Theory & Data Analysis Tools

Project Summary/Abstract Volume electron microscopy is the only technique to-date that provides both sufficient resolution (100 μm) for the dense reconstruction of neuronal wiring diagrams. Currently, there exist two systems that have already delivered mm3-sized synaptic resolution electron microscopy stacks: Multi-beam scanning electron microscopy(Eberle et al. 2015; Ren and Kruit 2016) (mSEM) and Gridtape-based automated transmission electron microscopy(Yin et al. 2020; Maniates-Selvin et al. 2020) (Gridtape-TEM).

Project summary: This project will develop and validate a comprehensive toolset of novel technologies for imaging axonal projections across scales, and will deploy this toolset to map a complex system of cortico- subcortical projections in the macaque and human brain. We will combine the complementary strengths of three innovative microscopy techniques.

ABSTRACT Single-cell transcriptomics has revolutionized our understanding of neuronal diversity and enabled high-throughput characterization of molecular cell types across brain areas and species.

Project Summary/Abstract: Overall The overarching goal of this U19 program is to determine how neural computations across brain regions produce two core cognitive processes, working memory and decision-making, and thus to derive fundamental principles of brain function. This renewal application proposes to pursue powerful new themes that emerged from our previous work and to broaden our scope substantially.

Project Summary Oxytocin is a peptide hormone synthesized and released from the hypothalamus for reproduction, maternal care, and social behavior, as well as various ‘non-social’ aspects of internal state and physiological processes. Although sometimes referred to as a ‘trust’ hormone, a growing body of evidence across species and brain areas indicates that oxytocin can increase social salience, i.e., amplifying or enabling selective attention towards certain social stimuli, such as the sound of a crying infant or the presence of a threatening or high-status individual.

Direct local electrical stimulation (DLES) is an increasingly important therapeutic tool for treating brain disorders such as Parkinson’s, epilepsy, and OCD. There is considerable disagreement, however, as to how neural stimulation, especially at the scale of neurons, affects human brain function. This lack of understanding hampers the design and implementation of more effective stimulation approaches, particularly in the cortex.

Project Summary Public and private research funders have heavily invested in the application of implantable neurotechnologies to improve the management of treatment-resistant conditions and loss of function (e.g., deep brain stimulation (DBS) systems for recovery after traumatic brain injury (TBI), stroke, disorders of consciousness, movement disorders, and psychiatric disorders such as obsessive-compulsive disorder (OCD) and depression). These devices are trialed with people who have had severe impairments and treatment-resistant disorders for many years.

Project Summary/Abstract The BRAIN Initiative is supporting a broad portfolio of neuroscience research aimed at revolutionizing our understanding of the brain.

Project Summary/Abstract: The field of optogenetics — utilizing light to engage biological systems — is widely used for the dissection of neural circuits, cellular signaling and manipulating neurophysiological systems in awake, behaving animals. However, while many new opsins have been developed and are actively used, challenges still remain, and the current technology lacks a full toolbox for sub-cellular, spatiotemporal control of signaling — the predominant means for neuromodulator communication in the brain.

Project Summary Plasticity is a fundamental aspect of neuronal circuits across all species. It is at the base of learning and memory, sensory adaption, and many disease-related processes such as addiction, chronic pain or regeneration. On the molecular level biochemical mechanisms have been well described, but little is known on how these are coordinated in space and time within neuronal circuits of living brains.