The firing rate of hippocampal CA1 place cells is modulated with a circadian period.

The accurate recall of an event is usually dependent on a memory trace that encodes three pieces of information; what happened, when the event happened, and where. The established phenomenology of hippocampal CA1 pyramidal neurons could reflect mechanisms via which some of this information (where and what) is encoded; but so far there has been little evidence for a mechanism by which these cells might represent "when." It was therefore of interest to examine the activity of CA1 neurons over a substantial temporal duration. Forty-eight CA1 neurons were recorded once an hour during long (24-48 h) exposures to a single, stable environment where minimal time-of-day cues were available. Only data from the first 25 h of recording was analyzed quantitatively. We found that the mean ensemble firing rate of these cells changed predictably such that it was closely correlated (r = 0.707) to a reference sine wave with a 25-h period and a positive peak at recording start. This relationship was not explained by changes in the animal's running speed or amount of the recording environment covered in each recording session. When data were referenced to the onset or offset of the normal light-on period, the correlation with the sinusoid was abolished. At an individual cell level, the majority of neurons (n = 31) had significant correlations (P < 0.05) with the reference sine. We conclude that the firing rate of a large proportion of cells in area CA1 of the hippocampus are modulated over a circadian period but that this modulation is not entrained to light. Rather, entry into the environment and the associated food availability appear to be the entraining factors. We hypothesize that these neurons may be part of the putative food-entrainable oscillator. Such a system could enable an animal to discriminate between spatial representations on a temporal dimension with reference to the time of food availability.