Hippocampal pyramidal cells use temporal 1 as well as rate coding 2 to signal spatial aspects of the animal's environment or behaviour. The temporal code takes the form of a phase relationship to the concurrent cycle of the hippocampal EEG theta rhythm (Figure 1; 1). These two codes could each represent a different variable 3,4. However, this requires that rate and phase can vary independently, in contrast to recent suggestions 5,6 that they are tightly coupled: both reflecting the amplitude of the cell's input. Here we show that the time of firing and firing rate are dissociable and can represent two independent variables, viz, the animal's location within the place field and its speed of movement through the field, respectively. Independent encoding of location together with actions and stimuli occurring there may help to explain the dual roles of the hippocampus in spatial and episodic memory 7 8 or a more general role in relational/declarative memory9,10.A cell must fire to manifest either a temporal or rate code. Place cells are hippocampal pyramidal cells that increase their firing rate in a particular portion of the environment 2,11 (the 'place field', see Fig1b). As such, they provide a coarse rate code for the animal's location within which a temporal code provides additional information1,12,13. In addition we propose that the rate of firing within the field can vary to encode for other information without disrupting this temporal code.We recorded the firing of place cells and the EEG from the hippocampi of rats as they ran back and forth on a linear track for food reward at each end (see Figure 1a and Methods). During this behaviour, the EEG shows the prominent theta oscillation and each place cell fires in a specific region of the track (Figure 1b). The cell's bursting rate through the field (Figure 1c) is slightly higher than the concurrent EEG theta frequency so that the average phase of firing moves earlier on each theta wave as the animal progresses through the field (Figure 1d). The phase of firing correlates with spatial variables such as the animal's position on the track or within the field (Fig. 1d), and also with non-spatial variables such as the time since entry into the field (Fig. 1e) or instantaneous firing rate (Figure 1f), but in general the correlation with position is stronger than with either ( Figure 1g; see also 1,5,6,12). Some process must align the phase of each spike relative to the concurrent theta wave so that the phase codes for location despite the different speeds of each run through the field.Correspondence and requests for material should be addressed to J.O'K (j.okeefe@ucl.ac.uk). * Present address: Department of Anatomy, University of Bristol Supplementary Information accompanies the paper on Nature's website (http://www.nature.com). Competing interests statementThe authors declare that they have no competing financial interests. Must the phase and rate codes always co-vary with each other or is it possible for them to dissociate? Harris et al 5 reported an ove...

The hippocampus is thought to be involved in episodic memory formation by reactivating traces of waking experience during sleep. Indeed, the joint firing of spatially tuned pyramidal cells encoding nearby places recur during sleep. We found that the sleep cofiring of rat CA1 pyramidal cells encoding similar places increased relative to the sleep session before exploration. This cofiring increase depended on the number of times that cells fired together with short latencies (<50 ms) during exploration, and was strongest between cells representing the most visited places. This is indicative of a Hebbian learning rule in which changes in firing associations between cells are determined by the number of waking coincident firing events. In contrast, cells encoding different locations reduced their cofiring in proportion to the number of times that they fired independently. Together these data indicate that reactivated patterns are shaped by both positive and negative changes in cofiring, which are determined by recent behavior.

Temporal coding is a means of representing information by the time, as opposed to the rate, at which neurons fire. Evidence of temporal coding in the hippocampus comes from place cells, whose spike times relative to theta oscillations reflect a rat's position while running along stereotyped trajectories. This arises from the backwards shift in cell firing relative to local theta oscillations (phase precession). Here we demonstrate phase precession during place-field crossings in an open-field foraging task. This produced spike sequences in each theta cycle that disambiguate the rat's trajectory through two-dimensional space and can be used to predict movement direction. Furthermore, position and movement direction were maximally predicted from firing in the early and late portions of the theta cycle, respectively. This represents the first direct evidence of a combined representation of position, trajectory and heading in the hippocampus, organized on a fine temporal scale by theta oscillations.

Hippocampal place cells that fire together within the same cycle of theta oscillations represent the sequence of positions (movement trajectory) that a rat traverses on a linear track. Furthermore, it has been suggested that the encoding of these and other types of temporal memory sequences is organized by gamma oscillations nested within theta oscillations. Here, we examined whether gamma-related firing of place cells permits such discrete temporal coding. We found that gamma-modulated CA1 pyramidal cells separated into two classes on the basis of gamma firing phases during waking theta periods. These groups also differed in terms of their spike waveforms, firing rates, and burst firing tendency. During gamma oscillations one group's firing became restricted to theta phases associated with the highest gamma power. Consequently, on the linear track, cells in this group often failed to fire early in theta-phase precession (as the rat entered the place field) if gamma oscillations were present. The second group fired throughout the theta cycle during gamma oscillations, and maintained gamma-modulated firing at different stages of theta-phase precession. Our results suggest that the two different pyramidal cell classes may support different types of population codes within a theta cycle: one in which spike sequences representing movement trajectories occur across subsequent gamma cycles nested within each theta cycle, and another in which firing in synchronized gamma discharges without temporal sequences encode a representation of location. We propose that gamma oscillations during theta-phase precession organize the mnemonic recall of population patterns representing places and movement paths.