Nitric oxide modulates contrast suppression in a subset of mouse retinal ganglion cells

  1. Dominic Gonschorek
  2. Matías A Goldin
  3. Jonathan Oesterle
  4. Tom Schwerd-Kleine
  5. Ryan Arlinghaus
  6. Zhijian Zhao
  7. Timm Schubert
  8. Olivier Marre
  9. Thomas Euler  Is a corresponding author
  1. Werner Reichardt Centre for Integrative Neuroscience, University of Tübingen, Germany
  2. Institute for Ophthalmic Research, University of Tübingen, Germany
  3. GRK 2381 ’cGMP: From Bedside to Bench’, University of Tübingen, Germany
  4. Institut de la Vision, Sorbonne Université, INSERM, CNRS, France
  5. Hertie Institute for AI in Brain Health, Tübingen AI Center, University of Tübingen, Germany
  6. Bernstein Center for Computational Neuroscience, University of Tübingen, Germany
9 figures and 1 additional file

Figures

Overview of the experimental setup and recording procedure.

(a) Two-photon imaging of ganglion cell layer (GCL) somata in the whole-mounted ex vivo mouse retina. (b) Schematic ex vivo whole-mounted retina (dot marks optic disc; d, dorsal; t, temporal; v, …

Figure 2 with 1 supplement
Functional classification of mouse retinal ganglion cell (RGC) types.

(a) Illustration of the random forest classifier (RFC) to predict cell-type labels for Ctrl 1 of both datasets. For each cell, Ca2+ responses to chirp and moving bar, soma size, and p-value of …

Figure 2—figure supplement 1
Autocorrelation matrix of Baden et al., 2016, dataset.

(a) Autocorrelation matrix of average type responses per retinal ganglion cell (RGC) types of the Baden et al., 2016, dataset for responses to the chirp stimulus. Dashed boxes indicate functional …

Figure 3 with 2 supplements
Certain retinal ganglion cell (RGC) types are affected by adaptational and/or nitric oxide (NO)-induced effects, while others are unaffected.

(a) Left: Two representative mean Ca2+ responses of sequentially recorded RGC types showing no differences between Ctrl 1 (black) and Ctrl 2 (orange) (top: G1; bottom: G21). Right: Corresponding …

Figure 3—figure supplement 1
Adaptational, cell type-specific response changes without pharmacological perturbation.

(a) Mean Ca2+ responses of sequentially recorded retinal ganglion cell (RGC) types to the chirp (left) and moving bar (middle) to the Ctrl 1 (black) and Ctrl 2 (orange) conditions showing their …

Figure 3—figure supplement 2
Testing the effects of strychnine on different retinal ganglion cell (RGC) type responses.

(a) Mean Ca2+ responses of sequentially recorded RGC types to the chirp (left) and moving bar (middle) to the Ctrl (black) and Strychnine (blue) conditions showing their corresponding On-Off indices …

Disentangling nitric oxide (NO)-induced effects from adaptational response changes reveals type-specific NO modulation.

(a) Left: Difference between sequentially recorded Ctrl 2 and Ctrl 1 retinal ganglion cell (RGC) traces per type subdivided into eight features (ΔCtrl: ΔRCtrl2-Ctrl1). Color code indicates response …

Figure 5 with 1 supplement
Functional clustering of the G32 reveals three distinct types that are differently affected by nitric oxide (NO).

(a) Visual responses of G32 cells recorded from several experiments in response to the full-field chirp (left) and moving bar (right) stimuli. (b) Visual features extracted from chirp (top) and …

Figure 5—figure supplement 1
Further evaluation of the G32 functional clustering.

(a) Top: Mean response to the chirp (left) and moving bar (right) using n=2 clusters for the functional clustering. Bottom: Mean response to the chirp (left) and moving bar (right) using n=3 …

Spatial receptive fields (sRFs) are not affected by nitric oxide (NO) across various retinal ganglion cell (RGC) types.

(a) Representative estimated sRFs of six RGC types. Top: Estimated sRFs to Ctrl 1. Cross indicates RF center; solid line indicates outline of the Gaussian fit of the RF center; dashed outline …

Multi-electrode recordings and pseudo-calcium transformation.

(a) Representative retinal ganglion cell (RGC) type, G6 ‘(On-)Off ’JAM-B’ mix, recorded from one retina forming a mosaic. Three exemplary response traces of the same type. Cells are indicated in the …

Figure 8 with 3 supplements
Nitric oxide (NO) only affects temporal features of three distinct clusters of G32.

(a) Mean Ca2+-transformed responses to the chirp of the retinal ganglion cell (RGC) type G32. Top: Sequentially recorded RGC responses to the Ctrl (black) and DETA/NO (green) conditions. Bottom: …

Figure 8—figure supplement 1
Bayesian information criterion (BIC) as a function of number of clusters for G32 in the multi-electrode array (MEA)-dataset.

BIC as function of number of clusters for the G32 identified in the MEA-dataset. Arrow indicates the lowest BIC and the number of clusters to choose.

Figure 8—figure supplement 2
Pseudo-calcium and peristimulus time histograms of G32 clusters.

(a) Pseudo-calcium traces of clusters i–iii (left to right) in response to the chirp under Ctrl (black) and nitric oxide (NO) (green; top) as well as Ctrl and Wash-Out (orange; bottom) conditions. (b

Figure 8—figure supplement 3
Correlating G32 clusters of the Ca2+-dataset and multi-electrode array (MEA)-dataset.

(a) Correlation matrix showing the correlation coefficients between the pseudo-calcium G32 cluster responses to the chirp and the Ca2+-dataset G32 clusters. Color bar indicates Pearson correlation …

Author response image 1

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