An inhibitory gate for state transition in cortex

  1. Stefano Zucca
  2. Giulia D’Urso
  3. Valentina Pasquale
  4. Dania Vecchia
  5. Giuseppe Pica
  6. Serena Bovetti
  7. Claudio Moretti
  8. Stefano Varani
  9. Manuel Molano-Mazón
  10. Michela Chiappalone
  11. Stefano Panzeri
  12. Tommaso Fellin  Is a corresponding author
  1. Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Italy
  2. Istituto Italiano di Tecnologia, Italy
  3. Center for Neuroscience and Cognitive Systems @UniTn, Istituto Italiano di Tecnologia, Italy
6 figures and 2 additional files

Figures

Figure 1 with 1 supplement
Firing activity of PV and SST interneurons during cortical up and down states in vivo.

(a) Fluorescence image showing a glass pipette (dotted white line) used for juxtasomal recordings from a PV positive interneuron (red cell) in a PVxTdTomato bigenic transgenic animal. (b) …

https://doi.org/10.7554/eLife.26177.002
Figure 1—source data 1

Source data for the analysis of the firing activity of PV and SST interneurons during up and down states.

https://doi.org/10.7554/eLife.26177.003
Figure 1—figure supplement 1
Up and down state detection from the LFP signal.

(a–c) Representative example of up/down state detection results. Up/down state periods (pink and purple shadows, respectively) as detected from membrane potential are shown in a, whereas states …

https://doi.org/10.7554/eLife.26177.004
Figure 1—figure supplement 1—source data 1

Source data for Up and Down state detection from the LFP signal.

https://doi.org/10.7554/eLife.26177.005
Figure 2 with 4 supplements
Temporal correlation between the activity of PV and SST interneurons and the LFP.

(a) Schematic representation of the experimental configuration for simultaneous LFP recording and fluorescence targeted juxtasomal recordings from PV interneurons. (b) Phase of firing distribution …

https://doi.org/10.7554/eLife.26177.006
Figure 2—source data 1

Source data for the analysis of the preferred phase of firing for PV and SST interneurons.

https://doi.org/10.7554/eLife.26177.007
Figure 2—source data 2

Source data for the analysis of the spike triggered phase speed velocity.

https://doi.org/10.7554/eLife.26177.008
Figure 2—figure supplement 1
Phase of firing strength and phase of firing reliability in PV interneurons.

(a) Histogram of the phase of firing strength (left) and histogram of the phase of firing reliability (right) for the representative PV interneuron showed in Figure 2b. Only spikes occurring during …

https://doi.org/10.7554/eLife.26177.009
Figure 2—figure supplement 2
Phase of firing strength and phase of firing reliability in SST interneurons.

(a) Histogram of the phase of firing strength (left) and histogram of the phase of firing reliability (right) for the representative SST interneuron showed in Figure 2h. Only spikes occurring during …

https://doi.org/10.7554/eLife.26177.010
Figure 2—figure supplement 3
Spike-triggered phase speed across the times of interneuron spikes close to state end.

(a) Phase speed of the recorded LFP (mean ± s.e.m.) triggered on a PV interneuron spike that was fired between 400 and 200 ms before the end of an up state, as a function of time. The spikes were …

https://doi.org/10.7554/eLife.26177.011
Figure 2—figure supplement 4
Correlation between LFP phase speed changes and firing properties of cortical interneurons.

(a) Plots of the LFP phase speed changes triggered by spikes close to the end of up states as a function of the circular variance of the phases of firing distributions in up states for PV (left) and …

https://doi.org/10.7554/eLife.26177.012
Figure 3 with 6 supplements
Optogenetic activation of PV and SST interneurons triggers up-to-down transitions.

(a) Top: schematic of the experimental configuration. ChR2 is expressed in PV cells (blue round circle) and intracellular recordings are performed from pyramidal neurons (grey triangle). Bottom: …

https://doi.org/10.7554/eLife.26177.013
Figure 3—source data 1

Source data for the analysis of membrane potential changes during photostimulation of PV or SST interneurons.

https://doi.org/10.7554/eLife.26177.014
Figure 3—figure supplement 1
Immunohistochemical analysis of ChR2 positive cells in PV- and SST-Cre animals.

