Forward and reverse hippocampal place-cell sequences during ripples Kamran Diba & Gyorgy Buzsaki

1. Forward and reverse hippocampal place-cell sequences during ripples Kamran Diba & Gyorgy Buzsaki

2. Hippocampal spatial map Sequences of cues are related into spatial episodes Temporal sequences are observed on several timescales: - as animals run through sequences of place-tuned fields. - at the timescale of hippocampal theta oscillations. - at the timescale of sharp-wave ripples. Eichenbaum et al., 1999

4. Illustration of place-field sequence “template”. Each neuron’s place-field is shown in a different color.

5. Member of TCD External Advisory and Scientific Board What happens during the sharp wave ripples?

6. Back and forth movement on a linear track for a water reward. Each neuron’s firing was tuned to a particular location along the track, which was stable from lap to lap The neurons fired in the forward temporal order during immobility prior to the run During immobility following the run, the same neurons fired again, but in the reverse temporal order

7. A sample event, depicting the first spikes from 5 different neurons. 4 example shuffled surrogate events, for which cell identities were shuffled across spikes.

8. 36% of all events were significantly forward correlated and 19% were significantly reverse correlated, in excess of the number expected by chance. Both preplay and replay events were correlated with sharpwave ripples, whichwere detected by filtering and thresholding the CA1 local field power in the 100–300-Hz (ripple) band.

9. Pre-play and replay sequences occur in both CA1 and CA3 regions.

10. Cross-correlograms (CCGs) of forward (preplay) and reverse (replay) events with CA1 sharp-wave ripple events. Both preplay and replay events were correlated with sharp wave ripples, which were detected by filtering and thresholding the CA1 local field power in the 100–300-Hz (ripple) band.

11. Do the ripple-associated neuronal sequences contain information about the distances between place fields on the track? (b) Temporal offsets between spikes of neuron pairs during significant forward (+) and reverse (o) events were correlated with distance representations between place-field peaks on the track. (c) Temporal offsets of cell pairs were related between track running (‘theta-scale time compression’) and forward (preplay) and reverse (replay) events.

12. Illustration of place-field sequence “template” and examples of forward and reverse replay sequences. Each neuron’s place-field is shown in a different color.

13. Preplay events may have a role in ‘planning’ upcoming trajectories. Similar mechanism most probably underlines the phenomenon of ‘splitter cells‘.

14. Neuroscience journals are quite hungry for well done papers

15. Bidirectional place cells cannot account for the forward or reverse sequences. Bidirectional place cells cannot account for the forward or reverse sequences. Top panel: histograms show rank-order correlations of the immobility sequences, and an equal number of shuffled surrogate events, to the place-field run sequence template, calculated when considering only events for which ? 4 unidirectional place-cells fired. A place-cell was considered unidirectional if its peak firing rate was ? 4 times (and ? 5 Hz) in one trajectory. Bottom panel: we correlated all significant events to templates created by the same neurons, but in the opposite trajectory regardless of peak firing rate (i.e. with no lower threshold—therefore even a few spikes could define the template). These histograms show that bidirectional cells do not explain the forward pre-play and reverse replay we observed.

16. Place field proximity cannot account for the forward or reverse sequences. Histograms show rank-order correlations, considering only events for which ≥ 4 neurons fired ≥ 10 cm outside of the boundaries of their place-fields (defined by 95 percent of the peak firing).

17. A hypothetical place-field model may account for sequences observed during both preplay and replay. Inputs for three neurons are indicated in color. A global spiking threshold is shown with a dashed line. On the track, this threshold is theta-modulated. On the platforms, during immobility, a transient decrease in the global threshold causes cells to fire outside of their classical place-fields.

18. Hebb: Neurons that fire together wire together Repeated event A A B B

19. Subicular sharp wave ripples – part of the game

20. Center for Molecular and Behavioral Neurobiology, Rutgers University, 197 University Ave, Newark, NJ 07102, E-mails: diba@.rutgers.edu, buzsaki@axon.rutgers.edu, Telephone: (973)353-1080 ext. 3361, Fax:(973)353-1820.