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Theta sequences are essential for internally generated hippocampal firing fields

Abstract

Sensory cue inputs and memory-related internal brain activities govern the firing of hippocampal neurons, but which specific firing patterns are induced by either of the two processes remains unclear. We found that sensory cues guided the firing of neurons in rats on a timescale of seconds and supported the formation of spatial firing fields. Independently of the sensory inputs, the memory-related network activity coordinated the firing of neurons not only on a second-long timescale, but also on a millisecond-long timescale, and was dependent on medial septum inputs. We propose a network mechanism that might coordinate this internally generated firing. Overall, we suggest that two independent mechanisms support the formation of spatial firing fields in hippocampus, but only the internally organized system supports short-timescale sequential firing and episodic memory.

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Figure 1: The effects of muscimol injection on theta rhythm and task performance.
Figure 2: The effects of muscimol injection on the cell firing on the wheel (left) and in the maze (right).
Figure 3: Structure and firing patterns of the network model.
Figure 4: The effects of muscimol injection on the spatial firing pattern of neurons on a novel linear track.
Figure 5: The effects of muscimol injection on the spatial firing patterns of neurons on a large novel platform.
Figure 6: The effects of muscimol injection on the spatial firing pattern of neurons during repeated visits of a large novel platform.

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Acknowledgements

We thank W. Denk and G. Buzsáki for critical discussions and advice. We thank L. Abbott, M. Tsodyks and S. Druckmann for advice. We thank R. Egnor, A. Karpova, V. Jayaraman, A. Lee, J. Magee, N. Spruston, K. Svoboda, D. Hunt, A. Landragin and V. Bowman for their comments on early versions of the manuscript. We thank R. Wright for editorial help and mentorship. This work was supported by the Howard Hughes Medical Institute (E.P. and S.R.) and a Human Frontier Science Program Long-Term Fellowship (S.R.).

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Y.W. and E.P. design the study. Y.W., E.P., A.L. and B.L. analyzed the data. S.R. built the model. All of the authors discussed the data analysis and the model and commented on the manuscript.

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Correspondence to Eva Pastalkova.

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Wang, Y., Romani, S., Lustig, B. et al. Theta sequences are essential for internally generated hippocampal firing fields. Nat Neurosci 18, 282–288 (2015). https://doi.org/10.1038/nn.3904

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