Intracortical circuits of pyramidal neurons reflect their long-range axonal targets

Abstract

Cortical columns generate separate streams of information that are distributed to numerous cortical and subcortical brain regions1. We asked whether local intracortical circuits reflect these different processing streams by testing whether the intracortical connectivity among pyramidal neurons reflects their long-range axonal targets. We recorded simultaneously from up to four retrogradely labelled pyramidal neurons that projected to the superior colliculus, the contralateral striatum or the contralateral cortex to assess their synaptic connectivity. Here we show that the probability of synaptic connection depends on the functional identities of both the presynaptic and postsynaptic neurons. We first found that the frequency of monosynaptic connections among corticostriatal pyramidal neurons is significantly higher than among corticocortical or corticotectal pyramidal neurons. We then show that the probability of feed-forward connections from corticocortical neurons to corticotectal neurons is approximately three- to fourfold higher than the probability of monosynaptic connections among corticocortical or corticotectal cells. Moreover, we found that the average axodendritic overlap of the presynaptic and postsynaptic pyramidal neurons could not fully explain the differences in connection probability that we observed. The selective synaptic interactions we describe demonstrate that the organization of local networks of pyramidal cells reflects the long-range targets of both the presynaptic and postsynaptic neurons.

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Figure 1: Different frequencies of monosynaptic connections between corticotectal, corticostriatal or corticocortical neurons.
Figure 2: The probability of connection depends on the identities of the presynaptic and the postsynaptic pyramidal cell types.
Figure 3: The average axonal and dendritic architecture alone cannot explain differences in the connection probability.

References

  1. 1

    Jones, E. G. in Cerebral Cortex (eds Peters, A. & Jones, E. G.) 521–553 (Plenum, 1984)

    Google Scholar 

  2. 2

    Kisvarday, Z. F. et al. Synaptic targets of HRP-filled layer III pyramidal cells in the cat striate cortex. Exp. Brain Res. 64, 541–552 (1986)

    CAS  Article  Google Scholar 

  3. 3

    McGuire, B. A., Hornung, J. P., Gilbert, C. D. & Wiesel, T. N. Patterns of synaptic input to layer 4 of cat striate cortex. J. Neurosci. 4, 3021–3033 (1984)

    CAS  Article  Google Scholar 

  4. 4

    Braitenberg, V. & Schuz, A. Cortex: Statistics and Geometry of Neuronal Connectivity (Springer, 1998)

    Google Scholar 

  5. 5

    Kozloski, J., Hamzei-Sichani, F. & Yuste, R. Stereotyped position of local synaptic targets in neocortex. Science 293, 868–872 (2001)

    CAS  Article  Google Scholar 

  6. 6

    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)

    Article  Google Scholar 

  7. 7

    Wang, Y. et al. Heterogeneity in the pyramidal network of the medial prefrontal cortex. Nature Neurosci. 9, 534–542 (2006)

    ADS  CAS  Article  Google Scholar 

  8. 8

    Kampa, B. M., Letzkus, J. J. & Stuart, G. J. Cortical feed-forward networks for binding different streams of sensory information. Nature Neurosci. 9, 1472–1473 (2006)

    CAS  Article  Google Scholar 

  9. 9

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

    ADS  CAS  Article  Google Scholar 

  10. 10

    Le Bé, J. V., Silberberg, G., Wang, Y. & Markram, H. Morphological, electrophysiological, and synaptic properties of corticocallosal pyramidal cells in the neonatal rat neocortex. Cereb. Cortex 17, 2204–2213 (2006)

    Article  Google Scholar 

  11. 11

    Morishima, M. & Kawaguchi, Y. Recurrent connection patterns of corticostriatal pyramidal cells in frontal cortex. J. Neurosci. 26, 4394–4405 (2006)

    CAS  Article  Google Scholar 

  12. 12

    Kasper, E. M., Larkman, A. U., Lubke, J. & Blakemore, C. Pyramidal neurons in layer 5 of the rat visual cortex. I. Correlation among cell morphology, intrinsic electrophysiological properties, and axon targets. J. Comp. Neurol. 339, 459–474 (1994)

    CAS  Article  Google Scholar 

  13. 13

    Wang, Z. & McCormick, D. A. Control of firing mode of corticotectal and corticopontine layer V burst-generating neurons by norepinephrine, acetylcholine, and 1S,3R-ACPD. J. Neurosci. 13, 2199–2216 (1993)

    CAS  Article  Google Scholar 

  14. 14

    Hattox, A. M. & Nelson, S. B. Layer V neurons in mouse cortex projecting to different targets have distinct physiological properties. J. Neurophysiol. 98, 3330–3340 (2007)

    Article  Google Scholar 

  15. 15

    Markram, H., Lubke, J., Frotscher, M., Roth, A. & Sakmann, B. Physiology and anatomy of synaptic connections between thick tufted pyramidal neurones in the developing rat neocortex. J. Physiol. (Lond.) 500, 409–440 (1997)

