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Top-down laminar organization of the excitatory network in motor cortex

Abstract

Cortical layering is a hallmark of the mammalian neocortex and a major determinant of local synaptic circuit organization in sensory systems. In motor cortex, the laminar organization of cortical circuits has not been resolved, although their input-output operations are crucial for motor control. Here, we developed a general approach for estimating layer-specific connectivity in cortical circuits and applied it to mouse motor cortex. From these data we computed a laminar presynaptic → postsynaptic connectivity matrix, Wpost,pre, revealing a complement of stereotypic pathways dominated by layer 2 outflow to deeper layers. Network modeling predicted, and experiments with disinhibited slices confirmed, that stimuli targeting upper, but not lower, cortical layers effectively evoked network-wide events. Thus, in motor cortex, descending excitation from a preamplifier-like network of upper-layer neurons drives output neurons in lower layers. Our analysis provides a quantitative wiring-diagram framework for further investigation of the excitatory networks mediating cortical mechanisms of motor control.

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Figure 1: Experimental approach.
Figure 2: Synaptic input and output in the local circuit.
Figure 3: Network activity in simulated circuits and disinhibited slices.
Figure 4: Wiring diagrams.

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References

  1. Wise, S.P. & Donoghue, J.P. Motor cortex of rodents. in Cerebral Cortex: Sensory-Motor Areas and Aspects of Cortical Connectivity (eds. Jones, E. G. & Peters, A.) 243–270 (Plenum, New York, 1986).

  2. Keller, A. Intrinsic synaptic organization of the motor cortex. Cereb. Cortex 3, 430–441 (1993).

    Article  CAS  Google Scholar 

  3. Schieber, M.H. Constraints on somatotopic organization in the primary motor cortex. J. Neurophysiol. 86, 2125–2143 (2001).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  5. Douglas, R.J. & Martin, K.A. Neuronal circuits of the neocortex. Annu. Rev. Neurosci. 27, 419–451 (2004).

    Article  CAS  Google Scholar 

  6. Silberberg, G., Grillner, S., LeBeau, F.E., Maex, R. & Markram, H. Synaptic pathways in neural microcircuits. Trends Neurosci. 28, 541–551 (2005).

    Article  CAS  Google Scholar 

  7. Alloway, K.D. Information processing streams in rodent barrel cortex: the differential functions of barrel and septal circuits. Cereb. Cortex published online, doi:10.1093/cercor/bhm138 (16 August 2007).

  8. Lübke, J. & Feldmeyer, D. Excitatory signal flow and connectivity in a cortical column: focus on barrel cortex. Brain Struct. Funct. 212, 3–17 (2007).

    Article  Google Scholar 

  9. Schubert, D., Kötter, R. & Staiger, J.F. Mapping functional connectivity in barrel-related columns reveals layer- and cell type–specific microcircuits. Brain Struct. Funct. 212, 107–119 (2007).

    Article  Google Scholar 

  10. Thomson, A.M. & Lamy, C. Functional maps of neocortical local circuitry. Front. Neurosci. 1, 19–42 (2007).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  12. Shepherd, G.M.G. & Svoboda, K. Laminar and columnar organization of ascending excitatory projections to layer 2/3 pyramidal neurons in rat barrel cortex. J. Neurosci. 25, 5670–5679 (2005).

    Article  CAS  Google Scholar 

  13. Bureau, I., von Saint Paul, F. & Svoboda, K. Interdigitated paralemniscal and lemniscal pathways in the mouse barrel cortex. PLoS Biol. 4, e382 (2006).

    Article  Google Scholar 

  14. Kaneko, T., Caria, M.A. & Asanuma, H. Information processing within the motor cortex. II. Intracortical connections between neurons receiving somatosensory cortical input and motor output neurons of the cortex. J. Comp. Neurol. 345, 172–184 (1994).

    Article  CAS  Google Scholar 

  15. Kaneko, T., Cho, R., Li, Y., Nomura, S. & Mizuno, N. Predominant information transfer from layer III pyramidal neurons to corticospinal neurons. J. Comp. Neurol. 423, 52–65 (2000).

