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# Asymmetric effects of activating and inactivating cortical interneurons.

### Author information

- 1
- Neuroscience Graduate Program, University of California, San Francisco, San Francisco, United States.
- 2
- Center for Integrative Neuroscience, University of California San Francisco, San Francisco, United States.
- 3
- Coleman Memorial Laboratory, University of California, San Francisco, San Francisco, United States.
- 4
- Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, San Francisco, United States.

### Abstract

Bidirectional manipulations - activation and inactivation - are widely used to identify the functions supported by specific cortical interneuron types. Implicit in much of this work is the notion that tonic activation and inactivation will both produce valid, internally consistent insights into interneurons' computational roles. Here, using single-unit recordings in auditory cortex of awake mice, we show that this may not generally hold true. Optogenetically manipulating somatostatin-positive (Sst+) or parvalbumin-positive (Pvalb+) interneurons while recording tone-responses showed that Sst+ inactivation increased response gain, while Pvalb+ inactivation weakened tuning and decreased information transfer, implying that these neurons support delineable computational functions. But activating Sst+ and Pvalb+ interneurons revealed no such differences. We used a simple network model to understand this asymmetry, and showed how relatively small changes in key parameters, such as spontaneous activity or strength of the light manipulation, determined whether activation and inactivation would produce consistent or paradoxical conclusions regarding interneurons' computational functions.

#### KEYWORDS:

cortex; interneurons; mouse; neuroscience; optogenetics

- PMID:
- 27719761
- PMCID:
- PMC5123863
- DOI:
- 10.7554/eLife.18383

- [Indexed for MEDLINE]

**a**) Schematic of optogenetic manipulation in Arch/Sst mice in which green light directly hyperpolarizes Sst+ cells (green cells). (

**b**) Rasters of tone-evoked action potentials for a representative indirectly activated unit without (top) and with (bottom) inactivation of Sst+ cells. The black sine wave represents the duration of the sound, the green bar represents the duration and power of the light, and the yellow bar indicates the response period used to construct frequency tuning curves (FTCs). (

**c**) FTCs (mean ± SEMs) derived from tone-evoked firing rates (FRs) without (black) and with (pink) inactivation of Sst+ cells for the representative unit in (

**b**). Inset shows unit waveforms on trials without (black) and with (pink) inactivation of Sst+ cells. (

**d**) Distribution of the light-on to light-off tone-evoked FR ratios during the response period for frequency-tuned units. Green bars with pink outline indicate units with significantly suppressed FRs (n = 11 of 70 units), grayish pink bars indicate units with no significant change in FR (n = 15 of 70 units), and pink bars with black outline indicate units with significantly increased FRs (n = 44 of 70 units). (

**e–h**) As (

**a–b**), but in Arch/Pvalb mice, in which green light directly hyperpolarizes Pvalb+ cells (

**e**). (

**f**,

**g**) show the rasters and FTCs of a representative, indirectly-activated unit with and without inactivation of Pvalb+ cells. In (

**h**), green bars with light blue outline indicate units with significantly suppressed FRs (n = 5 of 59 units), grayish blue bars indicate units with no significant change in FR (n = 13 of 59 units), and light blue bars with black outline indicate units with significantly increased FRs (n = 41 of 59 units).

**DOI:**http://dx.doi.org/10.7554/eLife.18383.003

**a**) Immunostaining of a brain slice from an Arch/Sst mouse. (Left) Grayscale image of GFP stain. (Middle) Grayscale image of somatostatin stain. (Right) Merged image of GFP (green) and somatostatin (red) stains. Magenta arrows indicate three examples of putative Sst+ cells. Note that red and green somata mostly overlap. Scale bars are 50 microns. (

**b**) Immunostaining of a brain slice from an Arch/Pvalb mouse. (Left) Grayscale image of GFP stain. (Middle) Grayscale image of Pvalb stain. (Right) Merged image of GFP (green) and Pvalb (red) stains. Magenta arrows indicate three examples of putative Pvalb+ cells. Note that red and green somata mostly overlap. Scale bars are 50 microns.

