Evidence for remembering when events occurred in a rodent model of episodic memory.
ABSTRACT: The content of episodic memory consists of representations of unique past events. Episodic memories are grounded in a temporal framework (i.e., we remember when an event occurred). It has recently been argued that episodic-like memory in rats is qualitatively different from human episodic memory because, rather than remembering when an earlier past event occurred, rats used the cue of how long ago it occurred. We asked, therefore, whether rats remember the time of day at which they encountered a distinctive event, in addition to what occurred and where it happened. Rats were tested in the morning and afternoon, on separate days. A distinctive flavor (chocolate) was replenished at a daily-unique location at only one of these times. The interval between first and second daily opportunities to eat (study and test, respectively) was constant. Rats adjusted their revisits to the chocolate location at different times of day by using time of day rather than the cue of how long ago an event occurred. Two lines of evidence suggest that rats remembered the time at which the distinctive event occurred. First, under conditions in which the time of test (but not time of study) was novel, rats immediately transferred their knowledge of the chocolate contingency to the new test time. Second, under conditions in which predictions for study and test times were put in conflict, rats again used study time. Our results suggest that, at the time of memory assessment, rats remember when a recent episode occurred, similar to human episodic memory.
Project description:Source memory is a representation of the origin (source) of information. When source information is bound together, it makes a memory episodic, allowing us to differentiate one event from another. Here, we asked whether rats remember the source of encoded information. Rats foraged for distinctive flavors of food that replenished (or failed to replenish) at its recently encountered location according to a source-information rule. To predict replenishment, rats needed to remember where they had encountered a preferred food type (chocolate) with self-generated (walking along a runway encountering chocolate) or experimenter-generated (placement of the rat at the chocolate site by an experimenter) cues. Three lines of evidence implicate the presence of source memory. First, rats selectively adjusted revisits to the chocolate location based on source information, under conditions in which familiarity of events could not produce successful performance. Second, source memory was dissociated from location memory by different decay rates. Third, temporary inactivation of the CA3 region of the hippocampus with lidocaine selectively eliminated source memory, suggesting that source memory is dependent upon an intact hippocampus. Development of an animal model of source memory may be valuable to probe the biological underpinnings of memory disorders marked by impairments in source memory.
Project description:Vivid episodic memories in people have been characterized as the replay of unique events in sequential order [1-3]. Animal models of episodic memory have successfully documented episodic memory of a single event (e.g., [4-8]). However, a fundamental feature of episodic memory in people is that it involves multiple events, and notably, episodic memory impairments in human diseases are not limited to a single event. Critically, it is not known whether animals remember many unique events using episodic memory. Here, we show that rats remember many unique events and the contexts in which the events occurred using episodic memory. We used an olfactory memory assessment in which new (but not old) odors were rewarded using 32 items. Rats were presented with 16 odors in one context and the same odors in a second context. To attain high accuracy, the rats needed to remember item in context because each odor was rewarded as a new item in each context. The demands on item-in-context memory were varied by assessing memory with 2, 3, 5, or 15 unpredictable transitions between contexts, and item-in-context memory survived a 45 min retention interval challenge. When the memory of item in context was put in conflict with non-episodic familiarity cues, rats relied on item in context using episodic memory. Our findings suggest that rats remember multiple unique events and the contexts in which these events occurred using episodic memory and support the view that rats may be used to model fundamental aspects of human cognition.
Project description:People remember an event as a coherent scene. Memory of such an episode is thought to reflect binding of a fully integrated representation, rather than memory of unconnected features. However, it is not known whether rodents form bound representations. Here we show that rats remember episodes as bound representations. Rats were presented with multiple features of unique episodes at memory encoding: what (food flavor), where (maze location), source (self-generated food seeking—running to the food site—or experimenter-generated food seeking—placement by the experimenter at the food site), and context (spatial cues in the room where the event occurred). After a delay, the trial continued with a memory assessment in which one flavor replenished at the self-generated—but not at experimenter-generated—locations. We presented rats with multiple overlapping features, in rapid succession, to ensure that successful memory retrieval required them to disambiguate multiple study episodes (using two rooms). We found that binding is resistant to interference from highly similar episodes and survives long retention intervals (?1 week). Our results suggest that multiple episodic memories are each structured as bound representations, which suggests that nonhumans represent episodic memories using a structure similar to that of people. This finding enhances the translational potential for utilizing animal models of episodic memory to explore the biological mechanisms of memory and validate therapeutic approaches for treating disorders of memory.
Project description:A fundamental aspect of episodic memory is that retrieval of information can occur when encoding is incidental and memory assessment is unexpected. These features are difficult to model in animals because behavioral training likely gives rise to well-learned expectations about the sequence of events. Thus, the possibility remains that animals may solve an episodic memory test by using well-learned semantic rules without remembering the episode at memory assessment. Here we show that rats can answer an unexpected question after incidental encoding in a hippocampal-dependent manner, consistent with the use of episodic memory. Rats were initially trained to report about a recent event (food versus no food) and separately searched for food where there was no expectation of being asked about the presence of food. To test episodic memory, we gave rats the opportunity to incidentally encode the presence or absence of food and unexpectedly asked them to report about the recent event. Temporary inactivation of the CA3 region of the hippocampus with bilateral infusions of lidocaine selectively eliminated the ability of rats to answer the unexpected, but not the expected, question. Our studies suggest that rats remember an earlier episode after incidental encoding based upon hippocampal-dependent episodic memory.
