Dynamics of a retinal synapse, as studied by simultaneous measurement of presynaptic capacitance and postsynaptic current

A major challenge in neuroscience is to understand how the physiological and biophysical properties of cells and synapses in a sensory system give rise to functional circuits that transform the neuronal representations of sensory stimuli. The key question is to determine how specific molecular mechanisms have been adapted to the signal processing taking place in specific synaptic circuits in the central nervous system. The goal of the current project is to investigate the dynamic properties of a synapse b etween two specific neurons in the retinal network that is essential for night vision. In an in vitro retinal slice preparation, we will perform dual recordings from pairs of presynaptic rod bipolar cells and postsynaptic rod (AII) amacrine cells and simu ltaneously measure the presynaptic membrane capacitance (in order to stydy exocytosis) and the postsynaptic current (in order to study evoked responses). The presynaptic recordings will be targeted directly to the axon terminal compartment of the rod bipo lar cells. An important aspect of the project is to establish a realistic morphological model of rod bipolar cells recorded in this way and to use theoretical simulations to validate capacitance measurements from terminals of intact cells (Hallermann et a l., 2003). Important scientific goals of the project will be to determine rates in the synaptic vesicle cycle in rod bipolar terminals (including size of the releasable pool, existence of functionally distinct pools with differential release kinetics, max imal rate of exocytosis, time course of endocytosis), to determine the quantitative relation between the presynaptic calcium current and the increase in capacitance, to determine the quantitative relation between the presynaptic increase in capacitance an d the postsynaptic excitatory current, and to investigate important mechanisms of short-term modulation of transmitter release.