Parallele synaptische Mechanismen in der Netzhaut der Maus
Afrika-, Amerika- und Ozeanienbezogene Wissenschaften
Zusammenfassung der Projektergebnisse
The first synapse of the retina plays a fundamental role in the visual system. Because the rest of the visual system relies on it, it is critical that this synapse encodes information from the visual environment with the greatest accuracy and precision possible. Cone photoreceptor axon terminals contain multiple individual presynaptic sites, each relaying the light signal to one ON cone bipolar cell and several OFF cone bipolar cells, while two dendritic processes from a GABAergic interneuron, the horizontal cell, modulate the cone output via reciprocal feedback. The presence of these three partners within a single synapse has raised numerous questions, and the anatomical and functional complexity still is understood only partially. In particular, the mechanisms and functions of horizontal cell feedback to cone photoreceptors have remained unclear. In the project "Parallele synaptische Mechanismen in der Netzhaut der Maus" we aimed at understanding the multi-faceted role of the horizontal cell in the mouse retina. Controlling neurotransmitter release by modulating the presynaptic calcium level is a key mechanism to ensure reliable signal transmission from one neuron to the next. In this project, we showed that the glutamatergic transmission of cone photoreceptors in the mouse retina is shaped by different parallel reciprocal feedback mechanisms from postsynaptic horizontal cells. We provided evidence that ephaptic feedback sets the cone output gain by defining the basal calcium level, a mechanism that may be crucial for adapting cones to the background light level. In complement, proton-mediated feedback affected the size and shape of light-evoked presynaptic cone calcium signals in a strongly contrast-dependent way. We also provided functional evidence that GABA shapes light-evoked calcium signals in cones. Unexpectedly, GABA did not act as a direct feedback neurotransmitter, but rather acted through GABA autoreceptors on horizontal cells, thereby modulating ephaptic- and proton-mediated feedback pathways. Together, our results suggest that at the cone synapse direct ephaptic and proton-mediated feedback fulfil distinct functions to adjust the output of cones and that the efficacy of these feedback mechanisms is likely modulated by GABA release by horizontal cells in the outer retina. Thus, the complex feedback of horizontal cells contributes to a very controlled signal transfer at the very first synapse of the visual system. In addition to the identification of the complex feedback system at the mouse photoreceptor synapse, we aimed at understanding how the feedback is generated in the dendrites of the horizontal cells. The mouse retina contains a single type of horizontal cell that receives input from all cone photoreceptors within reach and modulates their output via the above described parallel feedback system. Furthermore, horizontal cells form an electrically coupled syncytium in the outer retina, the basis for a fast and efficient global signal processing underlying tasks such as large-scale, global contrast enhancement. However, it has been recently shown that horizontal cells can also act locally at the level of an individual cone photoreceptor axon terminal. To test whether the horizontal cell network is capable of such a local feedback, we used two-photon microscopy to record light stimulus-evoked calcium signals in horizontal cell dendrites. By selectively stimulating the two mouse cone types with green and UV light, we assessed whether signals from individual cones remain isolated within the horizontal cell dendritic tips or whether they spread across the dendritic arbour. The postsynaptic calcium signals measured in neighbouring horizontal cell dendritic tips varied markedly in their chromatic preference, arguing against global processing within the horizontal cell network. Rather, our experimental data and results from biophysically realistic modelling support the idea that horizontal cells can process cone input locally, extending the classical view of horizontal cell function.
Projektbezogene Publikationen (Auswahl)
- Differential regulation of cone calcium signals by different horizontal cell feedback mechanisms in the mouse retina. J Neurosci. 34(35):11826-43, 2014
Kemmler, Schultz, Dedek, Euler and Schubert
(Siehe online unter https://doi.org/10.1523/JNEUROSCI.0272-14.2014) - How do horizontal cells 'talk' to cone photoreceptors? Different levels of complexity at the cone-horizontal cell synapse. J Physiol. 595:5495-5506, 2017
Chapot, Euler and Schubert
(Siehe online unter https://doi.org/10.1113/JP274177) - Local Signals in Mouse Horizontal Cell Dendrites. Curr Biol. 27:3603-3615, 2017
Chapot, Behrens, Rogerson, Baden, Pop, Berens, Euler and Schubert
(Siehe online unter https://doi.org/10.1016/j.cub.2017.10.050) - The Functional Organization of Vertebrate Retinal Circuits for Vision. Oxford Research Encyclopedia of Neuroscience
Baden, Schubert, Berens and Euler
(Siehe online unter https://dx.doi.org/10.1093/acrefore/9780190264086.013.68)