    Article  CAS  Google Scholar 

  16. Caviness, V.S., Jr. Architectonic map of neocortex of the normal mouse. J. Comp. Neurol. 164, 247–263 (1975).

    Article  Google Scholar 

  17. Brecht, M. et al. Organization of rat vibrissa motor cortex and adjacent areas according to cytoarchitectonics, microstimulation, and intracellular stimulation of identified cells. J. Comp. Neurol. 479, 360–373 (2004).

    Article  Google Scholar 

  18. 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, e1 (2005).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  20. Shepherd, G.M.G., Stepanyants, A., Bureau, I., Chklovskii, D.B. & Svoboda, K. Geometric and functional organization of cortical circuits. Nat. Neurosci. 8, 782–790 (2005).

    Article  CAS  Google Scholar 

  21. Lehky, S.R. & Sejnowski, T.J. Network model of shape-from-shading: neural function arises from both receptive and projective fields. Nature 333, 452–454 (1988).

    Article  CAS  Google Scholar 

  22. Callaway, E.M. Feedforward, feedback and inhibitory connections in primate visual cortex. Neural Netw. 17, 625–632 (2004).

    Article  Google Scholar 

  23. Connors, B.W. Initiation of synchronized neuronal bursting in neocortex. Nature 310, 685–687 (1984).

    Article  CAS  Google Scholar 

  24. Chagnac-Amitai, Y. & Connors, B.W. Synchronized excitation and inhibition driven by intrinsically bursting neurons in neocortex. J. Neurophysiol. 62, 1149–1162 (1989).

    Article  CAS  Google Scholar 

  25. Crick, F. & Koch, C. Constraints on cortical and thalamic projections: the no-strong-loops hypothesis. Nature 391, 245–250 (1998).

    Article  CAS  Google Scholar 

  26. Strick, P.L. & Sterling, P. Synaptic termination of afferents from the ventrolateral nucleus of the thalamus in the cat motor cortex. A light and electron microscopy study. J. Comp. Neurol. 153, 77–106 (1974).

    Article  CAS  Google Scholar 

  27. Jones, E.G. Lamination and differential distribution of thalamic afferents within the sensory-motor cortex of the squirrel monkey. J. Comp. Neurol. 160, 167–203 (1975).

    Article  CAS  Google Scholar 

  28. Nelson, S. Cortical microcircuits: diverse or canonical? Neuron 36, 19–27 (2002).

    Article  CAS  Google Scholar 

  29. Fregnac, Y. et al. The interface between neurons and global brain function. in Microcircuits (eds. Grillner, S. & Graybiel, A. M.) 393–433 (MIT Press, Cambridge, Massachusetts, 2006).

    Google Scholar 

  30. Ohki, K. & Reid, R.C. Specificity and randomness in the visual cortex. Curr. Opin. Neurobiol. 17, 401–407 (2007).

    Article  CAS  Google Scholar 

  31. 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).

    Article  CAS  Google Scholar 

  32. Stepanyants, A. et al. Local potential connectivity in cat primary visual cortex. Cereb. Cortex 18, 13–28 (2008).

    Article  Google Scholar 

  33. Lübke, J., Roth, A., Feldmeyer, D. & Sakmann, B. Morphometric analysis of the columnar innervation domain of neurons connecting layer 4 and layer 2/3 of juvenile rat barrel cortex. Cereb. Cortex 13, 1051–1063 (2003).

    Article  Google Scholar 

  34. Helmstaedter, M., de Kock, C.P., Feldmeyer, D., Bruno, R.M. & Sakmann, B. Reconstruction of an average cortical column in silico. Brain Res. Rev. 55, 193–203 (2007).

    Article  CAS  Google Scholar 

  35. Braitenberg, V.B. & Schüz, A. Cortex: Statistics and Geometry of Neuronal Connectivity (Springer, Berlin, 1998).

  36. Stepanyants, A. & Chklovskii, D.B. Neurogeometry and potential synaptic connectivity. Trends Neurosci. 28, 387–394 (2005).

