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Functional organization and population dynamics in the mouse primary auditory cortex

Nature Neuroscience volume 13, pages 353–360 (2010)Cite this article

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An Author Correction to this article was published on 25 September 2020

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Abstract

Cortical processing of auditory stimuli involves large populations of neurons with distinct individual response profiles. However, the functional organization and dynamics of local populations in the auditory cortex have remained largely unknown. Using in vivo two-photon calcium imaging, we examined the response profiles and network dynamics of layer 2/3 neurons in the primary auditory cortex (A1) of mice in response to pure tones. We found that local populations in A1 were highly heterogeneous in the large-scale tonotopic organization. Despite the spatial heterogeneity, the tendency of neurons to respond together (measured as noise correlation) was high on average. This functional organization and high levels of noise correlations are consistent with the existence of partially overlapping cortical subnetworks. Our findings may account for apparent discrepancies between ordered large-scale organization and local heterogeneity.

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Figure 1: In vivo two-photon calcium imaging from dozens of neurons simultaneously in A1.
Figure 2: Identification of spike-induced calcium transients.
Figure 3: Single-trial and mean response profiles to pure tones.
Figure 4: Functional micro-architecture in A1 is heterogeneous.
Figure 5: Local populations in A1 are not organized tonotopically.
Figure 6: Signal correlations between neurons in local networks are low on average and are variable and decrease with distance.
Figure 7: Noise correlations in local networks are high on average and variable and decrease with distance.

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  • 25 September 2020

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

References

  1. Averbeck, B.B., Latham, P.E. & Pouget, A. Neural correlations, population coding and computation. Nat. Rev. Neurosci. 7, 358–366 (2006).

    PubMed  CAS  Google Scholar 

  2. Cohen, M.R. & Newsome, W.T. Context-dependent changes in functional circuitry in visual area MT. Neuron 60, 162–173 (2008).

    PubMed  PubMed Central  CAS  Google Scholar 

  3. Houweling, A.R. & Brecht, M. Behavioural report of single neuron stimulation in somatosensory cortex. Nature 451, 65–68 (2008).

    PubMed  CAS  Google Scholar 

  4. Bizley, J.K., Nodal, F.R., Nelken, I. & King, A.J. Functional organization of ferret auditory cortex. Cereb. Cortex 15, 1637–1653 (2005).

    PubMed  Google Scholar 

  5. DeWeese, M.R., Wehr, M. & Zador, A.M. Binary spiking in auditory cortex. J. Neurosci. 23, 7940–7949 (2003).

    PubMed  PubMed Central  CAS  Google Scholar 

  6. Moshitch, D., Las, L., Ulanovsky, N., Bar-Yosef, O. & Nelken, I. Responses of neurons in primary auditory cortex (A1) to pure tones in the halothane-anesthetized cat. J. Neurophysiol. 95, 3756–3769 (2006).

    PubMed  Google Scholar 

  7. Nelken, I. et al. Large-scale organization of ferret auditory cortex revealed using continuous acquisition of intrinsic optical signals. J. Neurophysiol. 92, 2574–2588 (2004).

    PubMed  Google Scholar 

  8. Stiebler, I., Neulist, R., Fichtel, I. & Ehret, G. The auditory cortex of the house mouse: left-right differences, tonotopic organization and quantitative analysis of frequency representation. J. Comp. Physiol. [A] 181, 559–571 (1997).

    CAS  Google Scholar 

  9. Hromádka, T., Deweese, M.R. & Zador, A.M. Sparse representation of sounds in the unanesthetized auditory cortex. PLoS Biol. 6, e16 (2008).

    PubMed  PubMed Central  Google Scholar 

  10. Ohki, K., Chung, S., Ch'ng, Y.H., Kara, P. & Reid, R.C. Functional imaging with cellular resolution reveals precise micro-architecture in visual cortex. Nature 433, 597–603 (2005).

