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Division and subtraction by distinct cortical inhibitory networks in vivo


Brain circuits process information through specialized neuronal subclasses interacting within a network. Revealing their interplay requires activating specific cells while monitoring others in a functioning circuit. Here we use a new platform for two-way light-based circuit interrogation in visual cortex in vivo to show the computational implications of modulating different subclasses of inhibitory neurons during sensory processing. We find that soma-targeting, parvalbumin-expressing (PV) neurons principally divide responses but preserve stimulus selectivity, whereas dendrite-targeting, somatostatin-expressing (SOM) neurons principally subtract from excitatory responses and sharpen selectivity. Visualized in vivo cell-attached recordings show that division by PV neurons alters response gain, whereas subtraction by SOM neurons shifts response levels. Finally, stimulating identified neurons while scanning many target cells reveals that single PV and SOM neurons functionally impact only specific subsets of neurons in their projection fields. These findings provide direct evidence that inhibitory neuronal subclasses have distinct and complementary roles in cortical computations.

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Figure 1: All-optical network dissection of cortical subclasses during visual computations.
Figure 2: Impact of PV- and SOM-driven inhibition on the tuning of neuronal responses.
Figure 3: Electrophysiological analysis of PV- and SOM-driven inhibition.
Figure 4: Modulation of response gain by PV and SOM cells during targeted cell-attached recordings.
Figure 5: Dual-laser optical mapping of network connections to reveal maps of functional inhibition by single PV and SOM neurons.
Figure 6: Spatial and functional analysis of targeting by single PV and SOM neurons.


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We thank J. Huang for providing the SOM–Cre mouse line; C. Le for performing animal care support and viral injections; S. Yan and Y. Deng for help in the development of optogenetics and imaging methods in vitro; S. El-Boustani for collecting data for in vivo deconvolution; J. Sharma, M. Goard and A. Banerjee for comments and discussions on the manuscript; L.-H. Tsai, K. Meletis and M. Carlen for early provision of viral constructs and PV–Cre viral injections; and James Schummers and Hiroki Sugihara for participating in early pilot experiments testing optogenetics stimulation in vivo. This work was supported by postdoctoral fellowships from the US National Institutes of Health (NIH) and the Simons Foundation (N.R.W.), an NIH predoctoral fellowship (C.A.R.) and grants from the NIH and the Simons Foundation (M.S.).

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Authors and Affiliations



Author Contributions N.R.W. conceived experiments, designed and engineered circuit interface and analysis systems, carried out in vivo and in vitro experiments, and performed analyses. C.A.R. conceived experiments, performed surgeries and viral injections, carried out in vivo experiments, and performed analyses. F.L.W. carried out in vivo experiments, and performed analyses. M.S. conceived experiments and contributed to analysis of experiments. N.R.W., C.A.R. and M.S. wrote the paper.

Corresponding authors

Correspondence to Nathan R. Wilson or Mriganka Sur.

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Supplementary information

Supplementary Information

This file contains Supplementary Methods and additional references, Supplementary Figures 1-21 and full legends for Supplementary Movies 1-4. (PDF 7930 kb)

Supplementary Movie 1

This file contains a movie showing increased dwell time in cells during two-photon imaging via targeted scan imaging (see Supplementary Information file for full legend). (MOV 15157 kb)

Supplementary Movie 2

This file contains a movie showing targeted scanning of identified cells responding to visual stimuli (see Supplementary Information file for full legend). (MOV 4567 kb)

Supplementary Movie 3

This file contains a movie showing targeted scanning combined with full-field optogenetic stimulation (see Supplementary Information file for full legend). (MOV 5211 kb)

Supplementary Movie 4

This file contains a movie showing targeted scanning combined with single-cell optogenetic stimulation (see Supplementary Information file for full legend). (MOV 5034 kb)

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Wilson, N., Runyan, C., Wang, F. et al. Division and subtraction by distinct cortical inhibitory networks in vivo. Nature 488, 343–348 (2012).

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