Functional organization and population dynamics in the mouse primary auditory cortex

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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.

References

  1. 1

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

  2. 2

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

  3. 3

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

  4. 4

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

  5. 5

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

  6. 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).

  7. 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).

  8. 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).

  9. 9

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

  10. 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).

  11. 11

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

  12. 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).

  13. 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).

  14. 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).

  15. 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).

  16. 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).

  17. 17

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

  18. 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).

  19. 19

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

  20. 20

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

  21. 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).

  22. 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).

  23. 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).

  24. 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).

  25. 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).

  26. 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).

  27. 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).

  28. 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).

  29. 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).

  30. 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).

  31. 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).

  32. 32

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

  33. 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).

  34. 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).

  35. 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).

  36. 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).

  37. 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).

  38. 38

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

  39. 39

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

  40. 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).

  41. 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).

  42. 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).

  43. 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).

  44. 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).

  45. 45

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

  46. 46

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

  47. 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).

  48. 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).

  49. 49

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

  50. 50

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

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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).

Author information

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.

Correspondence to Adi Mizrahi.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

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) doi:10.1038/nn.2484

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