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Simultaneous cellular-resolution optical perturbation and imaging of place cell firing fields

Nature Neuroscience volume 17, pages 18161824 (2014) | Download Citation

Abstract

Linking neural microcircuit function to emergent properties of the mammalian brain requires fine-scale manipulation and measurement of neural activity during behavior, where each neuron's coding and dynamics can be characterized. We developed an optical method for simultaneous cellular-resolution stimulation and large-scale recording of neuronal activity in behaving mice. Dual-wavelength two-photon excitation allowed largely independent functional imaging with a green fluorescent calcium sensor (GCaMP3, λ = 920 ± 6 nm) and single-neuron photostimulation with a red-shifted optogenetic probe (C1V1, λ = 1,064 ± 6 nm) in neurons coexpressing the two proteins. We manipulated task-modulated activity in individual hippocampal CA1 place cells during spatial navigation in a virtual reality environment, mimicking natural place-field activity, or 'biasing', to reveal subthreshold dynamics. Notably, manipulating single place-cell activity also affected activity in small groups of other place cells that were active around the same time in the task, suggesting a functional role for local place cell interactions in shaping firing fields.

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Acknowledgements

We thank D. Kim and C. Guo (Genetically Encoded Neuronal Indicator and Effector Project, Janelia Research Campus) for transgenic mice, D. Aronov for VR software, B. Scott for discussions, and C. Domnisoru, A. Miri, F. Collman and S. Wang for comments on the manuscript. This work was supported by the US National Institutes of Health (R01-MH083686; P50-GM071508) and a National Science Foundation Graduate Research Fellowship to J.P.R.

Author information

Affiliations

  1. Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey, USA.

    • John Peter Rickgauer
    •  & David W Tank
  2. Bezos Center for Neural Circuit Dynamics, Princeton University, Princeton, New Jersey, USA.

    • John Peter Rickgauer
    •  & David W Tank
  3. Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, USA.

    • John Peter Rickgauer
    •  & David W Tank
  4. Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA.

    • John Peter Rickgauer
    •  & David W Tank
  5. Department of Bioengineering, Stanford University, Stanford, California, USA.

    • Karl Deisseroth
  6. CNC Program, Stanford University, Stanford, California, USA.

    • Karl Deisseroth
  7. Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, USA.

    • Karl Deisseroth
  8. Howard Hughes Medical Institute, Stanford University, Stanford, California, USA.

    • Karl Deisseroth

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Contributions

J.P.R. and D.W.T. designed the study. K.D. contributed reagents. J.P.R. and D.W.T. performed the experiments. J.P.R. analyzed data with strategy and methods contributions from D.W.T. J.P.R. and D.W.T. wrote the paper with comments from K.D.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to David W Tank.

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DOI

https://doi.org/10.1038/nn.3866

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