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Somatostatin cells regulate sensory response fidelity via subtractive inhibition in olfactory cortex


Diverse types of local GABAergic interneurons shape the cortical representation of sensory information. Here we show how somatostatin-expressing interneurons (SOM cells) contribute to odor coding in mouse olfactory cortex. We find that odor-tuned SOM cells regulate principal cells through a purely subtractive operation that is independent of odor identity or intensity. This operation enhances the salience of odor-evoked activity without changing cortical odor tuning. SOM cells inhibit both principal cells and fast-spiking interneurons, indicating that subtractive inhibition reflects the interplay of multiple classes of interneurons.

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Figure 1: Optogenetic suppression of PCx SOM cells.
Figure 2: SOM cells provide subtractive inhibition in PCx.
Figure 3: Subtractive inhibition increases the discriminability of odor responses without altering odor tuning in PCx.
Figure 4: SOM cell suppression leads to the disinhibition of FS local interneurons.


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We thank M. Scanziani, K. Franks, P. Frady and members of the Isaacson and Scanziani laboratories for advice and discussions. Supported by the US National Institute on Deafness and Other Communication Disorders (R01DC04682, J.S.I.; 5F32DC013511, J.F.S.).

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Authors and Affiliations



J.F.S. and J.S.I. performed experiments, analyzed data and wrote the manuscript.

Corresponding author

Correspondence to Jeffry S Isaacson.

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The authors declare no competing financial interests.

Integrated supplementary information

Supplementary Figure 1 Expression of Arch-GFP in somatostatin-expressing interneurons.

Top, GFP fluorescence (green) in a coronal section of anterior piriform cortex from a SOM-cre mouse injected with AAV-2/9-CBA-Flexed-Arch-GFP. Middle, somatostatin immunofluorescence (red) from the same section. Bottom, merge of red and green channels. Left, low power images reveal robust expression of Arch-GFP and immunolabeled cell bodies limited to layer 3. Right, higher magnification image illustrating Arch-expressing somata immunopositive for somatostatin (overlap=79% ± 4%, n=104 cells from 3 mice).

Supplementary Figure 2 Properties of optogenetically tagged SOM cell units.

a) Histogram of LED modulation index (see Methods) for all single units. Red, putative SOM cell units (n=11); blue, non-SOM cell units (n=101). b) Odor intensity-response relationship of SOM cell units (n=7) shows consistent LED-induced suppression of SOM cell activity across different odor intensities. c) Odor tuning of SOM cell units (red, n=4) is similar to tuning of odor-activated principal cells (blue, n=18). d) Summary of firing activity for individual SOM cell units tested with different odors and odor intensities (grey lines, linear fits to individual units). Thick black line is average linear fit across all SOM cell units (n=11) shows a slope (m) of 0.2 (p<0.005) indicating a consistent LED-induced reduction in SOM cell activity.

Supplementary Figure 3 Effect of SOM cell suppression on layer 2/3 single-unit odor intensity–response relationship.

a) PSTHs from representative unit with and without LED illumination.b) Linear fit to the data shown in A reveals shift in y intercept (b) while slope (m) remains near unity. c) Summary of results from 21 units. Grey circles and grey lines; responses and linear fits to individual cells. Thick black line, average linear fit indicates additive shift in activity in response to SOM cell suppression.

Supplementary Figure 4 ChR2 activation of PV cells causes the divisive scaling of single-unit firing rates in piriform cortex.

a) Raster plots and trial histograms for a representative unit during application of different concentrations of amyl acetate under control (black) and PV cell activation (red) conditions. b) Linear fit indicating a significant reduction in slope of the relationship between LED off and LED on firing rates across odor intensity of the example unit in A. c) Summary of 4 experiments and 21 units (grey circles and grey lines) and average linear fit (thick black line) demonstrating that PV cell activation causes a linear offset and divisive scaling of firing rates in PCx (slope=0.46±0.08, p<0.0005, y-intercept=-0.34±0.24, p<0.001, n=21 units).

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Sturgill, J., Isaacson, J. Somatostatin cells regulate sensory response fidelity via subtractive inhibition in olfactory cortex. Nat Neurosci 18, 531–535 (2015).

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