**DOI:**http://dx.doi.org/10.7554/eLife.18383.004

**a**) An example unit’s mean firing rate (FR) ± SEMs relative to sound onset, without (black) and with (pink) inactivation of Sst+ interneurons. The black sine wave represents the duration of the sound, the green bar represents the duration and power of the light, the orange bar indicates the 50 ms time period used to calculate spontaneous FR, and the yellow bar indicates the 50 ms response period used to calculate tone-evoked FR. (

**b**) Same as (

**a**), for an example unit recorded from an Arch/Pvalb mouse without (black) and with (light blue) inactivation of Pvalb+ interneurons. (

**c**) The spontaneous FR with versus without light for each tuned unit whose sound-evoked FR was increased by light. Left: Arch/Sst, n = 44 units; right: Arch/Pvalb, n = 41 units. (

**d**) Spontaneous rate ratio (defined as light-on FR divided by light-off FR) for the units in (

**c**). Inactivation of Sst+ interneurons increases the spontaneous rate ratio (signrank p=7.6 × 10

^{−9}), as does inactivation of Pvalb+ interneurons (signrank p=2.4 × 10

^{−8}), but these ratios are not different from each other (ranksum p=0.054). (

**e**) Same as (

**c**), but for sound-evoked FRs (calculated as average spikes/second in the 50 ms after response onset). (

**f**) Sound-evoked rate ratio for the units in (

**e**). Inactivation of Sst+ interneurons increases the sound-evoked rate ratio (signrank p=7.5 × 10

^{−9}), as does inactivation of Pvalb+ interneurons (signrank p=2.2 × 10

^{−8}), but these ratios are not different from each other (ranksum p=0.26). (

**g**) Same as (

**c**), but for baseline-subtracted sound-evoked FRs (defined as evoked FR minus spontaneous FR). (

**h**) Baseline-subtracted sound-evoked ratio for the units in (

**g**). Inactivation of Sst+ interneurons increases the baseline-subtracted sound-evoked ratio (signrank p=8.0 × 10

^{−7}), as does inactivation of Pvalb+ interneurons (signrank p=5.2 × 10

^{−6}), but these ratios are not different from each other (ranksum p=0.77). (

**i**) Same as (

**c**), but for signal to noise ratio (SNR: defined as sound-evoked FR divided by spontaneous FR). (

**j**) SNR ratio for the units in (

**i**). Inactivation of Sst+ interneurons decreases SNR ratio (signrank p=2.6 × 10

^{−10}), as does inactivation of Pvalb+ interneurons (signrank p=1.9 × 10

^{−8}), but these ratios are not different from each other (ranksum p=0.081).

**DOI:**http://dx.doi.org/10.7554/eLife.18383.005

**a**) (Left) Schematic of a neuron’s FTC in the light-off (black) and light-on (green) conditions. (Right) Linear regression of light-off versus light-on firing rates (FRs) (measurements: black; fit: green; unity line: dashed gray). (

**b**) Multiplicative/divisive changes produce significant slopes (≠ 1). (

**c**) Additive/subtractive changes produce significant intercepts (≠ 0). (

**d**) Table showing all combinations of linear transformations of frequency tuning curves and their associated linear fits.

**DOI:**http://dx.doi.org/10.7554/eLife.18383.006

**a**) FTCs (mean ± SEMs) of representative units demonstrating all the combinations of linear transformations observed with inactivation of either Sst+ cells (pink) or Pvalb+ cells (light blue). (

**b**) Fraction of units that showed each kind of linear transformation with inactivation of Sst+ cells (pink) and inactivation of Pvalb+ cells (light blue). These proportions are significantly different between groups (Arch/Sst: n = 44 units from 12 mice; Arch/Pvalb: n = 41 units from 11 mice; Fisher’s exact test p=1.5 × 10

^{−3}). (

**c**) Population best-fit slope coefficients with inactivation of Sst+ cells (pink) and inactivation of Pvalb+ cells (light blue). Slopes were significantly different between groups (rank-sum p=0.01). Dark/light squares indicate units for which the slope was/was not significantly different from 1, respectively. Lines indicate population medians and lower/upper quartiles. (

**d**) Population best-fit y-intercepts, normalized by maximum firing rate, with inactivation of Sst+ cells (pink) and inactivation of Pvalb+ cells (light blue). Y-intercepts were significantly different between groups (rank-sum p=1.5 × 10

^{−4}). Dark/light squares indicate units for which the y-intercept was/was not significantly different from 0, respectively. Lines indicate population medians and lower/upper quartiles.

