Linear transformation of thalamocortical input by intracortical excitation



Neurons in thalamorecipient layers of sensory cortices integrate thalamocortical and intracortical inputs. Although we know that their functional properties can arise from the convergence of thalamic inputs, intracortical circuits could also be involved in thalamocortical transformations of sensory information. We silenced intracortical excitatory circuits with optogenetic activation of parvalbumin-positive inhibitory neurons in mouse primary visual cortex and compared visually evoked thalamocortical input with total excitation in the same layer 4 pyramidal neurons. We found that intracortical excitatory circuits preserved the orientation and direction tuning of thalamocortical excitation, with a linear amplification of thalamocortical signals of about threefold. The spatial receptive field of thalamocortical input was slightly elongated and was expanded by intracortical excitation in an approximately proportional manner. Thus, intracortical excitatory circuits faithfully reinforce the representation of thalamocortical information and may influence the size of the receptive field by recruiting additional inputs.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Optogenetic silencing of visual cortical circuits.
Figure 2: Linear amplification of orientation-tuned thalamocortical input.
Figure 3: Intracortical excitation preserves direction tuning.
Figure 4: Intracortical excitation expands visual receptive field.
Figure 5: Orientation tuning of thalamic neurons.


  1. 1

    Douglas, R.J. & Martin, K.A. A functional microcircuit for cat visual cortex. J. Physiol. (Lond.) 440, 735–769 (1991).

  2. 2

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

  3. 3

    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).

  4. 4

    Reid, R.C. & Alonso, J.M. Specificity of monosynaptic connections from thalamus to visual cortex. Nature 378, 281–284 (1995).

  5. 5

    Lampl, I., Anderson, J.S., Gillespie, D.C. & Ferster, D. Prediction of orientation selectivity from receptive field architecture in simple cells of cat visual cortex. Neuron 30, 263–274 (2001).

  6. 6

    Ferster, D. & Miller, K.D. Neural mechanisms of orientation selectivity in the visual cortex. Annu. Rev. Neurosci. 23, 441–471 (2000).

  7. 7

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

  8. 8

    Chung, S. & Ferster, D. Strength and orientation tuning of the thalamic input to simple cells revealed by electrically evoked cortical suppression. Neuron 20, 1177–1189 (1998).

  9. 9

    Ben-Yishai, R., Bar-Or, R.L. & Sompolinsky, H. Theory of orientation tuning in visual cortex. Proc. Natl. Acad. Sci. USA 92, 3844–3848 (1995).

  10. 10

    Somers, D.C., Nelson, S.B. & Sur, M. An emergent model of orientation selectivity in cat visual cortical simple cells. J. Neurosci. 15, 5448–5465 (1995).

  11. 11

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

  12. 12

    Ben-Yishai, R., Hansel, D. & Sompolinsky, H. Traveling waves and the processing of weakly tuned inputs in a cortical network module. J. Comput. Neurosci. 4, 57–77 (1997).

  13. 13

    Adorján, P., Levitt, J.B., Lund, J.S. & Obermayer, K. A model for the intracortical origin of orientation preference and tuning in macaque striate cortex. Vis. Neurosci. 16, 303–318 (1999).

  14. 14

    McLaughlin, D., Shapley, R., Shelley, M. & Wielaard, D.J. A neuronal network model of macaque primary visual cortex (V1): orientation selectivity and dynamics in the input layer 4Calpha. Proc. Natl. Acad. Sci. USA 97, 8087–8092 (2000).

  15. 15

    Liu, B.H., Wu, G.K., Arbuckle, R., Tao, H.W. & Zhang, L.I. Defining cortical frequency tuning with recurrent excitatory circuitry. Nat. Neurosci. 10, 1594–1600 (2007).

  16. 16

    Khibnik, L.A., Cho, K.K. & Bear, M.F. Relative contribution of feedforward excitatory connections to expression of ocular dominance plasticity in layer 4 of visual cortex. Neuron 66, 493–500 (2010).

  17. 17

    Yamauchi, T., Hori, T. & Takahashi, T. Presynaptic inhibition by muscimol through GABAB receptors. Eur. J. Neurosci. 12, 3433–3436 (2000).

  18. 18

    Porter, J.T. & Nieves, D. Presynaptic GABAB receptors modulate thalamic excitation of inhibitory and excitatory neurons in the mouse barrel cortex. J. Neurophysiol. 92, 2762–2770 (2004).