    CAS  Article  Google Scholar 

  16. 16

    Thomson, A. M., Deuchars, J. & West, D. C. Large, deep layer pyramid-pyramid single axon EPSPs in slices of rat motor cortex display paired pulse and frequency-dependent depression, mediated presynaptically and self-facilitation, mediated postsynaptically. J. Neurophysiol. 70, 2354–2369 (1993)

    CAS  Article  Google Scholar 

  17. 17

    Mercer, A. et al. Excitatory connections made by presynaptic cortico-cortical pyramidal cells in layer 6 of the neocortex. Cereb. Cortex 15, 1485–1496 (2005)

    Article  Google Scholar 

  18. 18

    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 

  19. 19

    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 

  20. 20

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

    CAS  Article  Google Scholar 

  21. 21

    Kalisman, N., Silberberg, G. & Markram, H. Deriving physical connectivity from neuronal morphology. Biol. Cybern. 88, 210–218 (2003)

    Article  Google Scholar 

  22. 22

    Hallman, L. E., Schofield, B. R. & Lin, C. S. Dendritic morphology and axon collaterals of corticotectal, corticopontine, and callosal neurons in layer V of primary visual cortex of the hooded rat. J. Comp. Neurol. 272, 149–160 (1988)

    CAS  Article  Google Scholar 

  23. 23

    Hubener, M. & Bolz, J. Morphology of identified projection neurons in layer 5 of rat visual cortex. Neurosci. Lett. 94, 76–81 (1988)

    CAS  Article  Google Scholar 

  24. 24

    Larsen, D. D., Wickersham, I. R. & Callaway, E. M. Retrograde tracing with recombinant rabies virus reveals correlations between projection targets and dendritic architecture in layer 5 of mouse barrel cortex. Front. Neural Circuits 10.3389/neuro.04.005.2007 (2008)

  25. 25

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

    CAS  Article  Google Scholar 

  26. 26

    Frick, A., Feldmeyer, D., Helmstaedter, M. & Sakmann, B. Monosynaptic connections between pairs of L5A pyramidal neurons in columns of juvenile rat somatosensory cortex. Cereb. Cortex 18, 397–406 (2008)

    Article  Google Scholar 

  27. 27

    Stern, E. A., Jaeger, D. & Wilson, C. J. Membrane potential synchrony of simultaneously recorded striatal spiny neurons in vivo . Nature 394, 475–478 (1998)

    ADS  CAS  Article  Google Scholar 

  28. 28

    Douglas, R. J., Koch, C., Mahowald, M., Martin, K. A. & Suarez, H. H. Recurrent excitation in neocortical circuits. Science 269, 981–985 (1995)

    ADS  CAS  Article  Google Scholar 

  29. 29

    Swadlow, H. A. Efferent neurons and suspected interneurons in binocular visual cortex of the awake rabbit: receptive fields and binocular properties. J. Neurophysiol. 59, 1162–1187 (1988)

    CAS  Article  Google Scholar 

  30. 30

    Singer, W., Tretter, F. & Cynader, M. Organization of cat striate cortex: a correlation of receptive-field properties with afferent and efferent connections. J. Neurophysiol. 38, 1080–1098 (1975)

    CAS  Article  Google Scholar 

  31. 31

    Feng, G. et al. Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron 28, 41–51 (2000)

    CAS  Article  Google Scholar 

  32. 32

    Paxinos, G. & Fanklin, K. B. J. The Mouse Brain in Stereotaxic Coordinates (Academic, 2001)

    Google Scholar 

  33. 33

    Katz, L. C., Burkhalter, A. & Dreyer, W. J. Fluorescent latex microspheres as a retrograde neuronal marker for in vivo and in vitro studies of visual cortex. Nature 310, 498–500 (1984)

    ADS  CAS  Article  Google Scholar 

  34. 34

    Wilson, C. J. Morphology and synaptic connections of crossed corticostriatal neurons in the rat. J. Comp. Neurol. 263, 567–580 (1987)

    CAS  Article  Google Scholar 

  35. 35

    Lei, W., Jiao, Y., Del Mar, N. & Reiner, A. Evidence for differential cortical input to direct pathway versus indirect pathway striatal projection neurons in rats. J. Neurosci. 24, 8289–8299 (2004)

    CAS  Article  Google Scholar 

  36. 36

    Reiner, A., Jiao, Y., Del Mar, N., Laverghetta, A. V. & Lei, W. L. Differential morphology of pyramidal tract-type and intratelencephalically projecting-type corticostriatal neurons and their intrastriatal terminals in rats. J. Comp. Neurol. 457, 420–440 (2003)

    Article  Google Scholar 

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Acknowledgements

We thank J. Li and S. Pak for technical assistance. This work was supported by National Institutes of Health grants to S.P.B and to S.H.

Author Contributions S.P.B. and S.H. designed the experiments. S.P.B. collected the data and S.P.B. and S.H. performed the analyses. S.P.B. and S.H. wrote the paper.

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Correspondence to Shaul Hestrin.

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Brown, S., Hestrin, S. Intracortical circuits of pyramidal neurons reflect their long-range axonal targets. Nature 457, 1133–1136 (2009). https://doi.org/10.1038/nature07658

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