(a–d) Confocal images of coronal cortical sections from a PV-Cre animal injected with AAV trasducing ChR2-mCherry. ChR2 positive cells (shown in a) largely stain for GABA (shown in b). ChR2-mCherry …

https://doi.org/10.7554/eLife.26177.015
Figure 3—figure supplement 1—source data 1

Source data for the immunohistochemical analysis of ChR2 positive cells in PV-Cre and SST-Cre injected mice.

https://doi.org/10.7554/eLife.26177.016
Figure 3—figure supplement 2
Functional analysis of PV and SST positive cells expressing ChR2.

(a–b) Confocal images of one coronal cortical section showing the expression of ChR2-mCherry in PV-Cre mice. Cells are shown at an expanded time scale in b. (c) Representative current-clamp …

https://doi.org/10.7554/eLife.26177.017
Figure 3—figure supplement 2—source data 1

Source data for the functional characterization of PV and SST interneurons expressing ChR2.

https://doi.org/10.7554/eLife.26177.018
Figure 3—figure supplement 3
Membrane potential speed in pyramidal neurons during optogenetically-evoked and spontaneous up-to-down state transitions.

(a) Schematic of the experimental configuration. (b) Representative intracellular recording showing an up-to-down state transition evoked by optogenetic activation (blue bar) of PV interneurons …

https://doi.org/10.7554/eLife.26177.019
Figure 3—figure supplement 3—source data 1

Source data for the analysis of membrane potential speed during optogenetically-evoked and spontaneous up-to-down state transitions.

https://doi.org/10.7554/eLife.26177.020
Figure 3—figure supplement 4
In vivo extracellular recordings of spontaneous cortical dynamics and photostimulation of PV positive interneurons expressing ChR2.

(a) Representative trace of an in vivo LFP recording (top) and corresponding spectrogram (bottom) showing the effect of optogenetic activation of PV interneurons during an ongoing up state. The …

https://doi.org/10.7554/eLife.26177.021
Figure 3—figure supplement 4—source data 1

Source data for the effect of PV photoactivation during up states on network activity.

https://doi.org/10.7554/eLife.26177.022
Figure 3—figure supplement 4—source data 2

Source data for the effect of PV photoactivation during down states on network activity.

https://doi.org/10.7554/eLife.26177.023
Figure 3—figure supplement 5
In vivo extracellular recordings of spontaneous cortical dynamics and photostimulation of SST positive interneurons expressing ChR2.

(a) Representative trace of an in vivo LFP recording (top) and corresponding spectrogram (bottom) showing the effect of optogenetic activation of SST interneurons expressing ChR2 during an ongoing …

https://doi.org/10.7554/eLife.26177.024
Figure 3—figure supplement 5—source data 1

Source data for the effect of SST photoactivation during up states on network activity.

https://doi.org/10.7554/eLife.26177.025
Figure 3—figure supplement 5—source data 2

Source data for the effect of SST photoactivation during down states on network activity.

https://doi.org/10.7554/eLife.26177.026
Figure 3—figure supplement 6
In vivo intracellular recordings of spontaneous cortical dynamics and photostimulation of PV or SST positive interneurons in non-anesthetized animals.

(a) Top: schematic of the experimental configuration. Bottom: morphological reconstruction of a recorded layer II/III pyramidal neuron. (b) Representative intracellular recordings showing the effect …

https://doi.org/10.7554/eLife.26177.027
Figure 4 with 4 supplements
Optogenetic inhibition of PV and SST cells prolongs the up state and triggers down-to-up transitions.

(a) Top: schematic of the experimental configuration. Bottom: morphological reconstruction of a representative recorded neuron. (b) Representative recordings from a pyramidal cell during optogenetic …

https://doi.org/10.7554/eLife.26177.028
Figure 4—source data 1

Source data for the analysis of membrane potential changes during photoinhibition of PV or SST interneurons.

https://doi.org/10.7554/eLife.26177.029
Figure 4—figure supplement 1
Functional analysis of PV and SST positive cells expressing Arch.