    Article  CAS  Google Scholar 

  37. Armstrong-James, M., Fox, K. & Das-Gupta, A. Flow of excitation within rat barrel cortex on striking a single vibrissa. J. Neurophysiol. 68, 1345–1358 (1992).

    Article  CAS  Google Scholar 

  38. Schubert, D., Kötter, 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).

    Article  CAS  Google Scholar 

  39. Kaneko, T., Kang, Y. & Mizuno, N. Glutaminase-positive and glutaminase-negative pyramidal cells in layer VI of the primary motor and somatosensory cortices: a combined analysis by intracellular staining and immunocytochemistry in the rat. J. Neurosci. 15, 8362–8377 (1995).

    Article  CAS  Google Scholar 

  40. Hirsch, J.A. Synaptic integration in layer 4 of the ferret striate cortex. J. Physiol. (Lond.) 483, 183–199 (1995).

    Article  CAS  Google Scholar 

  41. Zhang, Z.W. & Deschenes, M. Intracortical axonal projections of lamina VI cells of the primary somatosensory cortex in the rat: a single-cell labeling study. J. Neurosci. 17, 6365–6379 (1997).

    Article  CAS  Google Scholar 

  42. Tarczy-Hornoch, K., Martin, K.A., Stratford, K.J. & Jack, J.J. Intracortical excitation of spiny neurons in layer 4 of cat striate cortex in vitro. Cereb. Cortex 9, 833–843 (1999).

    Article  CAS  Google Scholar 

  43. Briggs, F. & Callaway, E.M. Laminar patterns of local excitatory input to layer 5 neurons in macaque primary visual cortex. Cereb. Cortex 15, 479–488 (2005).

    Article  Google Scholar 

  44. Petreanu, L., Huber, D., Sobczyk, A. & Svoboda, K. Channelrhodopsin 2–assisted circuit mapping of long-range callosal projections. Nat. Neurosci. 10, 663–668 (2007).

    Article  CAS  Google Scholar 

  45. Schubert, D. et al. Layer-specific intracolumnar and transcolumnar functional connectivity of layer V pyramidal cells in rat barrel cortex. J. Neurosci. 21, 3580–3592 (2001).

    Article  CAS  Google Scholar 

  46. Shipp, S. The importance of being agranular: a comparative account of visual and motor cortex. Phil. Trans. R. Soc. Lond. B 360, 797–814 (2005).

    Article  Google Scholar 

  47. Llinás, R. I of the Vortex: From Neurons to Self (M.I.T. Press, Cambridge, Massachusetts, 2002).

  48. Huber, D. et al. Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice. Nature 451, 61–64 (2007).

    Article  Google Scholar 

  49. Castro-Alamancos, M.A. Origin of synchronized oscillations induced by neocortical disinhibition in vivo. J. Neurosci. 20, 9195–9206 (2000).

    Article  CAS  Google Scholar 

  50. Pouille, F. & Scanziani, M. Routing of spike series by dynamic circuits in the hippocampus. Nature 429, 717–723 (2004).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank W. Kath, A. Stepanyants, K. Svoboda, M. Tresch, and J. Waters for comments and suggestions. We appreciate funding support provided through grants from the Whitehall Foundation, Simons Foundation and Rett Syndrome Research Foundation (G.M.G.S.).

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Contributions

Experiments were conducted by N.W., L.W., J.Y. and G.M.G.S., and simulations by S.A.S. and G.M.G.S. All authors participated in data analysis and interpretation. G.M.G.S. supervised the project and drafted the manuscript.

Corresponding author

Correspondence to Gordon M G Shepherd.

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The authors declare no competing financial interests.

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Weiler, N., Wood, L., Yu, J. et al. Top-down laminar organization of the excitatory network in motor cortex. Nat Neurosci 11, 360–366 (2008). https://doi.org/10.1038/nn2049

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