Synthetic Neurobiology
Revealing insights into the human condition and repairing brain disorders via novel tools for mapping and fixing brain computations.
Our brains and nervous systems mediate everything we perceive, feel, decide, and do—and act as our ultimate interface to the world. An outstanding challenge for humanity is to understand these neuromedia interfaces at a level of abstraction that enables us to engineer their functions: repairing pathology, augmenting cognition, and revealing insights into the human condition. The Synthetic Neurobiology group invents and applies tools to analyze and engineer brain circuits in both humans and model systems. Our current neuroengineering focus is on devising technologies for controlling the processing within specific neural circuit targets in the brain. We hope that this synthetic neurobiology approach to the brain will help us better understand—and engineer improvements upon—the nature of human existence.

Research Projects

  • Direct Engineering and Testing of Novel Therapeutic Platforms for Treatment of Brain Disorders

    Leah Acker, Bara Badwan, Changyang Linghu, Zixi Liu, Christian Wentz, Nir Grossman, Fumi Yoshida, Rin Yunis

    New 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 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

    Adam Marblestone, Alexander Clifton, Asmamaw Wassie, Guangyu Xu, Jae-Byum Chang, Kate Adamala, Ishan Gupta, Fei Chen, Daniel Martin-Alarcon, Manos Karagiannis, Nikita Pak, Paul Tillberg

    We 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

    Harbaljit Sohal, Anthony Zorzos
    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.
  • Molecular Reagents Enabling Control of Neurons and Biological Functions with Light

    Aimei Yang, Amy Chuong, Daniel Schmidt, Nathan Klapoetke
    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.
  • Recording and Data-Analysis Technologies for Observing and Analyzing Neural Circuit Dynamics

    Caroline Moore-Kochlacs, Deniz Aksel, Jake Bernstein, Jorg Scholvin, Jun Deguchi, Justin Kinney, Justine Cheng, Kiryl Piatkevich, Kris Payer, Mike Henninger, Moshe Ben-Ezra, Or Shemesh, Rebecca Luoh, Suhasa Kodandaramaiah, Young Gyu Yoon

    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

    Annabelle Singer, Brian Allen, Denis Bozic, Eunice Wu, Giovanni Talei Franzesi, Melina Tsitsiklis, Rita Ainane, Sean Batir, Sunanda Sharma

    We 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.