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.

  • Article
  • Published:

Unique functional properties of somatostatin-expressing GABAergic neurons in mouse barrel cortex

This article has been updated

Abstract

Neocortical GABAergic neurons have diverse molecular, structural and electrophysiological features, but the functional correlates of this diversity are largely unknown. We found unique membrane potential dynamics of somatostatin-expressing (SOM) neurons in layer 2/3 of the primary somatosensory barrel cortex of awake behaving mice. SOM neurons were spontaneously active during periods of quiet wakefulness. However, SOM neurons hyperpolarized and reduced action potential firing in response to both passive and active whisker sensing, in contrast with all other recorded types of nearby neurons, which were excited by sensory input. Optogenetic inhibition of SOM neurons increased burst firing in nearby excitatory neurons. We hypothesize that the spontaneous activity of SOM neurons during quiet wakefulness provides a tonic inhibition to the distal dendrites of excitatory pyramidal neurons. Conversely, the inhibition of SOM cells during active cortical processing likely enhances distal dendritic excitability, which may be important for top-down computations and sensorimotor integration.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1: Unique membrane potential dynamics of SOM neurons during quiet wakefulness.
Figure 2: Sensory stimulation hyperpolarizes SOM cells.
Figure 3: SOM cells hyperpolarize during active whisking and active touch.
Figure 4: Optogenetic inhibition of SOM neurons increases action potential firing and burst firing in nearby excitatory neurons.

Similar content being viewed by others

Change history

  • 04 March 2012

    In the version of this article initially published online, the legend for Supplementary Movie 1 was missing. The error has been corrected for the HTML version of this article.

References

  1. Freund, T.F. & Buzsáki, G. Interneurons of the hippocampus. Hippocampus 6, 347–470 (1996).

    Article  CAS  Google Scholar 

  2. Markram, H. et al. Interneurons of the neocortical inhibitory system. Nat. Rev. Neurosci. 5, 793–807 (2004).

    Article  CAS  Google Scholar 

  3. Ascoli, G.A. et al. Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex. Nat. Rev. Neurosci. 9, 557–568 (2008).

    Article  CAS  Google Scholar 

  4. Burkhalter, A. Many specialists for suppressing cortical excitation. Front. Neurosci. 2, 155–167 (2008).

    Article  CAS  Google Scholar 

  5. Klausberger, T. & Somogyi, P. Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations. Science 321, 53–57 (2008).

    Article  CAS  Google Scholar 

  6. Margrie, T.W. et al. Targeted whole-cell recordings in the mammalian brain in vivo. Neuron 39, 911–918 (2003).

    Article  CAS  Google Scholar 

  7. Gentet, L.J., Avermann, M., Matyas, F., Staiger, J.F. & Petersen, C.C.H. Membrane potential dynamics of GABAergic neurons in the barrel cortex of behaving mice. Neuron 65, 422–435 (2010).

    Article  CAS  Google Scholar 

  8. Mateo, C. et al. In vivo optogenetic stimulation of neocortical excitatory neurons drives brain-state-dependent inhibition. Curr. Biol. 21, 1593–1602 (2011).

    Article  CAS  Google Scholar 

  9. Brecht, M. Barrel cortex and whisker-mediated behaviors. Curr. Opin. Neurobiol. 17, 408–416 (2007).

    Article  CAS  Google Scholar 

  10. Petersen, C.C.H. The functional organization of the barrel cortex. Neuron 56, 339–355 (2007).

    Article  CAS  Google Scholar 

  11. Diamond, M.E., von Heimendahl, M., Knutsen, P.M., Kleinfeld, D. & Ahissar, E. 'Where' and 'what' in the whisker sensorimotor system. Nat. Rev. Neurosci. 9, 601–612 (2008).

    Article  CAS  Google Scholar 

  12. Lee, S., Hjerling-Leffler, J., Zagha, E., Fishell, G. & Rudy, B. The largest group of superficial neocortical GABAergic interneurons expresses ionotropic serotonin receptors. J. Neurosci. 30, 16796–16808 (2010).

    Article  CAS  Google Scholar 

  13. Bartos, M., Vida, I. & Jonas, P. Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks. Nat. Rev. Neurosci. 8, 45–56 (2007).

    Article  CAS  Google Scholar 

  14. Freund, T.F. & Katona, I. Perisomatic inhibition. Neuron 56, 33–42 (2007).

    Article  CAS  Google Scholar 

  15. Somogyi, P. A specific 'axo-axonal' interneuron in the visual cortex of the rat. Brain Res. 136, 345–350 (1977).

    Article  CAS  Google Scholar 

  16. Oláh, S. et al. Regulation of cortical microcircuits by unitary GABA-mediated volume transmission. Nature 461, 1278–1281 (2009).

