This Week in The Journal

The critical role of the hippocampus in episodic memory has long been recognized. In particular, the hippocampus is thought to encode spatial, temporal, and semantic relationships among objects and events (Eichenbaum and Cohen, 2014, Neuron 83:764). Numerous human and rodent studies have provided support for this hypothesis. First, the discovery of place cells, which exhibit changes in firing rate as animals move through an environment, provided evidence that the rodent hippocampus represents spatial sequences. More recently, cells that appear to encode the passage of time have been identified. Now Allen et al. present evidence that hippocampal neurons encode temporal relationships between nonspatial stimuli. Rats were trained to recognize a sequence of five odors, after which they had to determine whether odors were presented in or out of order to earn a reward. Neuronal activity was recorded in CA1 as rats performed this task. The firing rate of 26% of recorded neurons (many more than would be expected by chance) differed depending on whether the odor being sniffed was in the learned sequence. Some neurons responded when the present odor was in the learned sequence— regardless of the odor’s identity—and others responded whenever an odor was experienced out of order. Some neurons responded only when a particular odor was presented in the correct position, and still others responded only when a particular odor was presented out of order. Finally, some neurons responded when any wrong odor was presented at a particular temporal position. Overall, the analyses suggested that the firing of individual neurons contained sufficient information to distinguish whether an odor was in or out of sequence, and that neuronal ensemble activity reflected whether items were in the learned sequence on a trial-bytrial basis. In these experiments, the location and overt behavior of rats were unchanged across trials, minimizing the likelihood that differences in neuronal firing were attributable to such confounds. Moreover, the proportion of cells that showed sequence-dependent changes in firing rate was correlated with accuracy on the task. Therefore, the results strongly suggest that hippocampal neurons encode temporal relationships between events—a central feature of episodic memories— and that this information is used to guide behavior.