Skip to main content

Thank you for visiting nature.com. 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.

  • Brief Communication
  • Published:

An inhibitory pull–push circuit in frontal cortex

Nature Neuroscience volume 20, pages 389–392 (2017)Cite this article

Subjects

Abstract

Push–pull is a canonical computation of excitatory cortical circuits. By contrast, we identify a pull–push inhibitory circuit in frontal cortex that originates in vasoactive intestinal polypeptide (VIP)-expressing interneurons. During arousal, VIP cells rapidly and directly inhibit pyramidal neurons; VIP cells also indirectly excite these pyramidal neurons via parallel disinhibition. Thus, arousal exerts a feedback pull–push influence on excitatory neurons—an inversion of the canonical push–pull of feedforward input.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: A stable subset of excitatory neurons is inhibited during arousal.
Figure 2: Covariation of coefficients between VIP and Pyr cells across mice.
Figure 3: VIP cells act as a pull–push circuit in vivo.

Similar content being viewed by others

References

  1. Chen, T.W. et al. Nature 499, 295–300 (2013).

    Article  CAS  Google Scholar 

  2. McGinley, M.J., David, S.V. & McCormick, D.A. Neuron 87, 179–192 (2015).

    Article  CAS  Google Scholar 

  3. Ebitz, R.B. & Platt, M.L. Neuron 85, 628–640 (2015).

    Article  CAS  Google Scholar 

  4. Zekveld, A.A., Heslenfeld, D.J., Johnsrude, I.S., Versfeld, N.J. & Kramer, S.E. Neuroimage 101, 76–86 (2014).

    Article  Google Scholar 

  5. Vinck, M., Batista-Brito, R., Knoblich, U. & Cardin, J.A. Neuron 86, 740–754 (2015).

    Article  CAS  Google Scholar 

  6. Niell, C.M. & Stryker, M.P. Neuron 65, 472–479 (2010).

    Article  CAS  Google Scholar 

  7. Polack, P.O., Friedman, J. & Golshani, P. Nat. Neurosci. 16, 1331–1339 (2013).

    Article  CAS  Google Scholar 

  8. Mineault, P.J., Tring, E., Trachtenberg, J.T. & Ringach, D.L. J. Neurosci. 36, 6382–6392 (2016).

    Article  CAS  Google Scholar 

  9. Letzkus, J.J., Wolff, S.B. & Lüthi, A. Neuron 88, 264–276 (2015).

    Article  CAS  Google Scholar 

  10. Pfeffer, C.K., Xue, M., He, M., Huang, Z.J. & Scanziani, M. Nat. Neurosci. 16, 1068–1076 (2013).

    Article  CAS  Google Scholar 

  11. Lee, S., Kruglikov, I., Huang, Z.J., Fishell, G. & Rudy, B. Nat. Neurosci. 16, 1662–1670 (2013).

    Article  CAS  Google Scholar 

  12. Pi, H.J. et al. Nature 503, 521–524 (2013).

    Article  CAS  Google Scholar 

  13. Petreanu, L., Huber, D., Sobczyk, A. & Svoboda, K. Nat. Neurosci. 10, 663–668 (2007).

    Article  CAS  Google Scholar 

  14. Karnani, M.M. et al. J. Neurosci. 36, 3471–3480 (2016).

    Article  CAS  Google Scholar 

  15. Fu, Y. et al. Cell 156, 1139–1152 (2014).

    Article  CAS  Google Scholar 

  16. Anderson, J.S., Carandini, M. & Ferster, D. J. Neurophysiol. 84, 909–926 (2000).

    Article  CAS  Google Scholar 

  17. Douglas, R.J. & Martin, K.A. J. Physiol. (Lond.) 440, 735–769 (1991).

    Article  CAS  Google Scholar 

  18. Huber, D. et al. Nature 484, 473–478 (2012).

    Article  CAS  Google Scholar 

  19. Greenberg, D.S. & Kerr, J.N. J. Neurosci. Methods 176, 1–15 (2009).

    Article  Google Scholar 

  20. Smith, S.L. & Häusser, M. Nat. Neurosci. 13, 1144–1149 (2010).

    Article  CAS  Google Scholar 

  21. Ozden, I., Lee, H.M., Sullivan, M.R. & Wang, S.S. J. Neurophysiol. 100, 495–503 (2008).

    Article  Google Scholar 

Download references

Acknowledgements

This work was funded by R01 EY023871 (JTT), R01 EY018322 (DLR) and R01 EB022915 (DLR). PGJC was supported by postdoctoral Fellowship EX2009-0750 from the Spanish Ministry of Education, Culture and Sport and by postdoctoral contract from Junta de Andalucía (P12-CTS-2232).

