Research Projects

Project Summary/Abstract The objective of “Brain Computer Interfaces and Disability: Developing an Inclusive Ethical Framework (BCI- DEF)” is to use structured vignettes, video-supported interviews, and a deliberative democracy approach to assess and analyze diverse, critical stakeholder perspectives about the benefits, risks, and ethical challenges of Brain Computer Interface (BCI) technology. BCIs measure and interpret brain signals and interface with a device to allow users to perform a task, such as communication or movement.

Project Summary Neurotechnologies used to treat brain disorders and diseases can drastically change brain function and behavior, monitor brain activity, and collect and transmit personal health data. Industry-academia (IA) partnerships play a critical role in bringing neurotechnologies to market for public benefit. However, there are significant ethical issues that emerge from these partnerships, especially given the unique capacities of neurotechnologies.

ABSTRACT Morphology is an essential phenotype in the characterization of cells and their states. It reflects the progression of functional cellular processes, such as morphogenesis, migration, or dendrite arborization, and can be indicative of disease. Delineating the molecular pathways that underlie morphological phenotypes is critical to understanding the relation between genetic pathways, morphology, and function of cells in the brain.

The brain is a massively interconnected network of specialized circuits. Understanding how these circuits support sensation, perception, cognition, and action requires measuring activity patterns within and across regions, but the measurements themselves do not produce insight into the structure or function of the underlying neuronal system. Insight requires the applications of quantitative methods that relate neuronal activity patterns to experimentally measurable variables, including things like present and past sensory inputs, current location, and current or future motor outputs.

Project Summary/Abstract The overarching objective of this proposal is to develop a robust approach to map the brain's connections quickly, accurately, and cost-effectively. Past efforts to address the challenge of teasing apart the complex connectome of the mammalian brain were subject to a steep trade-off between throughput/efficiency and resolution. Two cutting-edge neuronal mapping techniques—barcoding based connection mapping (BARseq) and expansion microscopy (ExM)—have proven they can achieve efficient and high-resolution connection mapping within mammalian neural tissue.

Abstract Neural circuits composed of interconnected neurons with distinct properties lay the physical foundation of any brain function. Identifying connections between individual neurons is central to understand how information is processed and propagated in the brain. While emerging high throughput light microscopy technologies are highly promising in allowing whole brain scale imaging at the single cell level, optical resolution limitation prevents their use in differentiating densely labeled neuronal processes in the same brain.

The complex behaviors of all vertebrates are determined by the brain where neurons are connected by synapses. The average volume of synapses corresponds to a sphere of ~400 nm radius—a size scale that can barely be resolved using conventional optical microscopy methods. Synapses are tightly packed with molecular assemblies of synaptic vesicles, synaptic and cytoskeletal proteins and neurotransmitter receptors.

At the end of 2020, the IARPA MICrONS program will conclude with an automated reconstruction of all neurons in a cubic millimeter of mouse visual cortex, along with the neurons’ synaptic connectivity and calcium-imaged responses to video stimuli. We believe that this dataset could become the most widely used resource in the field of cortical circuits, but more work is required to realize this potential.

Abstract The goal of this proposal is to develop robust in vitro human cell-derived microphysical systems which faithfully represent key features of the developing human neocortex in vivo. Our work addresses three key challenges that have limited the development of these systems to date: (1) Building robust and reproducible organoids at high throughput. To obtain meaningful, statistically significant results from genetic and non-genetic perturbations, it is necessary to develop organoid systems which are robust and can be reproducibly assayed in large numbers.

PROJECT SUMMARY Understanding of many aspects of the human brain is currently limited due to the lack of appropriate model systems that recapitulate the heterogenous nature of the human brain and the ethical and practical limitations of working with human brain tissue from patients. To overcome these challenges, we employ three-dimensional brain organoids, derived from human pluripotent stem cells, that recapitulate key features of human cortical development.