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Delay activity of specific prefrontal interneuron subtypes modulates memory-guided behavior

Nature Neuroscience volume 20, pages 854863 (2017) | Download Citation

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Abstract

Memory-guided behavior requires maintenance of task-relevant information without sensory input, but the underlying circuit mechanism remains unclear. Calcium imaging in mice performing a delayed Go or No-Go task revealed robust delay activity in dorsomedial prefrontal cortex, with different pyramidal neurons signaling Go and No-Go action plans. Inhibiting pyramidal neurons by optogenetically activating somatostatin- or parvalbumin-positive interneurons, even transiently during the delay, impaired task performance, primarily by increasing inappropriate Go responses. In contrast, activating vasoactive intestinal peptide (VIP)-positive interneurons enhanced behavioral performance and neuronal action plan representation. Furthermore, while endogenous activity of somatostatin and parvalbumin neurons was strongly biased toward Go trials, VIP neurons were similarly active in Go and No-Go trials. Somatostatin or VIP neuron activation also impaired or enhanced performance, respectively, in a delayed two-alternative forced-choice task. Thus, dorsomedial prefrontal cortex is a crucial component of the short-term memory network, and activation of its VIP neurons improves memory retention.

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Change history

  • 04 May 2017

    In the version of this article initially published online, a duplicate of the panel title "Cell 2" was overlaid across the image in Figure 6a. The error has been corrected in the print, PDF and HTML versions of this article.

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Acknowledgements

We thank L. Pinto for helping set up the endoscope imaging system, M. Zhang and N. Perwez for technical assistance, University of North Carolina Virus Core and Penn Vector Core for supplying AAV, and V. Jayaraman, R.A. Kerr, D.S. Kim, L.L. Looger and K. Svoboda from the GENIE Project for providing GCaMP6f. This work was supported by the Uehara Memorial Foundation (T.K.), the Human Frontier Science Program (T.K.), NIH R01 EY018861 (Y.D.) and Howard Hughes Medical Institute (Y.D.).

Author information

Affiliations

  1. Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, California, USA.

    • Tsukasa Kamigaki
    •  & Yang Dan

Authors

  1. Search for Tsukasa Kamigaki in:

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Contributions

T.K. performed all the experiments and analyzed the data. T.K. and Y.D. conceived and designed the experiments and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Yang Dan.

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    Supplementary Figures 1–12

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    Supplementary Methods Checklist

Videos

  1. 1.

    A mouse performing the delayed Go/No-Go auditory task.

    The target and non-target tones used in the task are also included. Lick responses were detected with an infra-red beam running between the optic fibers near the mouth. Play speed, 1x.

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DOI

https://doi.org/10.1038/nn.4554

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