Grant: Project Grant

The brain is made up of billions of neurons connected via thousands of connections, which together enable us to experience the world in its infinite beauty. To process information efficiently, however, neural circuits must connect in specific ways that ensure that there is little redundancy in the information they carry. Understanding the 'wiring diagram' of brain circuits and how they process information is a major challenge in contemporary neuroscience. This is especially important in the context of diseases, as many neurological deficits arise from the malfunction of specific neural circuits. The overarching goal of my research program is to develop advanced techniques to 'disentangle' specific circuits from the neural mesh and probe their functional and anatomical properties, in effort to understand how the brain computes information. To this end the direction-selective ganglion cell (DSGC) circuit in the retina is one of the best-characterized neural circuits in the CNS and serves as an excellent model system for understanding how the brain computes information. Recent serial EM studies have exhaustively identified the neural elements in the DS circuit of the mouse retina. The challenge now is to measure the functional properties of the circuit to understand the role of each element. While physiological analyses carried out over the last 50 years have revealed important features of the circuit's key components, the fundamental mechanisms underlying direction selectivity remain to be fully elucidated. In this proposal, we will combine conventional electrophysiological techniques with advances in high-speed imaging techniques to understand how the circuit is functionally wired and how this specific wiring can lead to the generation of robust direction selectivity over a variety of stimulus conditions.