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Excitatory cortical neurons form fine-scale functional networks

Abstract

The specificity of cortical neuron connections creates columns of functionally similar neurons spanning from the pia to the white matter1,2,3,4,5,6. Here we investigate whether there is an additional, finer level of specificity that creates subnetworks of excitatory neurons within functional columns. We tested for fine-scale specificity of connections to cortical layer 2/3 pyramidal neurons in rat visual cortex by using cross-correlation analyses of synaptic currents evoked by photostimulation. Recording simultaneously from adjacent layer 2/3 pyramidal cells, we find that when they are connected to each other (20% of all recorded pairs) they share common input from layer 4 and within layer 2/3. When adjacent layer 2/3 neurons are not connected to each other, they share very little (if any) common excitatory input from layers 4 and 2/3. In contrast, all layer 2/3 neurons share common excitatory input from layer 5 and inhibitory input from layers 2/3 and 4, regardless of whether they are connected to each other. Thus, excitatory connections from layer 4 to layer 2/3 and within layer 2/3 form fine-scale assemblies of selectively interconnected neurons; inhibitory connections and excitatory connections from layer 5 link neurons across these fine-scale subnetworks. Relatively independent subnetworks of excitatory neurons are therefore embedded within the larger-scale functional architecture; this allows neighbouring neurons to convey information more independently than suggested by previous descriptions of cortical circuitry.

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Figure 1: Cross-correlation analyses of photostimulation-evoked excitatory postsynaptic currents (EPSCs) simultaneously recorded in adjacent pairs of layer 2/3 pyramidal neurons.
Figure 2: Correlation probabilities for EPSCs and IPSCs in layer 2/3 pyramidal cell pairs.
Figure 3: Cross-correlation analyses of photostimulation-evoked inhibitory postsynaptic currents (IPSCs) simultaneously recorded in adjacent pairs of layer 2/3 pyramidal neurons.
Figure 4: Schematic diagram illustrating the organization of cortical connections proposed in this study.

References

  1. Mountcastle, V. B. Introduction. Computation in cortical columns. Cereb. Cortex 13, 2–4 (2003)

    Article  Google Scholar 

  2. Hubel, D. H. & Wiesel, T. N. Receptive fields, binocular interaction and functional architecture in the cat's visual cortex. J. Physiol. (Lond.) 160, 106–154 (1962)

    CAS  Article  Google Scholar 

  3. Chapman, B., Zahs, K. R. & Stryker, M. P. Relation of cortical cell orientation selectivity to alignment of receptive fields of the geniculocortical afferents that arborize within a single orientation column in ferret visual cortex. J. Neurosci. 11, 1347–1358 (1991)

    CAS  Article  Google Scholar 

  4. Ferster, D., Chung, S. & Wheat, H. Orientation selectivity of thalamic input to simple cells of cat visual cortex. Nature 380, 249–252 (1996)

    ADS  CAS  Article  Google Scholar 

  5. Alonso, J. M., Usrey, W. M. & Reid, R. C. Rules of connectivity between geniculate cells and simple cells in cat primary visual cortex. J. Neurosci. 21, 4002–4015 (2001)

    CAS  Article  Google Scholar 

  6. Mooser, F., Bosking, W. H. & Fitzpatrick, D. A morphological basis for orientation tuning in primary visual cortex. Nature Neurosci. 7, 872–879 (2004)

    CAS  Article  Google Scholar 

  7. Callaway, E. M. Local circuits in primary visual cortex of the macaque monkey. Annu. Rev. Neurosci. 21, 47–74 (1998)

    CAS  Article  Google Scholar 

  8. Thomson, A. M. & Morris, O. T. Selectivity in the inter-laminar connections made by neocortical neurones. J. Neurocytol. 31, 239–246 (2002)

    Article  Google Scholar 

  9. 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 labelling in vitro . Cereb. Cortex 12, 936–953 (2002)

    Article  Google Scholar 

  10. Hellwig, B. A quantitative analysis of the local connectivity between pyramidal neurons in layers 2/3 of the rat visual cortex. Biol. Cybern. 82, 111–121 (2000)

    CAS  Article  Google Scholar 

  11. Hellwig, B., Schuz, A. & Aertsen, A. Synapses on axon collaterals of pyramidal cells are spaced at random intervals: a Golgi study in the mouse cerebral cortex. Biol. Cybern. 71, 1–12 (1994)

    CAS  Article  Google Scholar 

  12. Braitenberg, V. & Schuz, A. Anatomy of the Cortex (Springer-Verlag, Berlin, 1991)

    Book  Google Scholar 

  13. Binzegger, T., Douglas, R. J. & Martin, K. A. A quantitative map of the circuit of cat primary visual cortex. J. Neurosci. 24, 8441–8453 (2004)

