Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Entrained rhythmic activities of neuronal ensembles as perceptual memory of time interval


The ability to process temporal information is fundamental to sensory perception, cognitive processing and motor behaviour of all living organisms, from amoebae to humans1,2,3,4. Neural circuit mechanisms based on neuronal and synaptic properties have been shown to process temporal information over the range of tens of microseconds to hundreds of milliseconds5,6,7. How neural circuits process temporal information in the range of seconds to minutes is much less understood. Studies of working memory in monkeys and rats have shown that neurons in the prefrontal cortex8,9,10, the parietal cortex9,11 and the thalamus12 exhibit ramping activities that linearly correlate with the lapse of time until the end of a specific time interval of several seconds that the animal is trained to memorize. Many organisms can also memorize the time interval of rhythmic sensory stimuli in the timescale of seconds and can coordinate motor behaviour accordingly, for example, by keeping the rhythm after exposure to the beat of music. Here we report a form of rhythmic activity among specific neuronal ensembles in the zebrafish optic tectum, which retains the memory of the time interval (in the order of seconds) of repetitive sensory stimuli for a duration of up to 20 s. After repetitive visual conditioning stimulation (CS) of zebrafish larvae, we observed rhythmic post-CS activities among specific tectal neuronal ensembles, with a regular interval that closely matched the CS. Visuomotor behaviour of the zebrafish larvae also showed regular post-CS repetitions at the entrained time interval that correlated with rhythmic neuronal ensemble activities in the tectum. Thus, rhythmic activities among specific neuronal ensembles may act as an adjustable ‘metronome’ for time intervals in the order of seconds, and serve as a mechanism for the short-term perceptual memory of rhythmic sensory experience.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Visual-stimulation-evoked Ca 2+ transients in an ensemble of tectal neurons.
Figure 2: Repetitive conditioning stimulation induces post-CS rhythmic Ca 2+ transients.
Figure 3: Rhythmic activities of neuronal ensembles are stimulus-specific.
Figure 4: Repetitive visual CS induces post-CS rhythmic motor behaviour.


  1. Gibbon, J., Malapani, C., Dale, C. L. & Gallistel, C. R. Toward a neurobiology of temporal cognition: Advances and challenges. Curr. Opin. Neurobiol. 7, 170–184 (1997)

    CAS  Article  Google Scholar 

  2. Buhusi, C. V. & Meck, W. H. What makes us tick? Functional and neural mechanisms of interval timing. Nature Rev. Neurosci. 6, 755–765 (2005)

    CAS  Article  Google Scholar 

  3. Buonomano, D. V. The biology of time across different scales. Nature Chem. Biol. 3, 594–597 (2007)

    CAS  Article  Google Scholar 

  4. Saigusa, T., Tero, A., Nakagaki, T. & Kuramoto, Y. Amoebae anticipate periodic events. Phys. Rev. Lett. 100, 018101 (2008)

    ADS  Article  Google Scholar 

  5. Carr, C. E. Processing of temporal information in the brain. Annu. Rev. Neurosci. 16, 223–243 (1993)

    CAS  Article  Google Scholar 

  6. Buonomano, D. V. Timing of neural responses in cortical organotypic slices. Proc. Natl Acad. Sci. USA 100, 4897–4902 (2003)

    ADS  CAS  Article  Google Scholar 

  7. Buonomano, D. V. & Karmarkar, U. R. How do we tell time? Neuroscientist 8, 42–51 (2002)

    Article  Google Scholar 

  8. Rainer, G., Rao, S. C. & Miller, E. K. Prospective coding for objects in primate prefrontal cortex. J. Neurosci. 19, 5493–5505 (1999)

    CAS  Article  Google Scholar 

  9. Quintana, J. & Fuster, J. M. From perception to action: temporal integrative functions of prefrontal and parietal neurons. Cereb. Cortex 9, 213–221 (1999)

    CAS  Article  Google Scholar 

  10. Brody, C. D., Hernandez, A., Zainos, A. & Romo, R. Timing and neural encoding of somatosensory parametric working memory in macaque prefrontal cortex. Cereb. Cortex 13, 1196–1207 (2003)

