Figure 3. Optogenetically inactivating Sst+ interneurons, compared to inactivating Pvalb+ interneurons, produces different linear transformations of FTCs.
(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.
Figure 3—figure supplement 1. Effects of inactivating Sst+ or Pvalb+ cells are mainly linear.
(a) Distribution of the R2 values from the linear regression analysis from units with activation of Sst+ cells (pink) and activation of Pvalb+ cells (light blue). High median R2 values demonstrate that in most units the effects of decreased inhibition are fit well by a linear framework (ChR2/Sst: median R2 = 0.81; ChR2/Pvalb: median R2 = 0.80).
Figure 3—figure supplement 2. Differences between inactivating Sst+ or Pvalb+ cells are present among broad-spiking, but not narrow-spiking, units.
(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.
Figure 3—figure supplement 3. Effects of inactivating Sst+ or Pvalb+ cells are not explained entirely by increases in spontaneous activity.
(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.
Figure 3—figure supplement 4. Differences between inactivating Sst+ or Pvalb+ cells are present even in unit populations whose firing rates are weakly affected by interneuron inactivation, as well as in strongly affected unit populations.
(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.
Figure 3—figure supplement 5. Inactivation of Sst+ cells, compared to inactivation of Pvalb+ cells, produces different proportions of linear effects, even after matching unit populations based on firing rate ratios.
(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 R2 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 R2 values demonstrate that most ratio-matched units are fit well by a linear framework (Arch/Sst: median R2 = 0.78; Arch/Pvalb: median R2 = 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.