Optogenetics for Analyzing and Engineering Neural Circuits

Optogenetics for Analyzing and Engineering Neural Circuits
Ed Boyden, PhD
Associate Professor, MIT Media Lab, McGovern Institute Departments of Biological Engineering and Brain and Cognitive Sciences
Case Western Reserve. Mar 29, 2012

Understanding how neural circuits work together to implement brain functions, and how these computations go awry in brain disorders, is a top priority for neuroscience.
Over the last several years we have discovered and developed a rapidly-expanding suite of genetically-encoded reagents (e.g., ChR2, Arch, Mac, ArchT, ChR65, 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.
In this talk I will give a brief overview of these tools, and discuss a number of new tools for neural activation and silencing that we are developing, including new molecules with augmented amplitudes, improved safety profiles, novel color and light-sensitivity capabilities, and unique new capabilities.
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 explore how these tools can be used to enable systematic analysis of neural circuit functions in the fields of emotion, sensation, and movement, and in neurological and psychiatric disorders.

Finally, we discuss our pre- clinical work on translation of such tools to support novel ultraprecise neuromodulation therapies for human patients.

3:20 high-dimensional space cell phenotype space technical mambo-jumbo

14:24 Three major optogenetic molecule classes
A. archaerhodopsins and bacteriorhodopsins (e.g. Arch, Mac, BR)
B. halorhodopsins (e.g. Halo/NpHR)
C. channelrhodopsins (e.g. ChR2) Boyden, E.S. (2011) Faculty of 1000 Biology Reports 3:11

18:44 Lentiviruses and adeno-associated viruses have intrinsic tropism for certain cell types (e.g., lenti-excitatory neurons of the cortex)