    Article  Google Scholar 

  17. Acsády, L., Görcs, T.J. & Freund, T.F. Different populations of vasoactive intestinal polypeptide-immunoreactive interneurons are specialized to control pyramidal cells or interneurons in the hippocampus. Neuroscience 73, 317–334 (1996).

    Article  Google Scholar 

  18. Dalezios, Y., Luján, R., Shigemoto, R., Roberts, J.D. & Somogyi, P. Enrichment of mGluR7a in the presynaptic active zones of GABAergic and non-GABAergic terminals on interneurons in the rat somatosensory cortex. Cereb. Cortex 12, 961–974 (2002).

    Article  Google Scholar 

  19. Staiger, J.F., Masanneck, C., Schleicher, A. & Zuschratter, W. Calbindin-containing interneurons are a target for VIP-immunoreactive synapses in rat primary somatosensory cortex. J. Comp. Neurol. 468, 179–189 (2004).

    Article  CAS  Google Scholar 

  20. Dávid, C., Schleicher, A., Zuschratter, W. & Staiger, J.F. The innervation of parvalbumin-containing interneurons by VIP-immunopositive interneurons in the primary somatosensory cortex of the adult rat. Eur. J. Neurosci. 25, 2329–2340 (2007).

    Article  Google Scholar 

  21. Wang, Y. et al. Anatomical, physiological and molecular properties of Martinotti cells in the somatosensory cortex of the juvenile rat. J. Physiol. (Lond.) 561, 65–90 (2004).

    Article  CAS  Google Scholar 

  22. Ma, Y., Hu, H., Berrebi, A.S., Mathers, P.H. & Agmon, A. Distinct subtypes of somatostatin-containing neocortical interneurons revealed in transgenic mice. J. Neurosci. 26, 5069–5082 (2006).

    Article  CAS  Google Scholar 

  23. Kapfer, C., Glickfeld, L.L., Atallah, B.V. & Scanziani, M. Supralinear increase of recurrent inhibition during sparse activity in the somatosensory cortex. Nat. Neurosci. 10, 743–753 (2007).

    Article  CAS  Google Scholar 

  24. Silberberg, G. & Markram, H. Disynaptic inhibition between neocortical pyramidal cells mediated by Martinotti cells. Neuron 53, 735–746 (2007).

    Article  CAS  Google Scholar 

  25. McGarry, L.M. et al. Quantitative classification of somatostatin-positive neocortical interneurons identifies three interneuron subtypes. Front. Neural Circuits 4, 12 (2010).

    PubMed  PubMed Central  Google Scholar 

  26. Reyes, A. et al. Target cell–specific facilitation and depression in neocortical circuits. Nat. Neurosci. 1, 279–285 (1998).

    Article  CAS  Google Scholar 

  27. Fanselow, E.E., Richardson, K.A. & Connors, B.W. Selective, state-dependent activation of somatostatin-expressing inhibitory interneurons in mouse neocortex. J. Neurophysiol. 100, 2640–2652 (2008).

    Article  Google Scholar 

  28. Fino, E. & Yuste, R. Dense inhibitory connectivity in neocortex. Neuron 69, 1188–1203 (2011).

    Article  CAS  Google Scholar 

  29. Packer, A.M. & Yuste, R. Dense, unspecific connectivity of neocortical parvalbumin-positive interneurons: a canonical microcircuit for inhibition? J. Neurosci. 31, 13260–13271 (2011).

    Article  CAS  Google Scholar 

  30. Tamamaki, N. et al. Green fluorescent protein expression and colocalization with calretinin, parvalbumin, and somatostatin in the GAD67-GFP knock-in mouse. J. Comp. Neurol. 467, 60–79 (2003).

    Article  CAS  Google Scholar 

  31. Oliva, A.A., Jiang, M., Lam, T., Smith, K.L. & Swann, J.W. Novel hippocampal interneuronal subtypes identified using transgenic mice that express green fluorescent protein in GABAergic interneurons. J. Neurosci. 20, 3354–3368 (2000).

    Article  CAS  Google Scholar 

  32. Suzuki, N. & Bekkers, J.M. Inhibitory neurons in the anterior piriform cortex of the mouse: classification using molecular markers. J. Comp. Neurol. 518, 1670–1687 (2010).

    Article  CAS  Google Scholar 

  33. Poulet, J.F.A. & Petersen, C.C.H. Internal brain state regulates membrane potential synchrony in barrel cortex of behaving mice. Nature 454, 881–885 (2008).

    Article  CAS  Google Scholar 

  34. Crochet, S., Poulet, J.F.A., Kremer, Y. & Petersen, C.C.H. Synaptic mechanisms underlying sparse coding of active touch. Neuron 69, 1160–1175 (2011).

    Article  CAS  Google Scholar 

  35. Okun, M. & Lampl, I. Instantaneous correlation of excitation and inhibition during ongoing and sensory-evoked activities. Nat. Neurosci. 11, 535–537 (2008).