**DOI:**http://dx.doi.org/10.7554/eLife.18383.007

**a**) Distribution of the R

^{2}values from the linear regression analysis from units with activation of Sst+ cells (pink) and activation of Pvalb+ cells (light blue). High median R

^{2}values demonstrate that in most units the effects of decreased inhibition are fit well by a linear framework (ChR2/Sst: median R

^{2}= 0.81; ChR2/Pvalb: median R

^{2}= 0.80).

**DOI:**http://dx.doi.org/10.7554/eLife.18383.008

**a**) Best-fit slope coefficients for each unit as a function of action potential (AP) duration (trough-to-peak duration). Among the units with narrow-spiking waveforms (≤450 μs) whose activity was increased by light (Arch/Sst: n = 15; Arch/Pvalb: n = 15), Sst+ cell inactivation (pink) and Pvalb+ cell inactivation (light blue) produced slopes that were not significantly different (ranksum p=0.12). However, among the units with broad-spiking waveforms (>450 μs) whose activity was increased by light (Arch/Sst: n = 29; Arch/Pvalb: n = 26), Sst+ cell inactivation produced significantly larger slopes (rank-sum p=0.046) than Pvalb+ cell inactivation. Darker squares represent units for which the slope was significant. (

**b**) Normalized best-fit y-intercepts for each unit as a function of change in sound-evoked firing rate. Among the units with narrow-spiking waveforms (≤450 μs) whose activity was increased by light (Arch/Sst: n =15; Arch/Pvalb: n = 15), Sst+ cell inactivation (pink) and Pvalb+ cell inactivation (light blue) produced y-intercepts that were not significantly different (rank-sum p=0.23). However, among the units with broad-spiking waveforms (>450 μs) whose activity was increased by light (Arch/Sst: n = 29; Arch/Pvalb: n = 26), Pvalb+ cell inactivation produced larger y-intercepts (rank-sum p=0.00012) than Sst+ cell inactivation. Darker squares represent units for which the normalized y-intercept was significant.

**DOI:**http://dx.doi.org/10.7554/eLife.18383.009

**a**) An example unit’s FTC (mean ± SEMs) with (light blue) and without (black) inactivation of Pvalb+ cells. Inset shows the linear regression for light-off versus light-on firing rates (FRs) (measured FRs: black dots; fit: light blue line; confidence intervals: light blue shading; unity line: dashed gray line). (

**b**) Baseline-subtracted FTCs from the same unit in (

**a**). Note that the additive component (y-intercept) is still significant after baseline-subtraction, albeit smaller. (

**c**) Best-fit slope coefficients from baseline-subtracted units with inactivation of Sst+ cells (pink) and inactivation of Pvalb+ cells (light blue) were significantly different from each other (rank-sum p=0.0032). Dark/light squares indicate units for which the slope was/was not significantly different from 0, respectively. Lines indicate population medians and lower/upper quartiles. (

**d**) Normalized best-fit y-intercepts from baseline-subtracted units with inactivation of Sst+ cells (pink) and inactivation of Pvalb+ cells (light blue) were significantly different from each other (rank-sum, p=0.00052). Dark/light squares indicate units for which the y-intercept was/was not significantly different from 0, respectively. Lines indicate population medians and lower/upper quartiles.

