Dynamics of synaptic transmission in the rod pathway of the retina

A considerable challenge in neuroscientific research is to explain processes at the systems level in terms of mechanisms at cellular and molecular levels. The retina serves as an ideal model system amenable to experimental approaches that directly aim to bridge this gap. With respect to the sensory processing taking place in the retina, a fundamental challenge is to understand how specific molecular and cellular mechanisms are adapted to the signal processing taking place in identified synaptic circuits. The principal objective of the current project is to understand, at a molecular and microphysiological level, the integrative dynamics of a neuronal network that plays a pivotal role for vision under dark-adapted conditions. To achieve this goal, we will use a combination of experimental (multielectrode patch-clamp, dynamic clamp, capacitance measurements, ultrafast drug application, morphological single-cell reconstruction) and theoretical (computer simulations of ion channels, single cells and small net works) investigations of bipolar cells and amacrine cells in the rod pathway of the retina. A very important technical aspect of the project is to aggressively extend our ability to perform electrophysiological recordings from ever smaller neuronal proces ses by combining infrared videomicroscopy with fluorescence imaging. First, we aim to increase our understanding the synaptic transmission between rod bipolar cells and AII and how diabetic hyperglycemia might change the functional properties of the invol ved AMPA receptors. Second, we aim to increase our understanding of the functional properties and consequences of electrical coupling between AII amacrine cells. Finally, we aim to increase our understanding of the role of voltage-gated ion currents and G ABAergic feedback in shaping the response properties of rod bipolar cells. A successfull project will increase our understanding of the dynamics of a synaptic microcircuit of fundamental importance for human vision.