    Article  Google Scholar 

  11. Leon, M. I. & Shadlen, M. N. Representation of time by neurons in the posterior parietal cortex of the macaque. Neuron 38, 317–327 (2003)

    CAS  Article  Google Scholar 

  12. Komura, Y. et al. Retrospective and prospective coding for predicted reward in the sensory thalamus. Nature 412, 546–549 (2001)

    ADS  CAS  Article  Google Scholar 

  13. Meek, J. Functional anatomy of the tectum mesencephali of the goldfish. An explorative analysis of the functional implications of the laminar structural organization of the tectum. Brain Res. 287, 247–297 (1983)

    CAS  Article  Google Scholar 

  14. Vanegas, H. & Ito, H. Morphological aspects of the teleostean visual system: a review. Brain Res. 287, 117–137 (1983)

    CAS  Article  Google Scholar 

  15. Denk, W., Strickler, J. H. & Webb, W. W. Two-photon laser scanning fluorescence microscopy. Science 248, 73–76 (1990)

    ADS  CAS  Article  Google Scholar 

  16. Stosiek, C., Garaschuk, O., Holthoff, K. & Konnerth, A. In vivo two-photon calcium imaging of neuronal networks. Proc. Natl Acad. Sci. USA 100, 7319–7324 (2003)

    ADS  CAS  Article  Google Scholar 

  17. Niell, C. M. & Smith, S. J. Functional imaging reveals rapid development of visual response properties in the zebrafish tectum. Neuron 45, 941–951 (2005)

    CAS  Article  Google Scholar 

  18. McLean, D. L., Fan, J., Higashijima, S., Hale, M. E. & Fetcho, J. R. A topographic map of recruitment in spinal cord. Nature 446, 71–75 (2007)

    ADS  CAS  Article  Google Scholar 

  19. Ramdya, P., Reiter, B. & Engert, F. Reverse correlation of rapid calcium signals in the zebrafish optic tectum in vivo . J. Neurosci. Methods 157, 230–237 (2006)

    CAS  Article  Google Scholar 

  20. Yaksi, E. & Friedrich, R. W. Reconstruction of firing rate changes across neuronal populations by temporally deconvolved Ca2+ imaging. Nature Methods 3, 377–383 (2006)

    CAS  Article  Google Scholar 

  21. Nakai, J., Ohkura, M. & Imoto, K. A high signal-to-noise Ca2+ probe composed of a single green fluorescent protein. Nature Biotechnol. 19, 137–141 (2001)

    CAS  Article  Google Scholar 

  22. Gahtan, E., Tanger, P. & Baier, H. Visual prey capture in larval zebrafish is controlled by identified reticulospinal neurons downstream of the tectum. J. Neurosci. 25, 9294–9303 (2005)

    CAS  Article  Google Scholar 

  23. Sato, T., Hamaoka, T., Aizawa, H., Hosoya, T. & Okamoto, H. Genetic single-cell mosaic analysis implicates ephrinB2 reverse signaling in projections from the posterior tectum to the hindbrain in zebrafish. J. Neurosci. 27, 5271–5279 (2007)

    CAS  Article  Google Scholar 

  24. Bullock, T. H., Hofmann, M. H., New, J. G. & Nahm, F. K. Dynamic properties of visual evoked potentials in the tectum of cartilaginous and bony fishes, with neuroethological implications. J. Exp. Zool. 256, 142–155 (1990)

    Article  Google Scholar 

  25. Bullock, T. H., Hofmann, M. H., Nahm, F. K., New, J. G. & Prechtl, J. C. Event-related potentials in the retina and optic tectum of fish. J. Neurophysiol. 64, 903–914 (1990)

    CAS  Article  Google Scholar 

  26. Bullock, T. H., Karamursel, S. & Hofmann, M. H. Interval-specific event related potentials to omitted stimuli in the electrosensory pathway in elasmobranchs: an elementary form of expectation. J. Comp. Physiol. [A] 172, 501–510 (1993)

