Hippocampus is required for paired associate memory with neither delay nor trial uniqueness

Abstract

Cued retrieval of memory is typically examined with delay when testing hippocampal functions, as in delayed matching-tosample tasks. Equally emphasized in the literature, on the other hand, is the hippocampal involvement in making arbitrary associations. Paired associate memory tasks are widely used for examining this function. However, the two variables (i.e., delay and paired association) were often mixed in paired associate tasks, and this makes it difficult to localize the cognitive source of deficits with hippocampal perturbation. Specifically, a few studies have recently shown that rats can learn arbitrary paired associations between certain locations and nonspatial items (e.g., object or flavor) and later can retrieve the paired location when cued by the item remotely. Such tasks involve both (1) delay between sampling the cue and retrieving the target location and (2) arbitrary association between the cueing object and its paired location. Here, we tested whether delay was necessary in a cued paired associate task by using a task in which no delay existed between object cueing and the choice of its paired associate. Moreover, fixed associative relationships between the cueing objects and their paired locations were repeatedly used, thus involving no trial-unique association. Nevertheless, inactivations of the dorsal hippocampus with muscimol severely disrupted retrieval of paired associates, whereas the same manipulations did not affect discriminating individual objects or locations. The results powerfully demonstrate that the hippocampus is inherently required for retrieving paired associations between objects and places, and that delay and trial uniqueness of the paired associates are not necessarily required.[Supplemental material is available for this article.]Animal models for testing episodic memory have been particularly useful for studying a selective contribution of the hippocampus and its neural mechanisms. One of the animal models in the literature involves teaching paired associative relationships between mnemonic items and then testing the retrieval of a learned item when cued by its paired associate (Bunsey and Eichenbaum 1993;Day et al. 2003;Kesner et al. 2005). Recently, Day et al. (2003) proposed an impressive rodent version of cued paired associate task, in which rats formed paired associate memory between a particular flavor and its paired associate location. Specifically, in the task, the rat should learn flavor-place paired association during spatial navigation in a sample phase. In the retrieval phase, the rat was cued with one of the flavors learned during the sample phase and was required to navigate to its paired associate place. Compared with other paired associate tasks (Cho and Kesner 1995; Bunsey and Eichenbaum 1996; Lee and Solivan 2008), animals must learn a trial-unique paired association in a single trial in this task. Furthermore, the rat was cued in the start box (thus, away from its original sampling location) during the test phase. Importantly, this feature of the tas...

Contextual behavior and neural circuits

“…Although one may predict that this task may have been solved easily by associating egocentric responses with cueing objects (which is not known to be hippocampal dependent), surprisingly, inactivation of the dorsal hippocampus with muscimol severely disrupted normal performance for two consecutive days. We confirmed that the rats used visual cues in the background by showing that rats were not able to do this task in the dark either with or without hippocampal inactivations (Yoon et al, 2012). We also showed that rats were able to perceptually discriminate the cueing objects in the dark (presumably using tactile information).…”

“…We tested recently whether those additional cognitive processes mentioned above were critical in testing hippocampal functions for contextual item–response selection by using a simpler paradigm (Yoon et al, 2012). In our task, the rat just ran along a straight track (thus with almost no requirement for spatial navigation) upon exiting a start box and encountered a toy object at the end of the track (Figure 8).…”

How does the hippocampal formation mediate memory for stimuli processed by the magnocellular and parvocellular visual pathways? Evidence from the comparison of schizophrenia and amnestic mild cognitive impairment (aMCI)

“…Interestingly, patients and controls performed similarly on the orientation discrimination task, suggesting a relative specificity of findings for memory processes, that is, the deficit cannot be explained by reduced sensory capacities leading to a failure to differentiate the orientation of the stimuli. Consistent with this finding, Yoon, Seo, Kim, and Lee (2011) demonstrated that pharmacological inactivation of the dorsal hippocampus in animal experiments disrupted paired associates learning, whereas it did not affect the discrimination of individual objects or locations.…”

The Critical Role of Sleep Spindles in Hippocampal-Dependent Memory: A Pharmacology Study

“…More specifically, we show that pharmacologically enhancing sleep spindles in healthy adults produces exceptional memory performance beyond that seen with sleep alone (placebo) or sleep with the comparison drug (SO). The hippocampus has previously been shown to particularly engage learning of associative elements (Davachi and Wagner, 2002; Yoon et al, 2012), and associative verbal learning has been correlated with sleep spindles (Gais et al, 2002; Schabus et al, 2004; Clemens et al, 2005; Schmidt et al, 2006). We, therefore, used an associative verbal learning task to test the prediction that sleep spindles play a critical role in hippocampal-dependent memory consolidation.…”