Signal processing in horizontal cells of the mammalian retina – coding of visual information by calcium and sodium action potentials
Final Report Abstract
The results obtained in this project represent an important contribution to a better understanding of the function of horizontal cells as modulatory interneurons in the outer retina. We were able to detect the expression of the synaptically relevant ionotropic glutamate receptors GluA2, GluA3, and GluA4, the voltage-gated calcium channel subtypes Cav2.2 and Cav3.2, and the voltage-gated sodium channel subtypes Nav1.2, Nav1.3, and Nav1.6 using bioinformatical analysis and immunocytochemical staining in mouse retinal horizontal cells, and we could localize these channels at the subcellular level. The pharmacological findings suggest an involvement of Cav2.2 in the generation of action potentials, whereas T-type calcium channels, as well as voltage-dependent sodium channels apparently do not play an essential role in the initiation of spikes. Furthermore, in a theoretical work comparing artificial neuronal networks with a microand a macroconnectome, we investigated the importance of the structure of neural networks for their functionality in general. In addition, we designed and tested several self-learning algorithms to automatically analyze the rather complex synaptic activity of horizontal cells in an acute slice preparation and in primary cortical cultures. In comparison with existing manual and semi-automatic approaches, our methods prove to enable an objective, error-insensitive, and time-saving analysis of synaptic signals based on pattern recognition by artificial neural networks. Due to a very unfavorable corona and disease-related situation, some experiments could not be performed as planned and some of the data have not been published yet. The surprisingly small calcium signals and the problems with cell type-specific expression of the calcium sensor GCaMP6f have significantly hampered the proposed spatial analysis of signal propagation using imaging techniques, especially along the so-called axon of horizontal cells. In summary, given the inventory and localization of ion channels important for signalling, we have fulfilled a key requirement for modeling signal generation and propagation in horizontal cells. Together with the electrophysiological and pharmacological data obtained in this project, a detailed description of the function of horizontal cells based on biophysical and structural principles appears within reach.
Publications
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Analysis of tetrodotoxin-sensitive sodium and low voltage-activated calcium channels in developing mouse retinal horizontal cells. Experimental Eye Research, 195, 108028.
Feigenspan, Andreas; Ohs, Alexandra; von Wittgenstein, Julia; Brandstätter, Johann Helmut & Babai, Norbert
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Ionotropic glutamate receptors in the retina – a bioinformatical meta-analysis. Cold Spring Harbor Laboratory.
Pircher, Bianca; Pircher, Thomas & Feigenspan, Andreas
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The structure dilemma in biological and artificial neural networks. Scientific Reports, 11(1).
Pircher, Thomas; Pircher, Bianca; Schlücker, Eberhard & Feigenspan, Andreas
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A novel machine learning-based approach for the detection and analysis of spontaneous synaptic currents. PLOS ONE, 17(9), e0273501.
Pircher, Thomas; Pircher, Bianca & Feigenspan, Andreas