    Article  CAS  Google Scholar 

  36. O'Connor, D.H., Peron, S.P., Huber, D. & Svoboda, K. Neural activity in barrel cortex underlying vibrissa-based object localization in mice. Neuron 67, 1048–1061 (2010).

    Article  CAS  Google Scholar 

  37. Larkum, M.E., Zhu, J.J. & Sakmann, B. A new cellular mechanism for coupling inputs arriving at different cortical layers. Nature 398, 338–341 (1999).

    Article  CAS  Google Scholar 

  38. Losonczy, A., Makara, J.K. & Magee, J.C. Compartmentalized dendritic plasticity and input feature storage in neurons. Nature 452, 436–441 (2008).

    Article  CAS  Google Scholar 

  39. Larkum, M.E., Nevian, T., Sandler, M., Polsky, A. & Schiller, J. Synaptic integration in tuft dendrites of layer 5 pyramidal neurons: a new unifying principle. Science 325, 756–760 (2009).

    Article  CAS  Google Scholar 

  40. Branco, T. & Häusser, M. Synaptic integration gradients in single cortical pyramidal cell dendrites. Neuron 69, 885–892 (2011).

    Article  CAS  Google Scholar 

  41. Tian, L. et al. Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators. Nat. Methods 6, 875–881 (2009).

    Article  CAS  Google Scholar 

  42. Gradinaru, V. et al. Molecular and cellular approaches for diversifying and extending optogenetics. Cell 141, 154–165 (2010).

    Article  CAS  Google Scholar 

  43. Taniguchi, H. et al. A resource of Cre driver lines for genetic targeting of GABAergic neurons in cerebral cortex. Neuron 71, 995–1013 (2011).

    Article  CAS  Google Scholar 

  44. Xu, X. & Callaway, E.M. Laminar specificity of functional input to distinct types of inhibitory cortical neurons. J. Neurosci. 29, 70–85 (2009).

    Article  CAS  Google Scholar 

  45. Petreanu, L., Mao, T., Sternson, S.M. & Svoboda, K. The subcellular organization of neocortical excitatory connections. Nature 457, 1142–1145 (2009).

    Article  CAS  Google Scholar 

  46. Curtis, J.C. & Kleinfeld, D. Phase-to-rate transformations encode touch in cortical neurons of a scanning sensorimotor system. Nat. Neurosci. 12, 492–501 (2009).

    Article  CAS  Google Scholar 

  47. Gilbert, C.D. & Sigman, M. Brain states: top-down influences in sensory processing. Neuron 54, 677–696 (2007).

    Article  CAS  Google Scholar 

  48. Holtmaat, A. et al. Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window. Nat. Protoc. 4, 1128–1144 (2009).

    Article  CAS  Google Scholar 

  49. Langer, D., van t'Hoff, M. & Helmchen, F. Helioscan, a highly versatile control software for laser-scanning microscopes written in LabVIEW. Brain Research Institute, University of Zurich, Switzerland (http://www.helioscan.org/) (2010).

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

    Article  Google Scholar 

Download references

Acknowledgements

We thank L. Looger (Howard Hughes Medical Institute, Janelia Farm) for GCaMP3 and K. Deisseroth (Stanford University) for eNpHR3.0. This work was funded by grants from the Swiss National Science Foundation (C.C.H.P.), Human Frontiers in Science Program (C.C.H.P.), SystemsX.ch (C.C.H.P.) and Deutsche Forschungsgemeinschaft (Sta 431/8-1, 10-1 to J.F.S.), and a joint Deutsche Forschungsgemeinschaft/Swiss National Science Foundation grant Bacofun (C.C.H.P. and J.F.S.).

Author information

Authors and Affiliations

Authors

Contributions

L.J.G. carried out all of the membrane potential recordings and analyzed the data. Y.K. carried out all of the GCaMP3 imaging experiments and analyzed the data. H.T. and Z.J.H. provided unpublished genetically engineered mice. J.F.S. carried out all of the immunohistochemistry and analyzed the data. C.C.H.P. contributed to the design of experiments, supervised the project and wrote the manuscript. All of the authors commented on the manuscript.

Corresponding author

Correspondence to Carl C H Petersen.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–9 (PDF 6653 kb)

Supplementary Movie 1

GCaMP3 was expressed in excitatory neurons of the barrel cortex of an Emx1-Cre mouse using an AAV-FLEX vector. Fluorescence of layer 1 dendrites in the awake head-restrained mouse was imaged using a two-photon microscope. Whisker movements were filmed simultaneously with the calcium imaging. When the mouse moves its whiskers, the dendrites in layer 1 increase fluorescence. (MOV 12306 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gentet, L., Kremer, Y., Taniguchi, H. et al. Unique functional properties of somatostatin-expressing GABAergic neurons in mouse barrel cortex. Nat Neurosci 15, 607–612 (2012). https://doi.org/10.1038/nn.3051

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn.3051

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