Author information

Authors and Affiliations

  1. Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA

    Pablo Garcia-Junco-Clemente, Elaine Tring, Dario L Ringach & Joshua T Trachtenberg

  2. Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla and Departamento de Fisiología Médica y Biofísica, Instituto de Biomedicina de Sevilla, IBiS, Universidad de Sevilla, and CIBERNED, Seville, Spain

    Pablo Garcia-Junco-Clemente

  3. Department of Anatomy & Neurobiology, University of California, Irvine, Irvine, California, USA

    Taruna Ikrar & Xiangmin Xu

  4. Department of Psychology, University of California, Los Angeles, Los Angeles, California, USA

    Dario L Ringach

Authors
  1. Pablo Garcia-Junco-Clemente
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Taruna Ikrar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elaine Tring
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiangmin Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dario L Ringach
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joshua T Trachtenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

P.G.-J.-C. collected and analyzed the data in Figures 1 and 2 and Supplementary Figures 1, 2, 3. D.L.R. analyzed the covariance data in Figure 2. E.T., D.L.R. and J.T.T. contributed to the in vivo photostimulation experiments in Figure 3. T.I. and X.X. contributed to the slice ChR2 mapping data in Figure 3.

Corresponding author

Correspondence to Pablo Garcia-Junco-Clemente.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Integrated supplementary information

Supplementary Figure 1 Overview of experimental setup.

(a) Schematic representation of the approach to viral infection and in vivo imaging. (b)Top: diagram of the genetic cross used to generate mice in which all inhibitory neurons expressed tdTomato. Middle left: cropped image showing GCaMP6 and tdTomato expression in FrA. Bottom left: z-scored time series GCaMP6s responses for 50 excitatory neurons imaged over 10 minutes. Middle right: example traces from 3 excitatory neurons and 2 inhibitory neurons. Traces are z-scored. Excitatory neurons show fast, large amplitude responses, whereas inhibitory neurons show slower, smaller amplitude responses. Bottom right: z-scored traces of ball motion (gray) and pupil diameter (black) imaged over 10 minutes. Note that as locomotion increases, so does pupil diameter.

Supplementary Figure 2 Responses of excitatory neurons expressing GCaMP6-fast.

(a) Ordinate: plot of the correlation coefficients between excitatory response and locomotion. Abscissa: plot of the correlation coefficients between those same neurons and pupil diameter. All neurons recorded are plotted. Note that the activities of many excitatory neurons are suppressed by locomotion and increased pupil diameter. n=3248 neurons, 11 mice, 22 fields of view. (b) Histograms plotting excitatory correlation coefficients to running (top) and pupil diameter (bottom). A Gaussian distribution was fitted to each histogram (black dashed line). Gray lines in both show the cumulative distributions. Note that the coefficients are normally distributed, with roughly half of responses showing negative coefficients. (c) Example traces from 5 excitatory neurons whose activities are negatively (red, left), positively (green, middle), or un-correlated (blue, right) with locomotion/pupil diameter. Cells were taken from the pool of neurons shown in the colored circles in panel a.

Supplementary Figure 3 GCAMP6-slow responses of VIP and SOM interneurons.

Top 4 panels: SOM cell responses.

(a) z-scored time series GCaMP6s responses in 41 SOM cells imaged over 7 minutes. The black trace at the top plots represents the z-scored running speed. (b) Plot of correlation coefficients between GCaMP6s response and running speed (ordinate) and pupil diameter (abscissa). Responses of 2 individual SOM cells are shown in the green and red traces. n=417 neurons, 7 mice, 12 fields of view. (c) Histograms of correlation coefficients between neural response and pupil diameter (left) and running speed (right). Both plots are fitted with a Gaussian (black dashed lines), and the cumulative distributions are plotted (gray lines). Note that SOM cells are strongly left-shifted in their responses with the clear majority negatively correlated with arousal.

Bottom 4 panels: VIP cell responses.

(d) z-scored time series GCaMP6s responses in 44 VIP cells imaged over 6 minutes. Again, the black trace at the top plots is the z-scored running speed. (e-f) Same plots as in panels b-c, but for VIP cells. Note the opposite response of VIP cells to arousal. n=875 neurons, 7 mice, 16 fields of view. (g) The Gaussian distributions plotted in panels c and f are over-plotted to show more clearly the opposite responsiveness of the SOM (red) and VIP (blue) cells during heightened arousal.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Garcia-Junco-Clemente, P., Ikrar, T., Tring, E. et al. An inhibitory pull–push circuit in frontal cortex. Nat Neurosci 20, 389–392 (2017). https://doi.org/10.1038/nn.4483

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn.4483

This article is cited by

Search

Advanced search

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