Project description:Vivid episodic memories in people have been characterized as the replay of multiple unique events in sequential order [1-3]. The hippocampus plays a critical role in episodic memories in both people and rodents [2, 4-6]. Although rats remember multiple unique episodes [7, 8], it is currently unknown if animals "replay" episodic memories. Therefore, we developed an animal model of episodic memory replay. Here, we show that rats can remember a trial-unique stream of multiple episodes and the order in which these events occurred by engaging hippocampal-dependent episodic memory replay. We document that rats rely on episodic memory replay to remember the order of events rather than relying on non-episodic memories. Replay of episodic memories survives a long retention-interval challenge and interference from the memory of other events, which documents that replay is part of long-term episodic memory. The chemogenetic activating drug clozapine N-oxide (CNO), but not vehicle, reversibly impairs episodic memory replay in rats previously injected bilaterally in the hippocampus with a recombinant viral vector containing an inhibitory designer receptor exclusively activated by a designer drug (DREADD; AAV8-hSyn-hM4Di-mCherry). By contrast, two non-episodic memory assessments are unaffected by CNO, showing selectivity of this hippocampal-dependent impairment. Our approach provides an animal model of episodic memory replay, a process by which the rat searches its representations in episodic memory in sequential order to find information. Our findings using rats suggest that the ability to replay a stream of episodic memories is quite old in the evolutionary timescale.
Project description:To examine episodic memory in rats, we trained rats to perform two tasks and tested them for memory of past self-behavior without making them expect to be asked about the memory later when encoding. One of the trained tasks was a delayed matching-to-position task in which the rats were required to remember the location of a presented lever. The other was a tone discrimination task in which the rats were required to discriminate between two pure tones. After learning both tasks, the rats were unexpectedly asked the location of the pressed lever after responding to the cue tone in probe trials during test sessions. The rats demonstrated a response bias that suggests that they have the ability to retrospectively recollect their self-behavior, i.e., episodic memory. We next made excitotoxic lesions in the retrosplenial cortex (RSC) and investigated the effects of the lesions on the unexpected recollection. In the rats with lesions of the RSC, the response bias disappeared. This suggests that the RSC has a role in retrospectively answering unexpected questions about self-behavior.
Project description:Source memory represents the origin (source) of information. Recently, we proposed that rats (Rattus norvegicus) remember the source of information. However, an alternative to source memory is the possibility that rats selectively encoded some, but not all, information rather than retrieving an episodic memory. We directly tested this 'encoding failure' hypothesis. Here, we show that rats remember the source of information, under conditions that cannot be attributed to encoding failure. Moreover, source memory lasted at least seven days but was no longer present 14 days after studying. Our findings suggest that long-lasting source memory may be modelled in non-humans. Our model should facilitate attempts to elucidate the biological underpinnings of source memory impairments in human memory disorders such as Alzheimer's disease.
Project description:A number of studies have provided evidence that animals, including rats, remember past episodes. However, few experiments have addressed episodic-like memory from a social perspective. In the present study, we evaluated Wistar rats in the WWWhen/ELM task as single setups and in dyads, applying a long retention interval. We also investigated behaviors that could subserve the emergence of this type of memory. We found that only rats tested in the social setting were able to recollect an integrated episodic-like memory that lasted 24 h. Additionally, rats in dyads presented higher levels of exploration during the task. When exposed to the testing environment, the dyads exhibited affiliative behavior toward each other and presented fewer anxiety-like responses. Our findings indicate that the presence of a conspecific could act as a facilitating factor in memory evaluations based on spontaneous exploration of objects and provide empirical support for applying more naturalistic settings in investigations of episodic-like memory in rats.
Project description:Many recent comparative studies have addressed "episodic" memory in nonhuman animals, suggesting that birds, rodents, great apes, and others can remember their own behavior after at least a half-day delay. By contrast, despite numerous studies regarding long-term memory, few comparable studies have been conducted on short-term retention for own behavior. In the current study, we addressed the following question: Do chimpanzees remember what they have just done? Four chimpanzees performed matching-to-sample and visual search tasks on a routine basis and were occasionally (every four sessions) given a "recognition" test immediately after their response during visual search trials. Even though these test trials were given very rarely, all four chimpanzees chose the stimulus they selected in the visual search trials immediately before the test trial significantly more frequently than they chose the stimulus they selected in another distractor trial. Subsequent experiments ruled out the possibility that preferences for the specific stimuli accounted for the recognition test results. Thus, chimpanzees remembered their own behavior even within a short-term interval. This type of memory may involve the transfer of episodic information from working memory to long-term episodic-like memory (i.e., an episodic buffer).