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Hippocampal theta sequences reflect current goals

Nature Neuroscience volume 18, pages 289–294 (2015)Cite this article

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Abstract

Hippocampal information processing is discretized by oscillations, and the ensemble activity of place cells is organized into temporal sequences bounded by theta cycles. Theta sequences represent time-compressed trajectories through space. Their forward-directed nature makes them an intuitive candidate mechanism for planning future trajectories, but their connection to goal-directed behavior remains unclear. As rats performed a value-guided decision-making task, the extent to which theta sequences projected ahead of the animal's current location varied on a moment-by-moment basis depending on the rat's goals. Look-ahead extended farther on journeys to distant goals than on journeys to more proximal goals and was predictive of the animal's destination. On arrival at goals, however, look-ahead was similar regardless of where the animal began its journey from. Together, these results provide evidence that hippocampal theta sequences contain information related to goals or intentions, pointing toward a potential spatial basis for planning.

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Figure 1: Behavioral task.
Figure 2: Theta sequences reflect future choices.
Figure 3: Look-ahead distance varied with the length of planned trajectories.
Figure 4: Look-ahead was constant on goal arrival.
Figure 5: Theta look-ahead predicted rats' current goals.
Figure 6: Place field size was modulated by trajectory type.
Figure 7: Look-ahead was modulated by goal location on single trials.

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Acknowledgements

The authors thank members of the Redish laboratory for discussion about this work. A.M.W. was supported by US National Institutes of Health grant T32-DA-07234 and a University of Minnesota Doctoral Dissertation Fellowship. A.D.R. was supported by US National Institutes of Health grant R01-MH-080318. This work was also supported by US National Institutes of Health grant R56-MH-080318.

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Authors and Affiliations

  1. Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota, USA

    Andrew M Wikenheiser

  2. Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota, USA

    A David Redish

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Contributions

A.M.W. and A.D.R. designed the experiments. A.M.W. collected the data. A.M.W. and A.D.R. analyzed the data. A.M.W. and A.D.R. wrote the manuscript.

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Correspondence to A David Redish.

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Integrated supplementary information

Supplementary Figure 1 Theta sequences

Rasters of place cell spiking are plotted for five example theta cycles. Cells are sorted on the y (space) axis according to the location of their place field center relative to the rat’s instantaneous location (positive numbers indicate space ahead of the rat). The LFP (unfiltered, and filtered from 6–10 hz) is plotted below each raster. In the 2D spatial plots, dots denote the place field center of each cell that was active during the theta cycle, and a black x indicates the rat’s position. In both plots, spikes are color coded to indicate the order in which cells became active.

Supplementary Figure 2 Theta look-ahead was consistent within subject, across space, and for different methods of identifying trajectories.

(a) Mean look ahead distance (±95% confidence interval) is plotted for individual rats on initiation of trajectories (left panel, cf. fig. 3 in the main text) and on completion of trajectories (right panel, cf. fig. 4 in the main text). (b) Look ahead distance was computed separately for one, two, and three segment trajectories beginning or ending at each of the three physical feeder locations. Patterns were similar in all cases. Error bars denote 95 % confidence intervals. (c) Using a more stringent running speed threshold for identifying trajectories (25 cm/s rather than 10 cm/s; see Methods) did not alter the pattern of theta sequence look ahead observed on trajectory departure or arrival at goal destinations. Error bars denote 95% confidence intervals.

Supplementary Figure 3 Alternative methods of computing theta look-ahead distance did not influence results.

Taking the theta look ahead distance as either (a) the distance between the rat’s current location and the place field center of the last spike to occur within each theta sequence, or (b) the distance between the rat’s current location and the place field center of the cell farthest in front of rats’ current location that was active in the cycle (regardless of when the cell fired in the theta cycle) produced similar patterns of results across trajectories.

Supplementary Figure 4 Place cell firing rates were similar across trajectories.

We computed the average firing rates of place cells separately for different trajectory types. Differences in rate across trajectories were not significant. The p values plotted in each figure are for sign tests.

Supplementary Figure 5 Properties of theta cycles.

(a) The period of theta cycles was not consistently related to theta look ahead distance. Shaded regions indicate the standard error of the mean. (b) The symmetry of theta cycles did not vary substantially across different values of theta look ahead distance. Shaded regions indicated the standard error of the mean. (c) We constructed histograms of ensemble place cell spiking across the theta cycle for different look ahead distances. A theta phase of 0 corresponds to the trough of the theta oscillation as recorded from the hippocampal fissure. Histograms are normalized within row to display the proportion of place cell spikes at different phases of theta. Spiking was generally concentrated in the same portion of the theta cycle at different values of look ahead distance, although a slight shift to later phases is evident for theta cycles where look ahead was farthest in front of the animal.

Supplementary Figure 6 Movement parameters did not account for differences in look-ahead on trajectory departure.

Histograms display running speed (a) and acceleration (b) for the theta sequences analyzed in fig. 3 of the main text. Because there were differences between the three trajectory types, we constructed surrogate theta look ahead data sets (matched to the data used to construct fig. 3; n = 20,269 theta cycles) assuming that speed (c), acceleration (d), or particular combinations of speed and acceleration (e) determined theta look ahead. No goal-dependent effects were detected in these bootstrapped data sets.

Supplementary Figure 7 Forward-directed theta representations are more common on longer trajectories.

We computed the proportion of theta sequence trajectory representations that ended in different regions of the track as animals traversed the first limb of trajectories. On trajectory initiation (left panel), the proportion of sequences that ended in the space between the rat’s start site and the next feeder on the maze (zonen) was highest during one segment trajectories and decreased on two and three segment trajectories. The proportion of sequences that ended in zonen+1 was lowest for one segment trajectories and greatest for three segment trials. The proportion of sequences that extended to the zone farthest from the departure site zonen+2/n−1 was specifically increased on three segment trajectories. In contrast, as rats traversed the final limb of trajectories on arrival at goal destinations (right panel), no trajectory-dependent differences in the proportions of sequences ending in particular spatial zones were detected. In both panels, error bars indicate the standard error of the mean across recording sessions.

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Wikenheiser, A., Redish, A. Hippocampal theta sequences reflect current goals. Nat Neurosci 18, 289–294 (2015). https://doi.org/10.1038/nn.3909

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