    CAS  Article  Google Scholar 

  14. Aertsen, A. M., Gerstein, G. L., Habib, M. K. & Palm, G. Dynamics of neuronal firing correlation: modulation of “effective connectivity”. J. Neurophysiol. 61, 900–917 (1989)

    CAS  Article  Google Scholar 

  15. Dantzker, J. L. & Callaway, E. M. Laminar sources of synaptic input to cortical inhibitory interneurons and pyramidal neurons. Nature Neurosci. 3, 701–707 (2000)

    CAS  Article  Google Scholar 

  16. Kawaguchi, Y. & Kondo, S. Parvalbumin, somatostatin and cholecystokinin as chemical markers for specific GABAergic interneuron types in the rat frontal cortex. J. Neurocytol. 31, 277–287 (2002)

    Article  Google Scholar 

  17. Hebb, D. O. The Organization of Behavior (Wiley, New York, 1949)

    Google Scholar 

  18. Yoshimura, Y., Ohmura, T. & Komatsu, Y. Two forms of synaptic plasticity with distinct dependence on age, experience, and NMDA receptor subtype in rat visual cortex. J. Neurosci. 23, 6557–6566 (2003)

    CAS  Article  Google Scholar 

  19. Sur, M., Schummers, J. & Dragoi, V. Cortical plasticity: time for a change. Curr. Biol. 12, R168–R170 (2002)

    CAS  Article  Google Scholar 

  20. Katz, L. C. & Shatz, C. J. Synaptic activity and the construction of cortical circuits. Science 274, 1133–1138 (1996)

    ADS  CAS  Article  Google Scholar 

  21. Sawatari, A. & Callaway, E. M. Diversity and cell type specificity of local excitatory connections to neurons in layer 3B of monkey primary visual cortex. Neuron 25, 459–471 (2000)

    CAS  Article  Google Scholar 

  22. Schubert, D., Kotter, R., Zilles, K., Luhmann, H. J. & Staiger, J. F. Cell type-specific circuits of cortical layer IV spiny neurons. J. Neurosci. 23, 2961–2970 (2003)

    CAS  Article  Google Scholar 

  23. Agmon, A. & Connors, B. W. Correlation between intrinsic firing patterns and thalamocortical synaptic responses of neurons in mouse barrel cortex. J. Neurosci. 12, 319–329 (1992)

    CAS  Article  Google Scholar 

  24. Gibson, J. R., Beierlein, M. & Connors, B. W. Two networks of electrically coupled inhibitory neurons in neocortex. Nature 402, 75–79 (1999)

    ADS  CAS  Article  Google Scholar 

  25. Gonchar, Y. & Burkhalter, A. Connectivity of GABAergic calretinin-immunoreactive neurons in rat primary visual cortex. Cereb. Cortex 9, 683–696 (1999)

    CAS  Article  Google Scholar 

  26. Gonchar, Y. & Burkhalter, A. Distinct GABAergic targets of feedforward and feedback connections between lower and higher areas of rat visual cortex. J. Neurosci. 23, 10904–10912 (2003)

    CAS  Article  Google Scholar 

  27. Meskenaite, V. Calretinin-immunoreactive local circuit neurons in area 17 of the cynomolgus monkey, Macaca fascicularis. J. Comp. Neurol. 379, 113–132 (1997)

    CAS  Article  Google Scholar 

  28. Staiger, J. F. et al. Innervation of interneurons immunoreactive for VIP by intrinsically bursting pyramidal cells and fast-spiking interneurons in infragranular layers of juvenile rat neocortex. Eur. J. Neurosci. 16, 11–20 (2002)

    Article  Google Scholar 

  29. Girman, S. V., Sauve, Y. & Lund, R. D. Receptive field properties of single neurons in rat primary visual cortex. J. Neurophysiol. 82, 301–311 (1999)

    CAS  Article  Google Scholar 

  30. DeAngelis, G. C., Ghose, G. M., Ohzawa, I. & Freeman, R. D. Functional micro-organization of primary visual cortex: receptive field analysis of nearby neurons. J. Neurosci. 19, 4046–4064 (1999)

    CAS  Article  Google Scholar 

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Acknowledgements

We are grateful for support from the National Institutes of Health. We thank Y. Komatsu and F. Briggs and members of the Callaway laboratory for discussions.

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Correspondence to Edward M. Callaway.

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The authors declare that they have no competing financial interests.

Supplementary information

Figure S1

Spatial resolution of photostimulation. (DOC 71 kb)

Figure S2

Timing of action potentials evoked by photostimulation. (DOC 111 kb)

Supplementary Data (DOC 31 kb)

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Yoshimura, Y., Dantzker, J. & Callaway, E. Excitatory cortical neurons form fine-scale functional networks. Nature 433, 868–873 (2005). https://doi.org/10.1038/nature03252

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