(a–b) Confocal images of coronal cortical sections showing the expression of Arch-eYFP in PV-Cre mice. (c) Representative current-clamp patch-clamp recordings in slices, showing the typical firing …

https://doi.org/10.7554/eLife.26177.030
Figure 4—figure supplement 1—source data 1

Source data for functional characterization of PV and SST interneurons expressing Arch.

https://doi.org/10.7554/eLife.26177.031
Figure 4—figure supplement 2
In vivo intracellular recordings of spontaneous cortical dynamics and photoinhibition of PV or SST positive interneurons in non-anesthetized animals.

(a) Top: schematic representation of the experimental configuration. Bottom: morphological reconstruction of a recorded layer II/III pyramidal neuron. (b) Representative intracellular recordings …

https://doi.org/10.7554/eLife.26177.032
Figure 4—figure supplement 3
In vivo extracellular recordings of spontaneous cortical dynamics and photoinhibition of PV positive interneurons expressing Arch.

(a) Representative trace of an in vivo LFP recording (top) and corresponding spectrogram (bottom) showing the effect of optogenetic stimulation (yellow line) of PV interneurons expressing Arch …

https://doi.org/10.7554/eLife.26177.033
Figure 4—figure supplement 3—source data 1

Source data for the effect of PV photoinhibition during up states on network activity.

https://doi.org/10.7554/eLife.26177.034
Figure 4—figure supplement 3—source data 2

Source data for the effect of PV photoinhibition during down states on network activity.

https://doi.org/10.7554/eLife.26177.035
Figure 4—figure supplement 4
In vivo extracellular recordings of spontaneous cortical dynamics and photoinhibition of SST positive interneurons expressing Arch.

(a) Representative trace of an in vivo LFP recording (top) and corresponding spectrogram (bottom) showing the effect of optogenetic stimulation (yellow line) of SST interneurons expressing Arch …

https://doi.org/10.7554/eLife.26177.036
Figure 4—figure supplement 4—source data 1

Source data for the effect of SST photoinhibition during up states on network activity.

https://doi.org/10.7554/eLife.26177.037
Figure 4—figure supplement 4—source data 2

Source data for the effect of SST photoinhibition during down states on network activity.

https://doi.org/10.7554/eLife.26177.038
Figure 5 with 1 supplement
Interneuron type-specific effect of optogenetic inhibitory manipulations.

(a) Schematic of the experimental configuration where PV cells were photoinhibited. (b) Firing rate of pyramidal neurons before (Pre), during (Light), and after (Post) PV photoinhibition during up …

https://doi.org/10.7554/eLife.26177.039
Figure 5—source data 1

Source data for the analysis of the interneuron type-specific effect of optogenetic inhibitory manipulations.

https://doi.org/10.7554/eLife.26177.040
Figure 5—figure supplement 1
Membrane potential speed in pyramidal neurons during optogenetically-evoked and spontaneous down-to-up state transitions.

(a) Schematic of the experimental configuration. (b) Representative intracellular recording showing a down-to-up state transition evoked by optogenetic inhibition (yellow bar) of PV interneurons …

https://doi.org/10.7554/eLife.26177.041
Figure 5—figure supplement 1—source data 1

Source data for the analysis of the membrane potential speed during optogenetically-evoked and spontaneous down-to-up state transitions.

https://doi.org/10.7554/eLife.26177.042
Figure 6 with 6 supplements
Local modulation of cortical interneurons causes large-scale state transitions.

(a) Schematic representation of the experimental configuration. Simultaneous dual patch-clamp recordings were performed in anesthetized mice during photoactivation of PV interneurons expressing …

https://doi.org/10.7554/eLife.26177.043
Figure 6—source data 1

Source data for the analysis of membrane potential changes in simultaneously recorded neurons during local optogenetic perturbation of PV and SST interneurons.

https://doi.org/10.7554/eLife.26177.044
Figure 6—figure supplement 1
Optogenetic activation of interneurons modulates network multi-unit activity over large cortical territories in anesthetized animals.

(a) Schematic representation of the experimental setup. Simultaneous extracellular recordings are performed in anesthetized mice during photoactivation of PV interneurons expressing ChR2. In this as …

https://doi.org/10.7554/eLife.26177.045
Figure 6—figure supplement 1—source data 1

Source data for the effect of local PV activation on network activity over large cortical territories.

https://doi.org/10.7554/eLife.26177.046
Figure 6—figure supplement 1—source data 2

Source data for the effect of local SST activation on network activity over large cortical territories.

https://doi.org/10.7554/eLife.26177.047
Figure 6—figure supplement 2
Large scale effect of PV and SST activation on multiunit activity using spatially-restricted DMD-based illumination.

(a) Optical setup for patterned illumination with a DMD (see Materials and methods for details). (b) Schematic configuration for simultaneous extracellular recordings during photoactivation of PV …

https://doi.org/10.7554/eLife.26177.048
Figure 6—figure supplement 2—source data 1

Source data for the large scale effect of PV activation on multiunit activity using spatially-restricted DMD-based illumination.

https://doi.org/10.7554/eLife.26177.049
Figure 6—figure supplement 2—source data 2

Source data for large scale effect of SST activation on multiunit activity using spatially-restricted DMD-based illumination.

https://doi.org/10.7554/eLife.26177.050
Figure 6—figure supplement 3
Temporal lag of optogenetically-induced state transitions across cortical areas.

(a) Top: schematic of the experimental configuration for dual patch-clamp recordings from two cortical neurons (Ch1 and Ch2) located 2 mm apart during local optogenetic manipulation of PV cells in …

https://doi.org/10.7554/eLife.26177.051
Figure 6—figure supplement 4
Local optogenetic modulation of interneurons modulates superficial pyramidal neurons over large cortical territories in non-anesthetized animals.

(a) Schematic representation of the experimental configuration for intracellular recordings of superficial pyramidal neurons in non-anesthetized animals during photoactivation of PV interneurons …

https://doi.org/10.7554/eLife.26177.052
Figure 6—figure supplement 4—source data 1

Source data for the analysis of membrane potential changes in pyramidal neurons located 2 mm far from modulated PV and SST cells in awake mice.

https://doi.org/10.7554/eLife.26177.053
Figure 6—figure supplement 5
Local optogenetic inhibition of interneurons modulates network MUA over large cortical territories in anesthetized animals.

(a) Schematic of the experimental setup. Simultaneous extracellular recordings are performed in anesthetized mice during photoinhibition of PV interneurons expressing Arch. (b) Top: example of a …

https://doi.org/10.7554/eLife.26177.054
Figure 6—figure supplement 5—source data 1

Source data for the effect of local PV inhibition on network activity over large cortical territories.

https://doi.org/10.7554/eLife.26177.055
Figure 6—figure supplement 5—source data 2

Source data for the effect of local SST inhibition on network activity over large cortical territories.

https://doi.org/10.7554/eLife.26177.056
Figure 6—figure supplement 6
Light transmission through the cortical tissue and density of opsin positive cells.

(a) Schematic representation of the illuminated brain volume using fiber optics. (b) Transmission fraction for yellow (λ = 594 nm) laser light as a function of the thickness of the cortical tissue. …

https://doi.org/10.7554/eLife.26177.057
Figure 6—figure supplement 6—source data 1

Source data for the evaluation of light transmission through cortical tissue and of the density of opsin-positive cells.

https://doi.org/10.7554/eLife.26177.058

Additional files

Source code 1

UP/DOWN state detection on LFP recordings and quantification of inhibitory interneurons firing properties.

Functions and scripts contained in this file have been used to produce data and plots reported in Figure 1 and Figure 1—figure supplement 1.

https://doi.org/10.7554/eLife.26177.059
Source code 2

Analysis of LFP and MUA recordings during optogenetic manipulation of interneurons.

Functions and scripts contained in this file have been used to produce data and plots reported in Figure 3—figure supplements 4 and 5 and Figure 4—figure supplements 3 and 4.

https://doi.org/10.7554/eLife.26177.060

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