  19. 19

    Zhang, F., Aravanis, A.M., Adamantidis, A., de Lecea, L. & Deisseroth, K. Circuit-breakers: optical technologies for probing neural signals and systems. Nat. Rev. Neurosci. 8, 577–581 (2007).

  20. 20

    Bernstein, J.G., Garrity, P.A. & Boyden, E.S. Optogenetics and thermogenetics: technologies for controlling the activity of targeted cells within intact neural circuits. Curr. Opin. Neurobiol. 22, 61–71 (2012).

  21. 21

    Olsen, S.R., Bortone, D.S., Adesnik, H. & Scanziani, M. Gain control by layer six in cortical circuits of vision. Nature 483, 47–52 (2012).

  22. 22

    Ma, W.P. et al. Visual representations by cortical somatostatin inhibitory neurons—selective, but with weak and delayed responses. J. Neurosci. 30, 14371–14379 (2010).

  23. 23

    Liu, B.H. et al. Visual receptive field structure of cortical inhibitory neurons revealed by two-photon imaging guided recording. J. Neurosci. 29, 10520–10532 (2009).

  24. 24

    Katzner, S. et al. Local origin of field potentials in visual cortex. Neuron 61, 35–41 (2009).

  25. 25

    Pfrieger, F.W., Gottmann, K. & Lux, H.D. Kinetics of GABAB receptor–mediated inhibition of calcium currents and excitatory synaptic transmission in hippocampal neurons in vitro. Neuron 12, 97–107 (1994).

  26. 26

    Niell, C.M. & Stryker, M.P. Highly selective receptive fields in mouse visual cortex. J. Neurosci. 28, 7520–7536 (2008).

  27. 27

    Priebe, N.J. & Ferster, D. Inhibition, spike threshold, and stimulus selectivity in primary visual cortex. Neuron 57, 482–497 (2008).

  28. 28

    Volgushev, M., Vidyasagar, T.R. & Pei, X. A linear model fails to predict orientation selectivity of cells in the cat visual cortex. J. Physiol. (Lond.) 496, 597–606 (1996).

  29. 29

    Cruikshank, S.J., Urabe, H., Nurmikko, A.V. & Connors, B.W. Pathway-specific feedforward circuits between thalamus and neocortex revealed by selective optical stimulation of axons. Neuron 65, 230–245 (2010).

  30. 30

    Piscopo, D.M., El-Danaf, R.N., Huberman, A.D. & Niell, C.M. Diverse visual features encoded in mouse lateral geniculate nucleus. J. Neurosci. 33, 4642–4656 (2013).

  31. 31

    Bruno, R.M. & Sakmann, B. Cortex is driven by weak but synchronously active thalamocortical synapses. Science 312, 1622–1627 (2006).

  32. 32

    Jin, J., Wang, Y., Swadlow, H.A. & Alonso, J.M. Population receptive fields of ON and OFF thalamic inputs to an orientation column in visual cortex. Nat. Neurosci. 14, 232–238 (2011).

  33. 33

    Kerlin, A.M., Andermann, M.L., Berezovskii, V.K. & Reid, R.C. Broadly tuned response properties of diverse inhibitory neuron subtypes in mouse visual cortex. Neuron 67, 858–871 (2010).

  34. 34

    Ko, H. et al. Functional specificity of local synaptic connections in neocortical networks. Nature 473, 87–91 (2011).

  35. 35

    Liu, B.H. et al. Broad inhibition sharpens orientation selectivity by expanding input dynamic range in mouse simple cells. Neuron 71, 542–554 (2011).

  36. 36

    Li, Y.T. et al. Broadening of inhibitory tuning underlies contrast-dependent sharpening of orientation selectivity in mouse visual cortex. J. Neurosci. 32, 16466–16477 (2012).

  37. 37

    Atallah, B.V., Bruns, W., Carandini, M. & Scanziani, M. Parvalbumin-expressing interneurons linearly transform cortical responses to visual stimuli. Neuron 73, 159–170 (2012).

  38. 38

    Wilson, N.R., Runyan, C.A., Wang, F.L. & Sur, M. Division and subtraction by distinct cortical inhibitory networks in vivo. Nature 488, 343–348 (2012).

  39. 39

    Lee, S.H. et al. Activation of specific interneurons improves V1 feature selectivity and visual perception. Nature 488, 379–383 (2012).

  40. 40

    Liu, B.H. et al. Intervening inhibition underlies simple-cell receptive field structure in visual cortex. Nat. Neurosci. 13, 89–96 (2010).

