Research Projects
Direct Engineering and Testing of Novel Therapeutic Platforms for Treatment of Brain Disorders
Leah Acker, Nir Grossman, Mike Henninger, and Fumi YoshidaNew technologies for controlling neural circuit dynamics, or entering information into the nervous system, may be capable of serving in therapeutic roles for improving the health of human patients–enabling the restoration of lost senses, the control of aberrant or pathological neural dynamics, and the augmentation of neural circuit computation, through prosthetic means. We are assessing the translational possibilities opened up by our technologies, exploring the safety and efficacy of optogenetic neuromodulation in multiple animal models, and also pursuing, both in our group and in collaborations with others, proofs-of-principle of new kinds of optical neural control prosthetics. By combining observation of brain activity with real-time analysis and responsive optical neurostimulation, new kinds of "brain co-processors" may be possible which can work efficaciously with the brain to augment its computational abilities, e.g., in the context of cognitive, emotional, sensory, or motor disability.
Exploratory Technologies for Understanding Neural Circuits
Brian Allen, Ishan Gupta, Rachel Bandler, Steve Bates, Fei Chen, Jonathan Gootenberg, Suhasa Kodandaramaiah, Daniel Martin-Alarcon, Paul Tillberg, Aimei YangWe are continually exploring new strategies for understanding neural circuits, often in collaboration with other scientific, engineering, and biology research groups. If you would like to collaborate on such a project, please contact us.
Hardware and Systems for Control of Neural Circuits with Light
The brain is a densely wired, heterogeneous circuit made out of thousands of different kinds of cells. Over the last several years, we have developed a set of fully genetically encoded "optogenetic" reagents that, when targeted to specific cells, enable their physiology to be controlled via light. To confront the 3D complexity of the living brain, enabling the analysis of the circuits that causally drive or support specific neural computations and behaviors, with our collaborators we have developed hardware for delivery of light into the brain, enabling control of complexly shaped neural circuits, as well as the ability to combinatorially activate and silence neural activity in distributed neural circuits. We anticipate that these tools will enable the systematic analysis of the brain circuits that mechanistically and causally contribute to specific behaviors and pathologies.Brian Allen, Jake Bernstein, Nir Grossman, Mike Henninger, Jorg Scholvin, Giovanni Talei Franzesi, Ash Turza, Christian Wentz, Anthony ZorzosMolecular Reagents Enabling Control of Neurons and Biological Functions with Light
Over the last several years our lab and our collaborators have pioneered a new area–the development of a number of fully genetically encoded reagents that, when targeted to specific cells, enable their physiology to be controlled via light. These reagents, known as optogenetic tools, enable temporally precise control of neural electrical activity, cellular signaling, and other high-speed natural as well as synthetic biology processes and pathways using light. Such tools are now in widespread use in neuroscience, for the study of the neuron types and activity patterns that mechanistically and causally contribute to processes ranging from cognition to emotion to movement, and to brain disorders. These tools are also being evaluated as components of prototype neural control devices for ultra-precise treatment of intractable brain disorders.Fei Chen, Yongku Cho, Amy Chuong, Nathan Klapoetke, Daniel Martin-Alarcon, Daniel Schmidt, Aimei YangRecording and Data-Analysis Technologies for Observing and Analyzing Neural Circuit Dynamics
Brian Allen, Jake Bernstein, Mike Henninger, Justin Kinney, Suhasa Kodandaramaiah, Caroline Moore-Kochlacs, Nikita Pak, Jorg Scholvin, Annabelle Singer, Al Strelzoff, Giovanni Talei Franzesi, Ash Turza, Christian Wentz, Ian Wickersham, Alex Wissner-Gross,The brain is a 3D, densely wired circuit that computes via large sets of widely distributed neurons interacting at fast timescales. In order to understand the brain, ideally it would be possible to observe the activity of many neurons with as great a degree of precision as possible, so as to understand the neural codes and dynamics that are produced by the circuits of the brain. And, ideally, it would be possible to understand how those neural codes and dynamics emerge from the molecular, genetic, and structural properties of the cells making up the circuit. Along with our collaborators, we are developing a number of innovations to enable such analyses of neural circuit dynamics. These tools will hopefully enable pictures of how neurons work together to implement brain computations, and how these computations go awry in brain disorder states.
Understanding Neural Circuit Computations and Finding New TherapeuticTargets
Leah Acker, Brian Allen, Steve Bates, Sean Batir, Jake Bernstein, Gary Brenner, Tim Buschman, Suhasa Kodandaramaiah, Carolina Lopez-Trevino, Patrick Monahan, Caroline Moore-Kochlacs, Sunanda Sharma, Annabelle Singer, Giovanni Talei Franzesi, Fumi YoshidaWe are using our tools–such as optogenetic neural control and brain circuit dynamics measurement–both within our lab and in collaborations with others, to analyze how specific sets of circuit elements within neural circuits give rise to behaviors and functions such as cognition, emotion, movement, and sensation. We are also determining which neural circuit elements can initiate or sustain pathological brain states. Principles of controlling brain circuits may yield fundamental insights into how best to go about treating brain disorders. Finally, we are screening for neural circuit targets that, when altered, present potential therapeutic benefits, and which may serve as potential drug targets or electrical stimulation targets. In this way we hope to explore systematic, causal, temporally precise analyses of how neural circuits function, yielding both fundamental scientific insights and important clinically relevant principles.
