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Cellular mechanisms of brain state–dependent gain modulation in visual cortex

Nature Neuroscience volume 16, pages 1331–1339 (2013)Cite this article

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Abstract

Visual cortical neurons fire at higher rates to visual stimuli during locomotion than during immobility, while maintaining orientation selectivity. The mechanisms underlying this change in gain are not understood. We performed whole-cell recordings from layer 2/3 and layer 4 visual cortical excitatory neurons and from parvalbumin-positive and somatostatin-positive inhibitory neurons in mice that were free to rest or run on a spherical treadmill. We found that the membrane potential of all cell types became more depolarized and (with the exception of somatostatin-positive interneurons) less variable during locomotion. Cholinergic input was essential for maintaining the unimodal membrane potential distribution during immobility, whereas noradrenergic input was necessary for the tonic depolarization associated with locomotion. Our results provide a mechanism for how neuromodulation controls the gain and signal-to-noise ratio of visual cortical neurons during changes in the state of vigilance.

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Figure 1: Spontaneous activity of L2/3 neurons during stationary and locomotion periods.
Figure 2: Locomotion is associated with an increase in the gain of L2/3 excitatory neurons.
Figure 3: Effect of locomotion on Vm of L2/3 PV+ interneurons.
Figure 4: Effect of locomotion on the intracellular activity of L2/3 SOM+ interneurons.
Figure 5: L4 neuron signal-to-noise ratio increases during locomotion.
Figure 6: Effect of cholinergic antagonists on the L2/3 neuron Vm during stationary and locomotion periods.
Figure 7: Effect of norepinephrine antagonists on the Vm of L2/3 neurons during stationary and locomotion periods.
Figure 8: Effect of glutamatergic antagonists on the Vm of L2/3 neurons during stationary and locomotion periods.

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Acknowledgements

We acknowledge R. Gruver for technical assistance on visual stimulation, Z. Peng and C. Houser for histology, and D. Contreras, M. Einstein, T. Indersmitten, M. Javaherian, C. Kaba, S. Mahon, A. Silva and S. Singh for their thoughtful comments on the manuscript. This work was supported by the US National Institutes of Health (KO8 NS0562101), the Whitehall Foundation (grant 2012-05-83) and a Veterans Affairs Merit Review Award (1I01BX001524-01A1).

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  1. Department of Neurology, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, California, USA

    Pierre-Olivier Polack, Jonathan Friedman & Peyman Golshani

  2. Department of Neurology, West Los Angeles Veterans Affairs Medical Center, Los Angeles, California, USA

    Pierre-Olivier Polack & Peyman Golshani

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P.-O.P. and P.G. conceived and designed the experiments. P.-O.P., J.F. and P.G. built the experimental setup. P.-O.P. acquired and analyzed the experimental data. P.-O.P. and P.G. wrote the manuscript.

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Correspondence to Peyman Golshani.

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Polack, PO., Friedman, J. & Golshani, P. Cellular mechanisms of brain state–dependent gain modulation in visual cortex. Nat Neurosci 16, 1331–1339 (2013). https://doi.org/10.1038/nn.3464

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