A Sequence of events model of episodic memory shows parallels in rats and humans

Abstract

A critical feature of episodic memory is the ability to remember the order of events as they occurred in time, a capacity shared across species including humans, nonhuman primates, and rodents. Accumulating evidence suggests that this capacity depends on a network of structures including the hippocampus and the prefrontal cortex, but their respective contributions remain poorly understood. As addressing this important issue will require converging evidence from complementary investigative techniques, we developed a cross-species, nonspatial sequence memory task suitable for behavioral and neurophysiological studies in rodents and in humans. The task involves the repeated presentation of sequences of items (odors in rats and images in humans) and requires subjects to make a judgment as to whether each item is presented "in sequence" or "out of sequence." To shed light on the cognitive processes and sequence representations supporting performance, different types of "out of sequence" probe trials were used including: (i) repeating an item from earlier in the sequence (Repeats; e.g., ABAD), (ii) skipping ahead in the sequence (Skips; e.g., ABD), and (iii) inserting an item from a different sequence into the same ordinal position (Ordinal Transfers; e.g., A2CD). We found a remarkable similarity in the performance of rats and humans, particularly in the pattern of results across probe trial types. Thus, the results suggest that rats and humans not only remember the sequences of events, but also use similar underlying cognitive processes and mnemonic representations. This strong cross-species correspondence validates this task for use in future basic and clinical interdisciplinary studies aimed at examining the neural mechanisms underlying episodic memory. V C 2014 Wiley Periodicals, Inc.

Nonspatial sequence coding varies along the CA1 transverse axis

“…There were two types of OutSeq items in the dataset: Repeats, in which an earlier item was presented a second time in the sequence (e.g., ABADE), and Skips, in which an item was presented too early in the sequence (e.g., ABDDE, which skipped over item C). Although our previous work has revealed important differences in performance and neural activity on Repeats and Skips (Allen et al, 2014, this distinction was beyond the scope of the present analyses and not further discussed here. Note that OutSeq items could be presented in any sequence position except the first (i.e., sequences always began with odor A, though odor A could also be presented later in the sequence as a Repeat).…”

“…Similarly, although the low incidence of sequence cells precludes a thorough analysis of their distribution in each animal, the observation of a high proportion of sequence cells in section 2 was generally consistent across animals. Fourth, although we have previously examined potential strategies and cognitive representations supporting performance of this task in rodents and humans (see Allen et al, 2014Allen et al, , 2015, including item-item associations (e.g., "B is followed by C") or item-position associations (e.g., "C is the third item in the sequence"), the present study was not designed to link the use of a specific strategy with the distribution of sequence coding in CA1. This assessment would require new experiments in which neural activity is recorded while biasing the animals toward the use of distinct strategies using different versions of the task.…”

“…Ongoing studies focusing on quantifying sequence coding in these subregions, as well as identifying the distinct contribution of specific projections within this network of structures, will be needed to further address this important issue. dorsal CA1 as rats performed a nonspatial sequence memory task that shows strong behavioral parallels in rats and humans (Allen et al, 2014). A, Apparatus and behavioral procedures.…”

“…The task involves repeated presentations of sequences of odors in a single odor port and requires subjects to determine whether each item is presented in its correct sequence position ("in sequence," or InSeq; e.g., ABC…) or in the wrong sequence position ("out of sequence," or OutSeq; e.g., ABD…). Rats Neural activity was recorded in dorsal CA1 as rats performed a nonspatial sequence memory task that shows strong behavioral parallels in rats and humans (Allen et al, 2014). Neural activity was recorded in dorsal CA1 as rats performed a nonspatial sequence memory task that shows strong behavioral parallels in rats and humans (Allen et al, 2014).…”

“…Neural activity was recorded from the transverse axis of dorsal CA1 as rats performed a crossspecies, nonspatial sequence memory task recently developed in our laboratory (Allen et al, 2014Figs 1, 2). Experimental procedures were reported in detail previously and thus only summarized here.…”