University of Pécs, Hungary
University of Pécs, Hungary
Johann Helmut Brandstätter
Division of Animal Physiology, Department of Biology, FAU Erlangen-Nürnberg, Germany
"Signal transmission and adaptation at the first synapse in the visual system"
David Geffen School of Medicine, UCLA, USA
"Horizontal cell feedback and feed forward signaling mediated by calcium- and depolarization-dependent GABA vesicular release in the mammalian retina"
Weill Cornell Medicine, New York, USA
"Of Neurons and Pericytes: neurovascular approach to brain health and disease"
Save Sight Institute, University of Sidney, Australia
"Anatomical analysis of the rod pathway in human retina"
John Mora Eye Center, University of Utah, USA
"Multisensory integration in healthy and glaucomatous retinal ganglion cells"
MTA NAP Retinal Electrical Synapses Research Group, University of Pécs, Hungary
"Electrical Synapses of the Mammalian Retina Serve to Fine-tune the Ganglion Cell Output Signal"
The molecular architecture of the active zone of chemical synapses reflects the specific need of a given synapse. The photoreceptors of the retina transmit light signals over a wide, dynamic range of intensities, which requires continuous exocytosis of large numbers of synaptic vesicles at high rates. For this purpose, photoreceptors are equipped with a highly specialized chemical synapse, the ribbon synapse. In my presentation, I will discuss molecular constituents that facilitate the extraordinary performance of photoreceptor ribbon synapses.
Neurochemical / immunohistochemical findings showing the presence of both vesicular and synaptic proteins, and Ca channels in horizontal cell endings that support the idea that there is a GABA-mediated vesicular release from these cells. Functional assay showing the recycling of GABA vesicular transporter (VGAT) in horizontal cell terminals is calcium and depolarization dependent. Development of a horizontal cell VGAT-/- mouse line, and the demonstration that deletion of VGAT results in a lost of horizontal cell feedback to photoreceptors. Evidence that GABA acting in an autocrine fashion mediates in a pH dependent manner horizontal cell feedback to photoreceptors. Evidence for a novel pattern of GABA receptor subunit expression in the outer retina. Evidence that GABA antagonists and chemogenetic inhibition of horizontal cells inhibit horizontal cell feedback of photoreceptors.
Vision in darkness (scotopic vision) is mediated by rod photoreceptors by feeding their signals into rod bipolar cells (RBCs), which transfer the signal to AII amacrine cells. The AII amacrine cells are a crucial interneurone in the rod pathway because they contact both on-type bipolar cells (through gap junctions) and off-type bipolar cells (through glycinergic synapses). This connectivity makes AII amacrine cells a target for optogenetic induction of light sensitivity to restore vision in retinal diseases, but their distribution and sampling density in human retina is currently unknown. Here, we mapped AII cells and other rod pathway elements in post-mortem human donor eyes. Sections were double labeled for calretinin and glycine transporter to estimate the AII cell proportion. Other sections were processed for immunofluorescence to label rods, RBCs, and AII cells. We found AII cells have peak density at 1.5 mm with ~6,600 cells/mm2 and decline to ~1,500 cells/mm2 at eccentricities >6 mm. Rods peak at 3 mm with ~150,000 cells/mm2. Rod density gradually declines to ~80,000 cells/mm2 at 13 mm. RBCs have a peak density at 2.5 mm with ~15,000 cells/mm2. RBC density falls to ~6500 cells/mm2 at 10 mm. We conclude that there is convergence from rods to RBCs to AII cells throughout the retina. Our results indicate rod pathway spatial resolution would be limited by the peak density of AII cells peaking at 1.5 mm outside the fovea.
The function of the retina is mediated by elaborate neurovascular circuitry and could be dramatically altered by development, experience or during diseases. In this presentation, I will focus on some less appreciated aspects of common retinal dysfunctions. First, I will consider the role of maladaptive structural and functional changes in retinal circuitry following photoreceptor degeneration. This will be followed by examination of the retinal neurovascular unit, a circuit that incorporates neurons and vascular cells to control blood flow in the retina and how changes to this intricate interactions may contribute to variety of retinal diseases. In particular, in the model of diabetic retinopathy, we define a specific neurovascular circuit comprised of cholinergic amacrine cells and pericytes and demonstrate how this can be targeted and controlled with optogenetics. A better understanding of these mechanisms will not only extend our understanding of neurovascular interactions in the brain, but ultimately will provide new targets to treat vision loss in a variety of retinal diseases.
The presentation will address the molecular mechanisms of mechano- and thermotransduction in RGCs, including TRP channel activation. It will show how non-visual stimuli influence retinal output by regulating the intracellular concentrations of calcium and cAMP, gene expression and cytoskeletal remodeling.
Electrical synapses are abundant in the mammalian retina and they serve to summate, average, transmit or synchronize signals of interconnected retinal neurons. This presentation summarizes the sites of electrical synaptic interactions and the functions they play in shaping the spike code output of retinal ganglion cells. A particular emphasis will be given to inner retinal gap junctions formed by ganglion and/or amacrine cells that serve various forms of spike correlations. Finally, possible interactions of electrical and chemical synaptic signal transmission will also be outlined and their hypothetical functions will be proposed.