primates.PostprintPeer reviewe

Chimpanzees (Pan troglodytes) Fail a What-Where-When Task but Find Rewards by Using a Location-Based Association Strategy

Recollecting the what-where-when of an episode, or episodic-like memory, has been established in corvids and rodents. In humans, a linkage between remembering the past and imagining the future has been recognised. While chimpanzees can plan for the future, their episodic-like memory has hardly been investigated. We tested chimpanzees (Pan troglodytes) with an adapted food-caching paradigm. They observed the baiting of two locations amongst four and chose one after a given delay (15 min, 1 h or 5 h). We used two combinations of food types, a preferred and a less preferred food that disappeared at different rates. The subjects had to base their choices on the time elapsed since baiting, and on their memory of which food was where. They could recover either their preferred food or the one that remained present. All animals failed to obtain the preferred or present foods above chance levels. They were like-wise unsuccessful at choosing baited cups above chance levels. The subjects, thus, failed to use any feature of the baiting events to guide their choices. Nonetheless, their choices were not random, but the result of a developed location-based association strategy. Choices in the second half of the study correlated with the rewards obtained at each location in the first half of the study, independent from the choices made for each location in the first half of the study. This simple location-based strategy yielded a fair amount of food. The animals' failure to remember the what-where-when in the presented set-up may be due to the complexity of the task, rather than an inability to form episodic-like memories, as they even failed to remember what was where after 15 minutes

Hippocampal-Dependent Spatial Memory in the Water Maze is Preserved in an Experimental Model of Temporal Lobe Epilepsy in Rats

Cognitive impairment is a major concern in temporal lobe epilepsy (TLE). While different experimental models have been used to characterize TLE-related cognitive deficits, little is known on whether a particular deficit is more associated with the underlying brain injuries than with the epileptic condition per se. Here, we look at the relationship between the pattern of brain damage and spatial memory deficits in two chronic models of TLE (lithium-pilocarpine, LIP and kainic acid, KA) from two different rat strains (Wistar and Sprague-Dawley) using the Morris water maze and the elevated plus maze in combination with MRI imaging and post-morten neuronal immunostaining. We found fundamental differences between LIP- and KA-treated epileptic rats regarding spatial memory deficits and anxiety. LIP-treated animals from both strains showed significant impairment in the acquisition and retention of spatial memory, and were unable to learn a cued version of the task. In contrast, KA-treated rats were differently affected. Sprague-Dawley KA-treated rats learned less efficiently than Wistar KA-treated animals, which performed similar to control rats in the acquisition and in a probe trial testing for spatial memory. Different anxiety levels and the extension of brain lesions affecting the hippocampus and the amydgala concur with spatial memory deficits observed in epileptic rats. Hence, our results suggest that hippocampal-dependent spatial memory is not necessarily affected in TLE and that comorbidity between spatial deficits and anxiety is more related with the underlying brain lesions than with the epileptic condition per se

Temporal context and conditional associative learning

<p>Abstract</p> <p>Background</p> <p>We investigated how temporal context affects the learning of arbitrary visuo-motor associations. Human observers viewed highly distinguishable, fractal objects and learned to choose for each object the one motor response (of four) that was rewarded. Some objects were consistently preceded by specific other objects, while other objects lacked this task-irrelevant but predictive context.</p> <p>Results</p> <p>The results of five experiments showed that predictive context consistently and significantly accelerated associative learning. A simple model of reinforcement learning, in which three successive objects informed response selection, reproduced our behavioral results.</p> <p>Conclusions</p> <p>Our results imply that not just the representation of a current event, but also the representations of past events, are reinforced during conditional associative learning. In addition, these findings are broadly consistent with the prediction of attractor network models of associative learning and their prophecy of a persistent representation of past objects.</p

Interhemispheric transfer of visuomotor conditional learning via the anterior corpus callosum of monkeys.

Two experiments examined interhemispheric transfer of learning across the anterior corpus callosum in monkeys (Macaca fascicularis). The animals learned a series of visuomotor conditional discrimination problems for food reward. Within each problem the animals were first trained using one hand to make the motor responses, and were then required to use the opposite hand in order to test for intermanual transfer of the initial learning. In Exp. 1, a group of animals with surgical section of the entire corpus callosum and anterior commissure showed a complete absence of intermanual transfer of learning. A second group, in which only the anterior commissure and the posterior part of the corpus callosum were sectioned, leaving the anterior corpus callosum intact, showed good intermanual transfer. Thus, intermanual transfer in the second group represented interhemispheric information transfer via the anterior portions of the corpus callosum. However, in Expt. 2, normal intermanual transfer was seen in a group of animals in which the anterior corpus callosum alone had been sectioned. We conclude that the anterior corpus callosum can mediate interhemispheric transfer of visuomotor conditional learning, but is not the only available route for such transfer in the present task

Reaching to a rewarded visual stimulus: interhemispheric conflict and hand use in monkeys with forebrain commissurotomy.

Monkeys (Macaca fascicularis) learned simultaneous visual discriminations for food reward. Two coloured patterns were presented one above the other and the monkey chose one by touching it with a hand. On some trials, conflicting information was presented to the two visual hemifields. For example, in the left hemifield the stimulus associated with reward was in the higher position and in the right hemifield the stimulus associated with reward was in the lower position. On some of these conflict trials the monkeys were required to use the left hand and on others the right. Normal monkeys, monkeys with section of the anterior commissure and the posterior corpus callosum, and monkeys with section of the anterior commissure and the whole of the corpus callosum performed this task. Our aim was to test the hypothesis that following forebrain commissurotomy, the response made by each hand would be predominantly influenced by the visual information put into the hemisphere contralateral to that hand. If this is true then choices in the conflict test should vary systematically with hand use. This hypothesis was not confirmed. We conclude that when a monkey reaches to a rewarded visual stimulus, information about the reward history of the stimulus is integrated between the hemispheres before influencing the motor control of the hand that reaches, either by a peripheral or a subcortical route.

Interhemispheric transfer of visual learning in monkeys with intact optic chiasm.

The purpose of the present experiments was to investigate the role of the forebrain commissures in interhemispheric visual transfer when both eyes are open and the optic chiasm is intact. Cynomolgus monkeys (Macaca fascicularis) learned a series of two-choice simultaneous visual discriminations. The visual stimuli were bipartite, with independently determined left and right halves. If such a stimulus is fixated centrally, the two halves fall into opposite visual hemifields. After 10 trials of acquisition of each discrimination, the same discriminanda were presented for a further 10 trials in which, within each stimulus, the positions of the halves were exchanged: the left half became the right and vice versa. The unoperated animals transferred well to the altered stimuli, making many fewer errors than they made in learning the originally presented discrimination. In contrast, monkeys with section of the posterior corpus callosum and the anterior commissure transferred poorly. These effects show that the forebrain commissures are important for the interhemispheric transfer and integration of visual information in animals with a normal, intact peripheral visual system