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Gain control by layer six in cortical circuits of vision

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Abstract

After entering the cerebral cortex, sensory information spreads through six different horizontal neuronal layers that are interconnected by vertical axonal projections. It is believed that through these projections layers can influence each other's response to sensory stimuli, but the specific role that each layer has in cortical processing is still poorly understood. Here we show that layer six in the primary visual cortex of the mouse has a crucial role in controlling the gain of visually evoked activity in neurons of the upper layers without changing their tuning to orientation. This gain modulation results from the coordinated action of layer six intracortical projections to superficial layers and deep projections to the thalamus, with a substantial role of the intracortical circuit. This study establishes layer six as a major mediator of cortical gain modulation and suggests that it could be a node through which convergent inputs from several brain areas can regulate the earliest steps of cortical visual processing.

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Figure 1: Photostimulation of L6 suppresses visual responses in the other layers.
Figure 2: L6 bidirectionally modulates the gain of visual responses without altering tuning.
Figure 3: Photostimulation of L6 suppresses cortex faster than it suppresses dLGN.
Figure 4: Photostimulation of L6 recruits intracortical synaptic inhibition.
Figure 5: L6 suppresses upper layers largely through intracortical circuits.

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Acknowledgements

We are grateful to M. Carandini, J. Isaacson and the members of the Scanziani and Isaacson laboratories for helpful discussions of this project, to J. Isaacson, R. Malinow and T. Komiyama for providing feedback on the manuscript, to P. Abelkop for histological help and neonatal viral injections, to J. Evora for mouse colony support and genotyping, to B. Atallah for sharing the technique for silencing the cortex by photostimulation of parvalbumin neurons and for help with the in vivo recording setup and to W. Bruns for help coding analysis software. We thank the UCSD Neuroscience Microscopy Facility (P30 NS047101) for the use of their imaging equipment. S.R.O. and H.A. were supported by postdoctoral fellowships from the Helen Hay Whitney Foundation. D.S.B was supported by a UCSD Neurobiology Training Grant (NINDS: 5T32NS007220-28). M.S. is an investigator of the Howard Hughes Medical Institute. This work was also supported National Institutes of Health grant RO1 NS069010 and by the Gatsby Charitable Foundation.

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H.A. performed the initial physiological characterization of the NTSR1-Cre expression system with optogenetic tools. H.A. also developed the in vivo awake recording preparation on the treadmill. S.R.O. performed all in vivo recordings. D.S.B. performed all in vitro recordings and anatomical reconstructions. S.R.O. and M.S. designed the study. M.S. wrote the paper.

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Correspondence to Shawn R. Olsen or Massimo Scanziani.

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Olsen, S., Bortone, D., Adesnik, H. et al. Gain control by layer six in cortical circuits of vision. Nature 483, 47–52 (2012). https://doi.org/10.1038/nature10835

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