  41. 41

    Tan, A.Y., Brown, B.D., Scholl, B., Mohanty, D. & Priebe, N.J. Orientation selectivity of synaptic input to neurons in mouse and cat primary visual cortex. J. Neurosci. 31, 12339–12350 (2011).

  42. 42

    Katzner, S., Busse, L. & Carandini, M. GABAA inhibition controls response gain in visual cortex. J. Neurosci. 31, 5931–5941 (2011).

  43. 43

    Branco, T., Clark, B.A. & Hausser, M. Dendritic discrimination of temporal input sequences in cortical neurons. Science 329, 1671–1675 (2010).

  44. 44

    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).

  45. 45

    Allman, J., Miezin, F. & McGuinness, E. Stimulus specific responses from beyond the classical receptive field: neurophysiological mechanisms for local-global comparisons in visual neurons. Annu. Rev. Neurosci. 8, 407–430 (1985).

  46. 46

    Gilbert, C.D. & Wiesel, T.N. The influence of contextual stimuli on the orientation selectivity of cells in primary visual cortex of the cat. Vision Res. 30, 1689–1701 (1990).

  47. 47

    Levitt, J.B. & Lund, J.S. Contrast dependence of contextual effects in primate visual cortex. Nature 387, 73–76 (1997).

  48. 48

    Chisum, H.J., Mooser, F. & Fitzpatrick, D. Emergent properties of layer 2/3 neurons reflect the collinear arrangement of horizontal connections in tree shrew visual cortex. J. Neurosci. 23, 2947–2960 (2003).

  49. 49

    Clopath, C., Busing, L., Vasilaki, E. & Gerstner, W. Connectivity reflects coding: a model of voltage-based STDP with homeostasis. Nat. Neurosci. 13, 344–352 (2010).

  50. 50

    Ko, H. et al. The emergence of functional microcircuits in visual cortex. Nature 496, 96–100 (2013).

  51. 51

    Grubb, M.S. & Thompson, I.D. Quantitative characterization of visual response properties in the mouse dorsal lateral geniculate nucleus. J. Neurophysiol. 90, 3594–3607 (2003).

  52. 52

    Lin, J.Y., Lin, M.Z., Steinbach, P. & Tsien, R.Y. Characterization of engineered channelrhodopsin variants with improved properties and kinetics. Biophys. J. 96, 1803–1814 (2009).

  53. 53

    Li, Y.T., Ma, W.P., Pan, C.J., Zhang, L.I. & Tao, H.W. Broadening of cortical inhibition mediates developmental sharpening of orientation selectivity. J. Neurosci. 32, 3981–3991 (2012).

  54. 54

    Wu, G.K., Li, P., Tao, H.W. & Zhang, L.I. Nonmonotonic synaptic excitation and imbalanced inhibition underlying cortical intensity tuning. Neuron 52, 705–715 (2006).

  55. 55

    Petreanu, L., Mao, T., Sternson, S.M. & Svoboda, K. The subcellular organization of neocortical excitatory connections. Nature 457, 1142–1145 (2009).

  56. 56

    Zhang, M. et al. Functional elimination of excitatory feedforward inputs underlies developmental refinement of visual receptive fields in zebrafish. J. Neurosci. 31, 5460–5469 (2011).

  57. 57

    Wehr, M. & Zador, A.M. Balanced inhibition underlies tuning and sharpens spike timing in auditory cortex. Nature 426, 442–446 (2003).

  58. 58

    Wu, G.K., Tao, H.W. & Zhang, L.I. From elementary synaptic circuits to information processing in primary auditory cortex. Neurosci. Biobehav. Rev. 35, 2094–2104 (2011).

  59. 59

    Tan, A.Y., Zhang, L.I., Merzenich, M.M. & Schreiner, C.E. Tone-evoked excitatory and inhibitory synaptic conductances of primary auditory cortex neurons. J. Neurophysiol. 92, 630–643 (2004).

Download references


We thank M. Scanziani for the help on viral injection setup. This work was supported by grants to H.W.T. from the US National Institutes of Health (EY019049 and EY022478) and the Kirchgessner Foundation.

Author information

H.W.T. conceived and designed the study. Y.L. and L.A.I. performed the experiment. Y.L. and L.I.Z. performed data analysis. B.L. contributed data on direction tuning. H.W.T. wrote the paper.

Correspondence to Huizhong Whit Tao.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–4 (PDF 273 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Li, Y., Ibrahim, L., Liu, B. et al. Linear transformation of thalamocortical input by intracortical excitation. Nat Neurosci 16, 1324–1330 (2013) doi:10.1038/nn.3494

Download citation

Further reading