Research funding
BRAININITATIVE 1RF1-NS128895-01 8/17/2022 - 7/31/2025.
Functional connectivity of a brain-scale neural circuit for motion perception.
The goal is to investigate the brain-scale functional connectivity underlying the visually guided optomotor response in the genetically and optically accessible larval zebrafish.
1RF1-DA056376-01 | Collaboration with John Pearson 9/15/2022 - 9/14/2025
Real-time mapping and adaptive testing for neural population hypotheses.
The purpose of this project is to design new methods for testing hypotheses about how groups of neurons function together. Our goal is to build algorithms and software that will enable experiments to adapt in real time as new data arrive, refining hypotheses based on up to-the minute analysis. These tools will enable us to both explore complex data interactively and to perform more powerful experiments that give insights into how dynamical brain activity produces behavior
Completed funding
Sloan Research Fellowship 2021
We are glad our work is being recognized and selected to have a “unique potential to make substantial contributions to the field”.
Dissection of the neural microcircuitry of the zebrafish pretectum
Understanding the information processing that occurs in layers of interconnected neurons across multiple brain areas is a major challenge. For instance, the transformation of visual signals emerging from the retina into motor output requires many neurons distributed across the brain, and their role and connectivity remain elusive. Even the neural circuit underlying the zebrafish optomotor response (OMR), an innate visual orienting behavior, is surprisingly complex given the simple nature of the behavior and the organism, and it encompasses multiple brain regions and thousands of neurons with heterogeneous response properties. We are establishing an integrated experimental and computational platforms to precisely map neuronal-level circuit dynamics and their associated behavioral relevance within specific cell types to establish quantitative circuit models of this visuomotor transformation.
High-Resolution, Parallelized Imaging of Freely Swimming Zebrafish with a Gigapixel Microscope
The major goal of this project is to use optical microscopy, working with larval zebrafish (3-6 days post fertilization), to develop large scale optical assays that offer critical insights into the human body, our brain, and the diseases that affect us.
NIH BRAIN Initiative Planning Grant (R34) for Real-time, all-optical interrogation of neural micircuitry in the zebrafish
One of the major barriers to understanding how neural circuits give rise to behavior is that typical experimental preparations make it difficult to study these circuits across different brain areas. Recent advances in microscopy and calcium sensors have made it possible to simultaneously record up to thousands of individual neurons, and optical methods have made it possible to stimulate hundreds at a time, but current approaches, which stimulate only small subsets of predetermined neurons, are not adequate to the task of dissecting large-scale neural circuits. Here, we propose to develop new stimulation and computational methods that will allow us to test theories of the zebrafish optomotor response, a representative sensorimotor behavior. We will use these techniques to characterize the relationships among functionally defined groups of neurons as the data are collected. By using algorithms that adaptively choose holographic stimulation patterns of ~100 neurons in response to previously observed data, we will be able to increase data efficiency, simultaneously inferring multiple classes of functional connections between visually responsive neurons in the zebrafish pretectum. Once established, this approach will allow us to perform adaptive experiments that selectively perturb neural function based on data, speeding the process of model generation and hypothesis testing. Moreover, these tools will be applicable to other types of calcium imaging data, with broad implications for systems neuroscience.
DIBS Incubator Award for Gut-to-Brain Sensory Conduction in Zebrafish
Enteroendocrine cells (EECs) are specialized sensory cells within the intestinal epithelium that detect diverse compounds derived from diet and microbiota. EECs have long been known to respond to these enteric stimuli by releasing hormones that act upon the brain and other organs, but a recent discovery revealed that some EECs form synapses with afferent vagal neurons, mediating rapid communication with the brain. While EECs have been traditionally classified into multiple subtypes based on expression profile, it remains unknown which EEC subtypes communicate with the brain. Additionally, largely due to lack of a suitable model, it is unknown how EEC-mediated enteric stimuli affect brain-wide activity. Here, we propose to establish innovative technologies to define brain-wide activity in response to enteric stimuli mediated by specific EEC subtypes. This interdisciplinary collaboration with the Rawls Lab promises an integrative relational map linking specific enteric chemical stimuli, EEC subtypes, and the regions of the brain that respond to them, establishing the zebrafish as a model to study gut-brain communication.