The brain is made up of an incredible number of
different kinds of neuron, which vary in their shapes, molecular
compositions, and connectivity patterns, as well as in how they
change in different disease states. Understanding how these
different kinds of neuron work together in brain circuits to
implement perceptions, emotions, decisions, and actions, and
how flaws in specific neuron types result in brain disorders, is
an ongoing high priority for neuroscience. Over the last several
years we have developed a rapidly-expanding suite of
genetically-encoded reagents (e.g., ChR2, Halo, Arch, Mac, and
others) that, when expressed in specific neuron types in the
nervous system, enable their activities to be powerfully and
precisely activated and silenced in response to pulses of light.
These tools are in widespread use for analyzing the causal role
of defined cell types in normal and pathological brain
functions. We have begun to develop hardware to enable
complex and distributed neural circuits to be precisely
controlled, and for the network-wide impact of a neural control
event to be measured using distributed electrodes and fMRI.
We discuss our pre-clinical work on translation of such tools to
support novel ultraprecise neuromodulation therapies for
human patients.
