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The corticothalamocortical circuit drives higher-order cortex in the mouse

Nature Neuroscience volume 13, pages 84–88 (2010)Cite this article

Abstract

An unresolved question in neuroscience relates to the extent to which corticothalamocortical circuits emanating from layer 5B are involved in information transfer through the cortical hierarchy. Using a new form of optical imaging in a brain slice preparation, we found that the corticothalamocortical pathway drove robust activity in higher-order somatosensory cortex. When the direct corticocortical pathway was interrupted, secondary somatosensory cortex showed robust activity in response to stimulation of the barrel field in primary somatosensory cortex (S1BF), which was eliminated after subsequently cutting the somatosensory thalamus, suggesting a highly efficacious corticothalamocortical circuit. Furthermore, after chemically inhibiting the thalamus, activation in secondary somatosensory cortex was eliminated, with a subsequent return after washout. Finally, stimulation of layer 5B in S1BF, and not layer 6, drove corticothalamocortical activation. These findings suggest that the corticothalamocortical circuit is a physiologically viable candidate for information transfer to higher-order cortical areas.

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Figure 1: Line drawing of the corticothalamocortical circuit.
Figure 2: Demonstration of corticothalamocortical pathway sufficiency to drive secondary somatosensory cortex activity: electrical stimulation.
Figure 3: Demonstration of corticothalamocortical pathway sufficiency to drive secondary somatosensory cortex activity: reversible inactivation.
Figure 4: Simultaneous flavoprotein autofluorescence imaging and whole-cell recording in secondary somatosensory cortex.

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Acknowledgements

We thank N. Issa, T. Husson and A. Mallik for technical assistance with flavoprotein autofluorescence imaging. This work was supported by the US Public Health Service and US National Institutes of Health grants DC008320 (D.A.L.), EY03038 and DC008794 (S.M.S.).

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Author notes

  1. Daniel A Llano

    Present address: Present address: Abbott Laboratories, Abbott Park, Illinois, USA.,

Authors and Affiliations

  1. Department of Neurobiology, University of Chicago, Chicago, Illinois, USA

    Brian B Theyel & S Murray Sherman

  2. Department of Neurology, University of Chicago Medical Center, Chicago, Illinois, USA

    Daniel A Llano

Authors
  1. Brian B Theyel
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Contributions

B.B.T. performed all of the experimental manipulations and data analysis. All authors contributed to hypothesis development, experimental design, data interpretation and manuscript preparation.

Corresponding author

Correspondence to Brian B Theyel.

Supplementary information

Supplementary Text and Figures

Supplementary Figure 1 (PDF 63 kb)

Supplementary Video 1

Demonstration of corticothalamocortical pathway sufficiency to drive activity in secondary somatosensory cortex: electrical stimulation movie. Frames are δF/F (change in fluorescence/baseline fluorescence) images overlaid on top of raw images for anatomy. The first section shows the response in secondary somatosensory cortex to S1BF stimulation in a somatosensory slice preparation. The second section shows the secondary somatosensory cortex response following a cut between S1BF and secondary somatosensory cortex, which likely eliminated the direct pathway. The third section shows cortical response following thalamic ablation. Each stimulus is repeated in each section for emphasis. Time(s) is shown in each frame; movie is approximately 3× real-time. See Figure 2 for more details (MOV 5516 kb)

Supplementary Video 2

Demonstration of corticothalamocortical pathway sufficiency to drive activity in secondary somatosensory cortex: reversible inactivation movie. The first section shows layer 5 of S1BF in an intact corticothalamocortical slice being stimulated via microspritzing of glutamate. The second section shows the slice response to the same stimulus type ~4 minutes after local application of 500 μM DNQX in the thalamic hotspot. The third section shows the response after DNQX washout. See Supplementary Figure 1 and Figure 3 for more details. (MOV 5417 kb)

Supplementary Video 3

Fluorescent tracer injection movie. Lysine-fixable 10,000 MW Texas Red dextran (Invitrogen/Molecular Probes) was injected using the same protocol used to inject DNQX (see Online Methods). The tracer stream is mostly confined to a narrow channel throughout the injection, with only small wisps that track around the interface between the electrode and ACSF but do not approach S1BF or secondary somatosensory cortex. Images were captured using the same equipment under the same conditions used in FA imaging (see Online Methods). Time(s) is shown in each frame; movie is approximately 23.4× real-time. (MOV 3096 kb)

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Theyel, B., Llano, D. & Sherman, S. The corticothalamocortical circuit drives higher-order cortex in the mouse. Nat Neurosci 13, 84–88 (2010). https://doi.org/10.1038/nn.2449

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