**DOI:**http://dx.doi.org/10.7554/eLife.18383.010

**a**) Best-fit slope coefficients for each unit as a function of change in sound-evoked firing rate between the light-on and light-off conditions. Among the half of the units that were more weakly affected by interneuron inactivation (Arch/Sst: n = 25, pink; Arch/Pvalb: n = 18, light blue), Pvalb+ cell inactivation produced smaller slopes than Sst+ cell inactivation (rank-sum p=0.0087). Among the half of the units that were more strongly affected by interneuron inactivation (Arch/Sst: n = 19; Arch/Pvalb: n = 23), Pvalb+ cell inactivation produced smaller slopes than Sst+ cell inactivation (rank-sum p=0.025). Darker squares represent units for which the slope was significant. (

**b**) Normalized best-fit y-intercepts for each unit as a function of change in sound-evoked firing rate. Among the half of the units that were more weakly affected by interneuron inactivation (Arch/Sst: n = 25, pink; Arch/Pvalb: n = 18, light blue), Pvalb+ cell inactivation produced larger y-intercepts than Sst+ cell inactivation (rank-sum p=0. 029). Among the half of the units that were more strongly affected by interneuron inactivation (Arch/Sst: n = 19; Arch/Pvalb: n = 23), Pvalb+ cell inactivation produced larger y-intercepts than Sst+ cell inactivation (rank-sum p=0.005). Darker squares represent units for which the y-intercept was significant.

**DOI:**http://dx.doi.org/10.7554/eLife.18383.011

**a**) The linear regression analysis is limited to units from Arch/Sst mice and Arch/Pvalb mice that have similar sound-evoked firing rate ratios (Arch/Sst: n = 37 units from 12 mice; Arch/Pvalb: n = 37 units from 11 mice). (

**b**) Distribution of the R

^{2}values from the linear regression analysis from ratio-matched units with inactivation of Sst+ cells (pink) and inactivation of Pvalb+ cells (light blue). High median R

^{2}values demonstrate that most ratio-matched units are fit well by a linear framework (Arch/Sst: median R

^{2}= 0.78; Arch/Pvalb: median R

^{2}= 0.87) (

**c**) Fraction of units that showed each kind of linear transformation with inactivation of Sst+ cells (pink) or inactivation of Pvalb+ cells (light blue) were significantly different from each other (Arch/Sst: n = 37 units; Arch/Pvalb: n = 37 units; Fisher’s exact test p=0.0058). (

**d**) Best-fit slope coefficients from ratio-matched units with inactivation of Sst+ cells (pink) and inactivation of Pvalb+ cells (light blue) were significantly different from each other (rank-sum p=0.0064). Dark/light squares indicate units for which the slope was/was not significantly different from 0, respectively. Lines indicate population medians and lower/upper quartiles. (

**e**) Normalized best-fit y-intercepts from ratio-matched units with inactivation of Sst+ cells (pink) and inactivation of Pvalb+ cells (light blue) were significantly different from each other (rank-sum, p=0.0048). Dark/light squares indicate units for which the y-intercept was/was not significantly different from 0, respectively. Lines indicate population medians and lower/upper quartiles.

**DOI:**http://dx.doi.org/10.7554/eLife.18383.012

**a**) Schematic of optogenetic manipulation in ChR2/Sst mice in which blue light directly activates Sst+ cells (cyan cells). (

**b**) Rasters of tone-evoked action potentials for a representative suppressed unit without (top) and with (bottom) activation of Sst+ cells. The black sine wave represents the duration of the sound, the cyan bar represents the duration and power of the light, and the yellow bar indicates the response period used to construct FTCs. (

**c**) FTCs (mean ± SEMs) derived from tone-evoked firing rates (FRs) without (black) and with (red) activation of Sst+ cells for the representative unit in (

**b**). Inset shows unit waveforms on trials without (black) and with (red) activation of Sst+ cells. (

**d**) Distribution of the ratio of light-on to light-off FRs during the response period in ChR2/Sst mice for frequency tuned units. Red bars indicate units with significantly suppressed FRs (n = 64 of 97 units), grayish red bars indicate units with no significant change in FR (n = 19 of 97 units), and cyan bars with red outline indicate units with significantly increased FRs (n = 14 of 97 units). (

**e–h**) As (

**a–b**), but in ChR2/Pvalb mice, in which blue light directly activates Pvalb+ cells (

**e**). (

**f,g**) show the rasters and FTCs of a representative suppressed unit with and without activation of Pvalb+ cells. In (

**h**), blue bars indicate units with significantly suppressed FRs (n = 62 of 103 units), grayish blue bars indicate units with no significant change in FR (n = 20 of 103 units), and cyan bars with blue outline indicate units with significantly increased FRs (n = 19 of 103 units).