    PubMed  CAS  Google Scholar 

  11. Ohki, K. et al. Highly ordered arrangement of single neurons in orientation pinwheels. Nature 442, 925–928 (2006).

    PubMed  CAS  Google Scholar 

  12. Kerr, J.N. et al. Spatial organization of neuronal population responses in layer 2/3 of rat barrel cortex. J. Neurosci. 27, 13316–13328 (2007).

    PubMed  PubMed Central  CAS  Google Scholar 

  13. Sato, T.R., Gray, N.W., Mainen, Z.F. & Svoboda, K. The functional microarchitecture of the mouse barrel cortex. PLoS Biol. 5, e189 (2007).

    PubMed  PubMed Central  Google Scholar 

  14. Stosiek, C., Garaschuk, O., Holthoff, K. & Konnerth, A. In vivo two-photon calcium imaging of neuronal networks. Proc. Natl. Acad. Sci. USA 100, 7319–7324 (2003).

    PubMed  CAS  Google Scholar 

  15. Llano, D.A. & Sherman, S.M. Evidence for nonreciprocal organization of the mouse auditory thalamocortical-corticothalamic projection systems. J. Comp. Neurol. 507, 1209–1227 (2008).

    PubMed  Google Scholar 

  16. Komai, S., Denk, W., Osten, P., Brecht, M. & Margrie, T.W. Two-photon targeted patching (TPTP) in vivo. Nat. Protoc. 1, 647–652 (2006).

    PubMed  CAS  Google Scholar 

  17. Sadagopan, S. & Wang, X. Level invariant representation of sounds by populations of neurons in primary auditory cortex. J. Neurosci. 28, 3415–3426 (2008).

    PubMed  PubMed Central  CAS  Google Scholar 

  18. Kilgard, M.P. & Merzenich, M.M. Distributed representation of spectral and temporal information in rat primary auditory cortex. Hear. Res. 134, 16–28 (1999).

    PubMed  PubMed Central  CAS  Google Scholar 

  19. Sally, S.L. & Kelly, J.B. Organization of auditory cortex in the albino rat: sound frequency. J. Neurophysiol. 59, 1627–1638 (1988).

    PubMed  CAS  Google Scholar 

  20. Zohary, E., Shadlen, M.N. & Newsome, W.T. Correlated neuronal discharge rate and its implications for psychophysical performance. Nature 370, 140–143 (1994).

    PubMed  CAS  Google Scholar 

  21. Holmgren, C., Harkany, T., Svennenfors, B. & Zilberter, Y. Pyramidal cell communication within local networks in layer 2/3 of rat neocortex. J. Physiol. (Lond.) 551, 139–153 (2003).

    CAS  Google Scholar 

  22. Thomson, A.M., West, D.C., Wang, Y. & Bannister, A.P. Synaptic connections and small circuits involving excitatory and inhibitory neurons in layers 2–5 of adult rat and cat neocortex: triple intracellular recordings and biocytin labeling in vitro. Cereb. Cortex 12, 936–953 (2002).

    PubMed  Google Scholar 

  23. Song, S., Sjostrom, P.J., Reigl, M., Nelson, S. & Chklovskii, D.B. Highly nonrandom features of synaptic connectivity in local cortical circuits. PLoS Biol. 3, e68 (2005).

    PubMed  PubMed Central  Google Scholar 

  24. Abeles, M. & Goldstein, M.H. Jr. Functional architecture in cat primary auditory cortex: columnar organization and organization according to depth. J. Neurophysiol. 33, 172–187 (1970).

    PubMed  CAS  Google Scholar 

  25. Greenberg, D.S., Houweling, A.R. & Kerr, J.N. Population imaging of ongoing neuronal activity in the visual cortex of awake rats. Nat. Neurosci. 11, 749–751 (2008).

    PubMed  CAS  Google Scholar 

  26. Kerr, J.N., Greenberg, D. & Helmchen, F. Imaging input and output of neocortical networks in vivo. Proc. Natl. Acad. Sci. USA 102, 14063–14068 (2005).

