Optical Brain Dynamics Laboratory
Projects
Dissection of Maladaptive Social Behaviors at Cellular Resolution
Goal
Our laboratory pioneers state-of-the-art optical techniques to uncover how social information is encoded in the brain, in both health and disease states. Our goal is to elucidate the complex neural circuits underlying social behavior in health and disease.
Psychiatric disorders such as depression, anxiety, schizophrenia, autism spectrum disorders and bipolar disorder are often associated with challenges in social interaction. The neural circuits involved in social behavior are thought to be extremely complex, involving a wide variety of cell types. Historically, the study of these circuits has been limited, mostly to the study of one cell type at a time. The genetic tools we have developed allow multiplexing, i.e. we can simultaneously record and manipulate different cell populations at cellular resolution. Our group is using this comprehensive approach to better understand the circuit functions underlying social and other complex behaviors.
- Two-photon imaging and manipulation
- Fiber photometry
- Optogenetics
- Social behavior analysis
- Anatomical mapping
- Tissue clearing
Developing Genetically-Encoded Optical Tools to Link Brain Circuits with Behaviors
Goal
We are dedicated to developing new tools that enable us to explore minimally invasive modalities for understanding neural circuits in health and disease states, from the molecular level to whole-brain dynamics. Our goal is to identify mechanisms that may be potential targets for therapeutic intervention.
Unbiased real-time imaging across the whole brain would be a powerful approach to characterize behaviorally relevant neural activity. Existing methods (e.g., fMRI or 2p), while groundbreaking, are limited by temporal resolution, cell type specificity and imaging depth. To complement these technologies, we will develop novel genetically-encoded optical tools for minimally invasive modalities. Once developed, we will use these tools to measure brain-wide neural activity to identify socially relevant brain networks. Our goal is not just to observe, but to delve deep into the heart of neural interactions and behaviors.
- Protein engineering (structure-guided engineering, directed evolutionary engineering)
- High-throughput screening
- Photoacoustic
- Rational design of a high-affinity, fast, red calcium indicator R-CaMP2.
- Rational engineering of XCaMPs, a multicolor GECI suite for in vivo imaging of complex brain circuit dynamics
- Cortical Layer-specific Critical Dynamics Triggering Perception
- Genetically encoded calcium indicators to probe complex brain circuit dynamics in vivo
- A Flp-dependent G-CaMP9a transgenic mouse for neuronal imaging in vivo
- Structural basis for channel conduction in the pump-like channelrhodopsin ChRmine
- Structural basis for ion selectivity in potassium-selective channelrhodopsins.
Multimodal Optical Interrogation of Neural Circuits Regulating Social Interaction
Goal
Complex behaviors, such as social behavior, are not thought to be controlled by a single cell type or brain region but rather arise from the coordination of different cell types throughout the brain. Our goal is to regulate specific behaviors by integrating multimodal datasets that include brain-wide activity measurements, anatomical mapping and gene expression profiling. This research has the potential to pave the way for cellular/circuit-based disease classification and targeted interventions.
To understand the neural basis of social behavior and the etiology of disease states, it is critical to identify the relevant circuits and cell-types specific to each step, including sensory processing, integration of internal state information, decision-making and motor planning. Emerging technologies have allowed us to study the neural dynamics, genetic makeup and connectivity of individual circuits at great depth. However, a major challenge is the inability to integrate all three types of information from the same neurons, even though the brain is a collection of highly heterogeneous neurons. By leveraging the intersection of our laboratory’s strengths in protein engineering and optics, we address this problem and bridging these components from the single cell to the whole-brain scale through the development and application of state-of-the-art molecular optical tools. This research has the potential to pave the way for cellular/circuit-based disease classification and targeted interventions.
- Two-photon imaging and manipulation
- Optogenetics
- Anatomical mapping
- Single cell RNA sequence
- Tissue clearing
Our People
The lab, led by Masatoshi Inoue, PhD, features a diverse and interdisciplinary team with backgrounds in neuroscience, protein engineering and optics, dedicated to the multimodal interrogation of neural circuits regulating social behaviors.
