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Fast and slow transitions in frontal ensemble activity during flexible sensorimotor behavior

Nature Neuroscience volume 19, pages 12341242 (2016) | Download Citation

Abstract

The ability to shift between repetitive and goal-directed actions is a hallmark of cognitive control. Previous studies have reported that adaptive shifts in behavior are accompanied by changes of neural activity in frontal cortex. However, neural and behavioral adaptations can occur at multiple time scales, and their relationship remains poorly defined. Here we developed an adaptive sensorimotor decision-making task for head-fixed mice, requiring them to shift flexibly between multiple auditory–motor mappings. Two-photon calcium imaging of secondary motor cortex (M2) revealed different ensemble activity states for each mapping. When adapting to a conditional mapping, transitions in ensemble activity were abrupt and occurred before the recovery of behavioral performance. By contrast, gradual and delayed transitions accompanied shifts toward repetitive responding. These results demonstrate distinct ensemble signatures associated with the start versus end of sensory-guided behavior and suggest that M2 leads in engaging goal-directed response strategies that require sensorimotor associations.

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Acknowledgements

We thank D. Lee, M. Picciotto, and J. Taylor for discussions, and C. Posner and R. Hannibal for assistance with behavioral training. This work was supported by National Institute of Aging center grant P50AG047270 (A.C.K.), National Institute of Mental Health grant R21MH110712 (A.C.K.), NARSAD Young Investigator Award (A.C.K.), National Institutes of Health training grant T32NS041228 (M.J.S.), National Science Foundation Graduate Research Fellowship DGE-1122492 (M.J.S.), and a Brown-Coxe Postdoctoral Fellowship (F.A.).

Author information

Affiliations

  1. Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut, USA.

    • Michael J Siniscalchi
    •  & Alex C Kwan
  2. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.

    • Victoria Phoumthipphavong
    • , Farhan Ali
    • , Marc Lozano
    •  & Alex C Kwan
  3. Department of Neuroscience, Yale University School of Medicine, New Haven, Connecticut, USA.

    • Alex C Kwan

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Contributions

M.J.S. and A.C.K. conceived the project. M.J.S. performed all experiments. V.P. assisted with mouse surgery and inactivation experiments. F.A. and M.L. assisted with behavioral training and histology. M.J.S. and A.C.K. analyzed the data and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Alex C Kwan.

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    Supplementary Figures 1–9 and Supplementary Table 1

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    Supplementary Methods Checklist

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    Supplementary Video 1

    A mouse performing sound-guided trials from the adaptive decision-making task. Video and audio were captured using an infrared webcam.

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DOI

https://doi.org/10.1038/nn.4342

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