**DOI:**http://dx.doi.org/10.7554/eLife.18383.013

**a**) Immunostaining of a brain slice from a ChR2/Sst mouse. (Left) Grayscale image of GFP stain. (Middle) Grayscale image of somatostatin stain. (Right) Merged image of GFP (green) and somatostatin (red) stains. Magenta arrows indicate three examples of putative Sst+ cells. Note that red and green somata mostly overlap. Scale bars are 50 microns. (

**b**) Immunostaining of a brain slice from a ChR2/Pvalb mouse. (Left) Grayscale image of GFP stain. (Middle) Grayscale image of parvalbumin stain. (Right) Merged image of GFP (green) and parvalbumin (red) stains. Magenta arrows indicate three examples of putative Pvalb+ cells. Note that red and green somata mostly overlap. Scale bars are 50 microns.

**DOI:**http://dx.doi.org/10.7554/eLife.18383.014

**a**) An example unit’s mean firing rate (FR) ± SEMs relative to sound onset, without (black) and with (red) activation of Sst+ interneurons. The black sine wave represents the duration of the sound, the green bar represents the duration and power of the light, the orange bar indicates the 50 ms time period used to calculate spontaneous FR, and the yellow bar indicates the 50 ms response period used to calculate tone-evoked FR. (

**b**) Same as (

**a**), but of an example unit recorded from a ChR2/Pvalb mouse without (black) and with (blue) activation of Pvalb+ interneurons. (

**c**) The spontaneous firing rate (FR) (calculated as average spikes/second in the 50 ms before the stimulus) with versus without light for each tuned unit whose sound-evoked FR was increased by light. Left: ChR2/Sst, n = 64 units; right: ChR2/Pvalb, n = 62 units. (

**d**) Spontaneous rate ratio (defined as light-on FR divided by light-off FR) for the units in (

**a**). Activation of Sst+ interneurons decreases the spontaneous rate ratio (signrank p=1.1 × 10

^{−11}), as does activation of Pvalb+ interneurons (signrank p=5.1 × 10

^{−11}), but these ratios are not different from each other (ranksum p=0.56). (

**e**) Same as (

**c**), but for sound-evoked FRs (calculated as average spikes/second in the 50 ms after response onset). (

**f**) Sound-evoked rate ratio for the units in (

**e**). Activation of Sst+ interneurons decreases the sound-evoked rate ratio (signrank p=3.5 × 10

^{−12}), as does activation of Pvalb+ interneurons (signrank p=7.6 × 10

^{−12}), but these ratios are not different from each other (ranksum p=0.76). (

**g**) Same as (

**c**), but for baseline-subtracted sound-evoked FRs (defined as evoked FR minus spontaneous FR). (

**h**) Baseline-subtracted sound-evoked ratio for the units in (

**g**). Activation of Sst+ interneurons decreases the baseline-subtracted sound-evoked ratio (signrank p=2.2 × 10

^{−10}), as does activation of Pvalb+ interneurons (signrank p=7.6 × 10

^{−12}), but these ratios are not different from each other (ranksum p=0.31). (

**i**) Same as (

**c**), but for signal to noise ratio (SNR: defined as sound-evoked FR divided by spontaneous FR). (

**j**) SNR ratio for the units in (

**i**). Activation of Sst+ interneurons increases SNR ratio (signrank p=5.2 × 10

^{−12}), as does activation of Pvalb+ interneurons (signrank p=1.6 × 10

^{−11}), but these ratios are not different from each other (ranksum p=0.20).

