Monosynaptic tracing using rabies virus has become a standard component of the systems neuroscience toolkit, allowing identification and manipulation of neurons directly presynaptic to any targeted neuronal population in the brain. However, while this retrograde monosynaptic tracing system is now well established, an anterograde counterpart, which would allow identification and manipulation of neurons directly postsynaptic to a target cell group, has never been constructed. Here we propose to meet this important outstanding need, with a multipronged and tiered strategy designed to ensure the delivery of at least one anterograde monosynaptic tracing system to the field, and possibly of several such systems, of differing levels of ease of use, power, and sophistication. Success of any of our aims will provide neuroscience with a transformative new tool for understanding and manipulating neural circuits throughout the brain, in many species including rodents and primates. Achievement of all of our aims will provide a versatile and powerful array of techniques to systems neuroscientists, allowing a broad set of new experimental designs that are likely to quickly yield major insights into the organization of neuronal circuits and the biological bases of normal cognition and behavior and the dysfunctions underlying neurological and mental disorders.
We will construct several novel systems for identification and manipulation of neurons directly presynaptic to any targeted neuronal population in the brain. Achievement of our aims will provide a versatile and powerful array of techniques to systems neuroscientists, allowing a broad set of new experimental designs that are likely to quickly yield major insights into the organization of neuronal circuits and the biological bases of normal cognition and behavior and the dysfunctions underlying neurological and mental disorders.
