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Synaptic mechanisms of adaptation and sensitization in the retina

Nature Neuroscience volume 16, pages 934–941 (2013)Cite this article

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Abstract

Sensory systems continually adjust the way stimuli are processed. What are the circuit mechanisms underlying this plasticity? We investigated how synapses in the retina of zebrafish adjust to changes in the temporal contrast of a visual stimulus by imaging activity in vivo. Following an increase in contrast, bipolar cell synapses with strong initial responses depressed, whereas synapses with weak initial responses facilitated. Depression and facilitation predominated in different strata of the inner retina, where bipolar cell output was anticorrelated with the activity of amacrine cell synapses providing inhibitory feedback. Pharmacological block of GABAergic feedback converted facilitating bipolar cell synapses into depressing ones. These results indicate that depression intrinsic to bipolar cell synapses causes adaptation of the ganglion cell response to contrast, whereas depression in amacrine cell synapses causes sensitization. Distinct microcircuits segregating to different layers of the retina can cause simultaneous increases or decreases in the gain of neural responses.

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Figure 1: Depressing and facilitating synaptic responses to temporal contrast.
Figure 2: Variations in contrast adaptation across bipolar cell synapses.
Figure 3: Frequency-dependent plasticity of synaptic transmission from bipolar cells.
Figure 4: Presynaptic calcium signals associated with depression and facilitation.
Figure 5: Stratification of amacrine cells synapses responding to contrast.
Figure 6: Pharmacological manipulation of the inhibitory input to bipolar cells removes facilitation.
Figure 7: Depressing and facilitating responses in neurons postsynaptic to bipolar cells.
Figure 8: Stratification of different groups of bipolar cell terminals in the inner retina.

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Acknowledgements

We thank all the members of the Lagnado laboratory for discussion. Support for this work was provided by the Medical Research Council and the Wellcome Trust (Programme grant 083220).

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Authors and Affiliations

  1. Medical Research Council Laboratory of Molecular Biology, Cambridge, UK

    Anton Nikolaev, Kin-Mei Leung, Benjamin Odermatt & Leon Lagnado

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  1. Anton Nikolaev
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  2. Kin-Mei Leung
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  4. Leon Lagnado
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Contributions

A.N., B.O. and L.L. designed the study. A.N., K.-M.L. and B.O. carried out the experiments. A.N., K.-M.L., B.O. and L.L. analyzed measurements. A.N., K.-M.L., B.O. and L.L. wrote the manuscript.

Corresponding author

Correspondence to Leon Lagnado.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–3 (PDF 7283 kb)

Supplementary Movie 1

In vivo imaging of synaptic transmission from bipolar cells responding to contrast. This movie is from the experiment analyzed in Figure 1A. The relative change in fluorescence dynamics (ΔF/F0) is shown on a pseudo-color scale for each ROI, where warmer colors represent stronger increases in sypHy fluorescence and colder colors represent falls. Real-time. Scale bar is 20 μm. (MOV 4071 kb)

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Nikolaev, A., Leung, KM., Odermatt, B. et al. Synaptic mechanisms of adaptation and sensitization in the retina. Nat Neurosci 16, 934–941 (2013). https://doi.org/10.1038/nn.3408

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