Tools for Mapping and Engineering the Brain

The brain is a densely and precisely wired circuit made of heterogeneous cells, which themselves are complex computational devices made of an incredible repertoire of molecules.  Our group develops tools for mapping, recording from, controlling, and building brain circuits, in order to reveal how they work, as well as to open up new therapeutic avenues.  We have developed genetically-encoded reagents that, when expressed in specific neurons, enable their electrical activities to be precisely driven or silenced in response to millisecond timescale pulses of light.  I will give an overview of these optogenetic tools, adapted from natural photosensory and photosynthetic proteins, and discuss new tools we are developing, including molecules that enable multiplexed, noninvasive, and ultraprecise optical neural control, even of endogenous signaling pathways.  We are developing, often working in interdisciplinary collaborations, microfabricated hardware to enable complex and distributed neural circuits to be controlled and recorded in a fully 3-D fashion, new kinds of microscopes capable of whole-nervous system neural activity imaging, robots that can automatically record neurons intracellularly and integratively in live brain, and strategies for building 3-D brain circuits in vitro.  We aim to provide these tools to the neuroscience community in order to open up new fundamental as well as clinically relevant explorations of how to observe and repair brain circuits, and to apply these tools systematically to the mapping and engineering of entire brains.