**DOI:**http://dx.doi.org/10.7554/eLife.18383.015

**a**) FTCs (mean ± SEMs) of representative units demonstrating all the combinations of linear transformations observed with activation of either Sst+ cells (red) or Pvalb+ cells (blue). (

**b**) Fraction of units that showed each kind of linear transformation with activation of Sst+ cells (red) and activation of Pvalb+ cells (blue). Distribution of proportions is not significantly different between groups (ChR2/Sst: n = 59 units from 25 mice; ChR2/Pvalb: n = 57 units from 26 mice; Fisher’s exact test p=0.51). (

**c**) Best-fit slope coefficients for activation of Sst+ cells (red) and activation of Pvalb+ cells (blue). Slopes were not significantly different between groups (rank-sum p=0.68). Dark/light squares indicate units for which slope was/was not significantly different from 1, respectively. Lines indicate population medians and lower/upper quartiles. (

**d**) Best-fit y-intercepts, normalized by maximum firing rate, for activation of Sst+ cells (red) and activation of Pvalb+ cells (blue). Y-intercepts were not significantly different between groups (rank-sum, p=0.77). Dark/light squares indicate units for which y-intercept was/was not significantly different from 0, respectively. Lines indicate population medians and lower/upper quartiles.

**DOI:**http://dx.doi.org/10.7554/eLife.18383.016

**a**) Distribution of the R

^{2}values from the linear regression analysis from units with activation of Sst+ cells (red) and activation of Pvalb+ cells (blue). High median R

^{2}values demonstrate that response changes in most units are fit well by a linear framework (ChR2/Sst: median R

^{2}= 0.81; ChR2/Pvalb: median R

^{2}= 0.80).

**DOI:**http://dx.doi.org/10.7554/eLife.18383.017

**a**) Best-fit slope coefficients for each unit as a function of action potential (AP) duration (trough-to-peak duration). Among the units with narrow-spiking waveforms (≤450 μs) whose activity was suppressed by light (ChR2/Sst: n =29; ChR2/Pvalb: n = 12), Sst+ cell activation (red) and Pvalb+ cell activation (blue) produced similar slopes (ranksum p=0.85). Likewise, among the units with broad-spiking waveforms (>450 μs) whose activity was suppressed by light (ChR2/Sst: n = 30; ChR2/Pvalb: n = 45), Sst+ activation and Pvalb+ cell activation produced similar slopes (rank-sum p=0.51). Darker squares represent units for which the slope was significant. (

**b**) Normalized best-fit y-intercepts for each unit as a function of change in sound-evoked firing rate. Among the units with narrow-spiking waveforms (≤450 μs) whose activity was suppressed by light (ChR2/Sst: n = 29; ChR2/Pvalb: n = 12), Sst+ cell activation (red) and Pvalb+ cell activation (blue) produced similar y-intercepts (rank-sum p=0.22). Likewise, among the units with broad-spiking waveforms (>450 μs) whose activity was suppressed by light (ChR2/Sst: n = 30; ChR2/Pvalb: n = 45), Sst+ activation and Pvalb+ cell activation produced similar y-intercepts (rank-sum p=0.58). Darker squares represent units for which the normalized y-intercept was significant.

**DOI:**http://dx.doi.org/10.7554/eLife.18383.018

**a**) An example unit’s FTC (mean ± SEMs) with (blue) and without (black) activation of Pvalb+ cells. Inset shows the linear regression for light-off versus light-on firing rates (FRs) (measured FRs: black dots; fit: blue line; confidence intervals: blue shading; unity line: dashed gray line). (

**b**) Baseline-subtracted FTCs from the same unit in (

**a**). Note that the subtractive component (y-intercept) is no longer significant after baseline-subtraction. (

**c**) Best-fit slope coefficients from baseline-subtracted units with activation of Sst+ cells (red) and activation of Pvalb+ cells (blue) were similar to each other (rank-sum p=0.70). Dark/light squares indicate units for which slope was/was not significantly different from 0, respectively. Lines indicate population medians and lower/upper quartiles. (

**d**) Normalized best-fit y-intercepts from baseline-subtracted units with activation of Sst+ cells (red) and activation of Pvalb+ cells (blue) were similar to each other (rank-sum, p=0.19). Dark/light squares indicate units for which y-intercept was/was not significantly different from 0, respectively. Lines indicate population medians and lower/upper quartiles.

