Understanding Circuits

Project Summary / Abstract Upcoming brain-wide descriptions of synaptic connectivity are poised to transform our understanding of brain circuitry in the same way single-cell genomics has revolutionized our understanding of cell type diversity. The challenge of relating whole-brain wiring diagrams to cell-type genetic properties must be overcome in order to fully realize the potential of these datasets.

PROJECT SUMMARY Sensory processing is a way to understand the nervous system in action. Behavioral context strongly affects sensory processing. For example, a brief visual stimulus is easier to detect if it appears in a predictable spatial location. This attention to visual space strongly enhances neural and behavioral responses to stimuli in those locations, but the detailed neural mechanisms spanning multiple brain areas remain unknown.

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.

PROJECT SUMMARY/ABSTRACT Individuals make choices and prioritize actions using complex processes that assign value to rewards and associated stimuli based on prior experience. In our modern environment, we are surrounded by an abundance of stimuli that fight for our attention and often hinder goal-directed behavior. Stimuli, or cues in our environment, attain control over behavior via Pavlovian learning, such that previously neutral stimuli that predict reward acquire motivational properties and are thereby transformed into attractive and desirable incentive stimuli.

Abstract Decades of research have revealed the principles of information processing that give rise to auditory spatial tuning and experience-dependent adaptive plasticity in the owl auditory system. This is a strong foundation on which to build a multiscale understanding of circuit function from synapse to behavior.

Many animals rely on their ability to navigate to the source of airborne odor plumes for survival. Studies dating back a century have shown that insects combine mechanosensory and olfactory cues to navigate, surging upwind when detecting odor but go crosswind or downwind when losing the signal. They also use bilateral information from their two antennae to turn toward higher odor concentrations. We recently discovered that in addition to wind direction and odor gradient, fruit flies detect the direction of motion of odors, independent of the wind.