    CAS  Article  Google Scholar 

  27. Bullock, T. H., Karamursel, S., Achimowicz, J. Z., McClune, M. C. & Basar-Eroglu, C. Dynamic properties of human visual evoked and omitted stimulus potentials. Electroencephalogr. Clin. Neurophysiol. 91, 42–53 (1994)

    CAS  Article  Google Scholar 

  28. Schwartz, G., Harris, R., Shrom, D. & Berry, M. J. Detection and prediction of periodic patterns by the retina. Nature Neurosci. 10, 552–554 (2007)

    CAS  Article  Google Scholar 

  29. Lister, J. A., Robertson, C. P., Lepage, T., Johnson, S. L. & Raible, D. W. nacre encodes a zebrafish microphthalmia-related protein that regulates neural-crest-derived pigment cell fate. Development 126, 3757–3767 (1999)

    CAS  PubMed  Google Scholar 

  30. O’Malley, D. M. et al. Optical physiology and locomotor behaviors of wild-type and nacre zebrafish. Methods Cell Biol. 76, 261–284 (2004)

    Article  Google Scholar 

  31. Westerfield, M. The Zebrafish Book; A Guide for the Laboratory Use of Zebrafish (Danio rerio) (Eugene, Univ. Oregon Press, 2000)

    Google Scholar 

  32. Brustein, E., Marandi, N., Kovalchuk, Y., Drapeau, P. & Konnerth, A. “In vivo” monitoring of neuronal network activity in zebrafish by two-photon Ca2+ imaging. Pflugers Arch. 446, 766–773 (2003)

    CAS  Article  Google Scholar 

  33. Brainard, D. H. The psychophysics toolbox. Spat. Vis. 10, 433–436 (1997)

    CAS  Article  Google Scholar 

  34. Pelli, D. G. The VideoToolbox software for visual psychophysics: transforming numbers into movies. Spat. Vis. 10, 437–442 (1997)

    CAS  Article  Google Scholar 

  35. Easter, S. S. & Nicola, G. N. The development of vision in the zebrafish (Danio rerio). Dev. Biol. 180, 646–663 (1996)

    CAS  Article  Google Scholar 

  36. Thévenaz, P., Ruttimann, U. E. & Unser, M. A pyramid approach to subpixel registration based on intensity. IEEE Trans. Image Process. 7, 27–41 (1998)

    ADS  Article  Google Scholar 

  37. Ritter, D. A., Bhatt, D. H. & Fetcho, J. R. In vivo imaging of zebrafish reveals differences in the spinal networks for escape and swimming movements. J. Neurosci. 21, 8956–8965 (2001)

    CAS  Article  Google Scholar 

  38. Burgess, H. A. & Granato, M. Modulation of locomotor activity in larval zebrafish during light adaptation. J. Exp. Biol. 210, 2526–2539 (2007)

    Article  Google Scholar 

Download references


We thank A. Kampff, F. Engert, Y. Fu and S. Smith for their help with two-photon microscopy, C. Niell for advice on the zebrafish preparation, N. Farchi, Y. Loewenstein, B. Hochner, G. de Polavieja and A. Noe for comments on the manuscript, and A. Arrenberg, B. Barak, V. Yoon, R. Chen and J. Sumbre for their technical help. This work was supported by the US National Institutes of Health.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Mu-ming Poo.

Supplementary information

Supplementary Information

This file contains Supplementary Methods and References, and Supplementary Figures 1-9 with Legends (PDF 2362 kb)

Supplementary Movie

This file contains Supplementary Movie 1- Entrainment of rhythmic motor behaviour. The movie shows the tail of a zebrafish larva with its head (outside the movie frame) embedded in the agarose, during the last 4 conditioning stimuli of a series of 20 light flashes (ISI of 6 s) and the first two rhythmic cycles following CS. The tone indicates the onset of the stimuli and the entrained interval time (6 and 12 s) following the CS. Note that during the last two cycles of CS the larva initiated the tail movement shortly before the onset of the light stimulus, suggesting an “anticipatory” motor behaviour. (AVI 31405 kb)

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sumbre, G., Muto, A., Baier, H. et al. Entrained rhythmic activities of neuronal ensembles as perceptual memory of time interval. Nature 456, 102–106 (2008).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing