Massive normalization of olfactory bulb output in mice with a 'monoclonal nose'

  1. Benjamin Roland
  2. Rebecca Jordan
  3. Dara L Sosulski
  4. Assunta Diodato
  5. Izumi Fukunaga
  6. Ian Wickersham
  7. Kevin M Franks
  8. Andreas T Schaefer
  9. Alexander Fleischmann  Is a corresponding author
  1. Collège de France, INSERM U1050, CNRS UMR 7241, France
  2. The Francis Crick Institute, United Kingdom
  3. University College London, United Kingdom
  4. Max-Planck-Institute for Medical Research, Germany
  5. Massachusetts Institute of Technology, United States
  6. Duke University, United States
  7. Faculty of Medicine, University of Heidelberg, Germany
8 figures

Figures

Figure 1 with 2 supplements
The ability of M71 transgenic mice to detect acetophenone is task-dependent.

(A, B) In a go/no go operant conditioning task, M71 transgenic mice fail to discriminate acetophenone from mineral oil (left panels). In contrast, M71 transgenic mice readily discriminate other …

https://doi.org/10.7554/eLife.16335.003
Figure 1—figure supplement 1
Schematic representation of the perturbation of the glomerular map of M71 transgenic mice with a 'monoclonal nose'.

(A) In wild-type mice, odors bind to subsets of odorant receptors (ORs), which results in the activation of subsets of olfactory sensory neurons (OSNs) and glomeruli in the olfactory bulb (OB). This …

https://doi.org/10.7554/eLife.16335.004
Figure 1—figure supplement 2
M71 transgenic mice fail to detect acetophenone in a go/no go operant conditioning task.

(A) Wild-type mice consistently discriminate acetophenone from its diluent mineral oil (black lines). Wild-type mice also discriminate between other pairs of odorants (ethyl acetate versus mineral …

https://doi.org/10.7554/eLife.16335.005
Normalization of odor-evoked mitral cell activity in M71 transgenic mice.

(A–I) Two-photon in vivo imaging of mitral cell odor responses in anesthetized mice. (A) Schematic of rabies-GCaMP3 injection into the lateral olfactory tract (LOT) and two-photon imaging of …

https://doi.org/10.7554/eLife.16335.006
Figure 3 with 1 supplement
Normalization of odor-evoked neural activity in M71 transgenic mice results in changes in response magnitudes and duration, and trial-to-trial variability.

(A–F) Two-photon in vivo imaging of mitral cell odor responses in anesthetized mice. (A, B) Odor tuning: the fraction of mitral cells responding to N odorants out of the 13 odorant test panel in …

https://doi.org/10.7554/eLife.16335.007
Figure 3—figure supplement 1
Response magnitudes and durations, and trial-to-trial variability of mitral cell odor responses in M71 transgenic mice.

(A–I) Two-photon in vivo imaging of mitral cell odor responses in anesthetized mice. (A) Cumulative frequency plots of the peak F/F values for ethyl acetate- and acetophenone-evoked mitral cell …

https://doi.org/10.7554/eLife.16335.008
Figure 4 with 1 supplement
Intrinsic and odor-evoked mitral cell activity in M71 transgenic mice.

(A–M) In vivo whole cell recordings in awake mice: comparison of physiological properties of mitral cells in control (black, n = 7) and M71 transgenic mice (red, n = 6). (A) Schematic of the …

https://doi.org/10.7554/eLife.16335.009
Figure 4—figure supplement 1
Patch clamp mitral cell recordings in anesthetized mice reveal increased acetophenone-evoked inhibition in M71 transgenic mice.

(A) Schematic: whole cell recordings in anesthetized mice. (B, C) Example traces showing single 1 s ethyl acetate presentations (shaded area) during mitral cell recordings from control (black) and …

https://doi.org/10.7554/eLife.16335.010
Figure 5 with 1 supplement
Increased acetophenone-evoked inhibition and theta coupling in M71 transgenic mice.

(A–H) In vivo whole cell recordings in awake mice. (A) Schematic of the experimental configuration. (B, C) Example trace of a 1% acetophenone presentation to a mitral cell in a control (B, black) …

https://doi.org/10.7554/eLife.16335.011
Figure 5—figure supplement 1
Individual acetophenone response traces.

In vivo whole cell recordings in awake mice. Mean spike-clipped traces in response to acetophenone at a concentration of 1% of absolute vapor pressure, averaged across all trials aligned to first …

https://doi.org/10.7554/eLife.16335.012
Figure 6 with 1 supplement
The olfactory bulb excitation/inhibition balance in M71 transgenic mice breaks down at high acetophenone concentrations.

(A–D) Two-photon in vivo imaging of mitral cell odor responses in anesthetized mice. (A, B) Representative maps of odor-evoked mitral cell activity elicited by acetophenone and ethyl acetate at …

https://doi.org/10.7554/eLife.16335.013
Figure 6—figure supplement 1
Response magnitudes and durations strongly increase with increasing acetophenone concentrations in M71 transgenic mice.

(A–H) Two-photon in vivo imaging of mitral cell odor responses in anesthetized mice. (A, B) Cumulative frequency plot of the peak DF/F values for mitral responses in control (A) and M71 transgenic (B

https://doi.org/10.7554/eLife.16335.014
Author response image 1
Increasing threshold stringency does not change the comparison of the fraction of responsive mitral cells or their response variability between M71 transgenic mice and controls.

(A) Mean fraction of neurons (horizontal line) responding to a given odorant at 0.01% vol./vol. dilution, with the response threshold set at 3.8 x SD, in control (black) and M71 transgenic (red) …

https://doi.org/10.7554/eLife.16335.015
Author response image 2
Clustering of mitral cell responses in controls and M71 transgenic mice.
https://doi.org/10.7554/eLife.16335.016

Download links