    PubMed  CAS  Google Scholar 

  27. Linden, J.F., Liu, R.C., Sahani, M., Schreiner, C.E. & Merzenich, M.M. Spectrotemporal structure of receptive fields in areas AI and AAF of mouse auditory cortex. J. Neurophysiol. 90, 2660–2675 (2003).

    PubMed  Google Scholar 

  28. Wallace, D.J. et al. Single-spike detection in vitro and in vivo with a genetic Ca2+ sensor. Nat. Methods 5, 797–804 (2008).

    PubMed  CAS  Google Scholar 

  29. Kisley, M.A. & Gerstein, G.L. Trial-to-trial variability and state-dependent modulation of auditory-evoked responses in cortex. J. Neurosci. 19, 10451–10460 (1999).

    PubMed  PubMed Central  CAS  Google Scholar 

  30. Zurita, P., Villa, A.E., de Ribaupierre, Y., de Ribaupierre, F. & Rouiller, E.M. Changes of single unit activity in the cat's auditory thalamus and cortex associated to different anesthetic conditions. Neurosci. Res. 19, 303–316 (1994).

    PubMed  CAS  Google Scholar 

  31. Recanzone, G.H., Guard, D.C. & Phan, M.L. Frequency and intensity response properties of single neurons in the auditory cortex of the behaving macaque monkey. J. Neurophysiol. 83, 2315–2331 (2000).

    PubMed  CAS  Google Scholar 

  32. Sadagopan, S. & Wang, X. Nonlinear spectrotemporal interactions underlying selectivity for complex sounds in auditory cortex. J. Neurosci. 29, 11192–11202 (2009).

    PubMed  PubMed Central  CAS  Google Scholar 

  33. Philibert, B. et al. Functional organization and hemispheric comparison of primary auditory cortex in the common marmoset (Callithrix jacchus). J. Comp. Neurol. 487, 391–406 (2005).

    PubMed  Google Scholar 

  34. Evans, E.F., Ross, H.F. & Whitfield, I.C. The spatial distribution of unit characteristic frequency in the primary auditory cortex of the cat. J. Physiol. (Lond.) 179, 238–247 (1965).

    CAS  Google Scholar 

  35. Goldstein, M.H. Jr., Abeles, M., Daly, R.L. & McIntosh, J. Functional architecture in cat primary auditory cortex: tonotopic organization. J. Neurophysiol. 33, 188–197 (1970).

    PubMed  Google Scholar 

  36. Merzenich, M.M. Knight, P.L. & Roth, G.L. Representation of cochlea within primary auditory cortex in the cat. J. Neurophysiol. 38, 231–249 (1975).

    PubMed  CAS  Google Scholar 

  37. Schreiner, C.E. & Sutter, M.L. Topography of excitatory bandwidth in cat primary auditory cortex: single-neuron versus multiple-neuron recordings. J. Neurophysiol. 68, 1487–1502 (1992).

    PubMed  CAS  Google Scholar 

  38. Reale, R.A. & Imig, T.J. Tonotopic organization in auditory cortex of the cat. J. Comp. Neurol. 192, 265–291 (1980).

    PubMed  CAS  Google Scholar 

  39. Henze, D.A. et al. Intracellular features predicted by extracellular recordings in the hippocampus in vivo. J. Neurophysiol. 84, 390–400 (2000).

    PubMed  CAS  Google Scholar 

  40. Margrie, T.W., Brecht, M. & Sakmann, B. In vivo, low-resistance, whole-cell recordings from neurons in the anaesthetized and awake mammalian brain. Pflugers Arch. 444, 491–498 (2002).

    PubMed  CAS  Google Scholar 

  41. Sohya, K., Kameyama, K., Yanagawa, Y., Obata, K. & Tsumoto, T. GABAergic neurons are less selective to stimulus orientation than excitatory neurons in layer II/III of visual cortex, as revealed by in vivo functional Ca2+ imaging in transgenic mice. J. Neurosci. 27, 2145–2149 (2007).