**DOI:**http://dx.doi.org/10.7554/eLife.18383.019

**a**) Slope coefficients for each unit as a function of change in sound-evoked firing rate between the light-on and light-off conditions. Among the half of the units that were more weakly affected by interneuron activation (ChR2/Sst: n = 28, red; ChR2/Pvalb: n = 30, blue), Pvalb+ cell activation produced similar slopes to Sst+ cell activation (rank-sum p=0.66). Among the half of the units that were more strongly affected by interneuron activation (ChR2/Sst: n = 31; ChR2/Pvalb: n = 27), Pvalb+ cell activation produced similar slopes to Sst+ cell activation (rank-sum p=0.43). Darker squares represent units for which the slope was significant. (

**b**) Normalized y-intercepts for each unit as a function of change in FR. Among the half of the units that were more weakly affected by interneuron activation (ChR2/Sst: n = 28, red; ChR2/Pvalb: n = 30, blue), Pvalb+ cell activation produced similar y-intercepts to Sst+ cell activation (rank-sum p=0.57). Among the half of the units that were more strongly affected by interneuron activation (ChR2/Sst: n = 31; ChR2/Pvalb: n = 27), Pvalb+ cell activation produced similar y-intercepts to Sst+ cell activation (rank-sum p=0.37). Darker squares represent units for which the y-intercept was significant.

**DOI:**http://dx.doi.org/10.7554/eLife.18383.020

**a**) Only units from both populations that have similar firing rate suppression ratios are kept for the analysis (ChR2/Sst: n = 52 units from 24 mice; ChR2/Pvalb: n = 52 units from 25 mice). (

**b**) Distribution of the R

^{2}values from the linear regression analysis from ratio-matched units with activation of Sst+ cells (red) and activation of Pvalb cells (blue). High median R

^{2}values demonstrate that most ratio-matched units are fit well by a linear framework (ChR2/Sst: median R

^{2}= 0.84; ChR2/Pvalb: median R

^{2}= 0.80). (

**c**) Fraction of units that showed each kind of linear transformation with activation of Sst+ cells (red) or activation of Pvalb+ cells (blue). These proportions are not significantly different between groups (ChR2/Sst: n = 52 units; ChR2/Pvalb: n = 52 units; Fisher’s exact test p=0.42). (

**d**) Best-fit slope coefficients from ratio-matched units with activation of Sst+ cells (red) and activation of Pvalb+ cells (blue). Slopes were not significantly different between groups (rank-sum p=0.58). Dark/light squares indicate units for which slope was/was not significantly different from 0, respectively. Lines indicate population medians and lower/upper quartiles. (

**e**) Normalized best-fit y-intercepts from ratio-matched units with activation of Sst+ cells (red) and activation of Pvalb+ cells (blue). Y-intercepts were not significantly different between groups (rank-sum, p=0.70). Dark/light squares indicate units for which y-intercept was/was not significantly different from 0, respectively. Lines indicate population medians and lower/upper quartiles.

**DOI:**http://dx.doi.org/10.7554/eLife.18383.021

**a**) Left: Waveforms (mean ± SD) from a putative Sst+ interneuron without (black) and with (red line, cyan outline) optogenetic activation. Middle: Peri-stimulus time histogram (mean ± SE) of the putative Sst+ interneuron without (black) and with (red line, cyan outline) optogenetic activation. Time zero indicates sound onset. Right: Frequency tuning curves (mean ± SE) without (black) and with (red line, cyan outline) optogenetic activation. Dotted lines indicate baseline firing rate without (black) and with (red) optogenetic activation. (

**b,c**) Same as (

**a**) for two other putative interneurons. In (

**c**), note that the putative Sst+ interneuron barely increases firing to the stimulus without optogenetic activation; but with optogenetic activation, its firing rate is often above 60 Hz. (

**d–f**) Same as (

**a–c**) for three putative Pvalb+ interneurons.

**DOI:**http://dx.doi.org/10.7554/eLife.18383.022

### Conflict of interest statement

The authors declare that no competing interests exist.

### Publication types, MeSH terms, Substances, Grant support

#### Publication types

#### MeSH terms

- Action Potentials
- Animals
- Auditory Cortex/physiology*
- Interneurons/chemistry
- Interneurons/physiology*
- Mice
- Models, Neurological
- Optogenetics
- Parvalbumins/analysis
- Somatostatin/analysis