TECHNICAL COMMENTS: "Replay" of Hippocampal "Memories".

William E. Skaggs and Bruce L. McNaughton state, in the title of their report, that they found a "Replay of neuronal firing sequences in rat hippocampus during sleep following spatial experience" (1). On the basis of the evidence they present, we question that finding. Skaggs and McNaughton analyzed recordings from pairs of rat hippocampal neurons during a period of running on a closed track and a period of sleep immediately after. Each cell typically fires 'at a high rate when the animal enters a zone on the track called its "place field." When the fields of the two cells do not overlap, the cells fire in the order that the animal encounters their respective fields. During subsequent sleep, the same cells tend to fire nearly synchronous bursts. Skaggs and McNaughton state that the temporal order of activation of two cellsnot their "firing sequences" but their sequence in firing-is the same during track running and in the sleep period that follows. Skaggs and McNaughton do not base this statement on the observed firing of the cells, but rather on a novel "measure of temporal ordering" they call "temporal bias." This bias is computed from a crosscorrelogram of the spike trains of a pair of cells, and is therefore dependent on the detailed timings of both spike trains. During running, those spike trains are influenced in a complex way by the shape and arrangement of the two place fields, the running speed of the animal (which may be age-dependent), track geometry and its familiarity, ongoing theta activity, and the propensity of the animal to stop and receive a food reward [see the legend of figure 1 and note 11 in the report (I)]. Thus, although the temporal order in which the animal encounters place fields may affect bias, these other factors render it an unsuitable and unreliable indicator of temporal order of firing under most conditions. Furthermore, the algebraic sign of bias is neither a necessary nor sufficient condition for fixing the temporal order of firing of two cells. To give a simple example, consider the following three spike sequences