    PubMed  PubMed Central  CAS  Google Scholar 

  42. Mrsic-Flogel, T.D., Versnel, H. & King, A.J. Development of contralateral and ipsilateral frequency representations in ferret primary auditory cortex. Eur. J. Neurosci. 23, 780–792 (2006).

    PubMed  Google Scholar 

  43. Chakraborty, S., Sandberg, A. & Greenfield, S.A. Differential dynamics of transient neuronal assemblies in visual compared to auditory cortex. Exp. Brain Res. 182, 491–498 (2007).

    PubMed  Google Scholar 

  44. Mrsic-Flogel, T.D. et al. Homeostatic regulation of eye-specific responses in visual cortex during ocular dominance plasticity. Neuron 54, 961–972 (2007).

    PubMed  CAS  Google Scholar 

  45. Chechik, G. et al. Reduction of information redundancy in the ascending auditory pathway. Neuron 51, 359–368 (2006).

    PubMed  CAS  Google Scholar 

  46. Wang, X., Lu, T., Snider, R.K. & Liang, L. Sustained firing in auditory cortex evoked by preferred stimuli. Nature 435, 341–346 (2005).

    PubMed  CAS  Google Scholar 

  47. Schulze, H. & Langner, G. Periodicity coding in the primary auditory cortex of the Mongolian gerbil (Meriones unguiculatus): two different coding strategies for pitch and rhythm? J. Comp. Physiol. [A] 181, 651–663 (1997).

    CAS  Google Scholar 

  48. Schneidman, E., Berry, M.J. II, Segev, R. & Bialek, W. Weak pair-wise correlations imply strongly correlated network states in a neural population. Nature 440, 1007–1012 (2006).

    PubMed  PubMed Central  CAS  Google Scholar 

  49. Sompolinsky, H., Yoon, H., Kang, K. & Shamir, M. Population coding in neuronal systems with correlated noise. Phys. Rev. E 64, 051904 (2001).

    CAS  Google Scholar 

  50. Yoshimura, Y., Dantzker, J.L. & Callaway, E.M. Excitatory cortical neurons form fine-scale functional networks. Nature 433, 868–873 (2005).

    PubMed  CAS  Google Scholar 

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Acknowledgements

We thank H. Sompolinsky and E. Zohary for critically commenting on early versions of this manuscript. We thank N. Taaseh and A. Yaron-Jakoubovitch for their kind technical assistance during the early stages of this project. We thank Y. Rubin and J. Schiller for the software module of the line scan. We thank J. Linden for her help on cortical recordings in mice. We thank all the members of the Mizrahi laboratory and A. Eban-Rothschild for their helpful comments and discussions. This work was supported in part by a grant from Citizens United for Research in Epilepsy and by a European Research Council grant to A.M. (#203994), and by a grant of the European Union FP6 to I.N. (NOVELTUNE consortium).

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Authors and Affiliations

  1. Department of Neurobiology, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel

    Gideon Rothschild, Israel Nelken & Adi Mizrahi

  2. The Interdisciplinary Center for Neural Computation, The Hebrew University of Jerusalem, Jerusalem, Israel

    Gideon Rothschild, Israel Nelken & Adi Mizrahi

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  1. Gideon Rothschild
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G.R., I.N. and A.M. designed the experiments together and wrote the paper together. G.R. performed the experiments and analyzed the data.

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Correspondence to Adi Mizrahi.

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Supplementary Figures 1–7 and Supplementary Discussion (PDF 2835 kb)

Supplementary Movie 1

Image stack from A1 following Fluo4-AM and SR101 loading. (WMV 5966 kb)

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Rothschild, G., Nelken, I. & Mizrahi, A. Functional organization and population dynamics in the mouse primary auditory cortex. Nat Neurosci 13, 353–360 (2010). https://doi.org/10.1038/nn.2484

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