Circuit Diagrams

Abstract This project aims to develop the first Inverse Activity Marker (IAM) for detecting neuronal inhibition (broadly defined as the decrease of neuronal activities). The transcription of immediate early genes (IEGs) like c-Fos and Arc has been the most widely used for translating neuronal activity into stable, trackable histological labels to allow structural and functional interrogations. Existing activity targeting methods, either through direct detection of IEGs or engineered IEG promoters, are optimized for detecting the sustained increase of neural activity.

Project Summary Multiplexed imaging of brain cells and tissues can reveal critical details about the abundance and spatial organization of molecular targets. Sequential imaging methods based on iterative labeling and imaging enables practical higher multiplexing, but generally require complex fluidic setup with multiple rounds of slow buffer exchange. We propose to develop the thermal-plex method which removes complex and slow buffer exchange steps, and provides a fluidic-free, rapid sequential imaging method.

SUMMARY The brain is composed of thousands of highly specialized cell types that form very specific synaptic connections with each other. Together, these connections form neural circuits that are the structural basis of brain function. Despite their importance, synaptic connections amongst cell types are largely unascertained, because of the dearth of existing tools to do so.

ABSTRACT Understanding the function of neural circuits requires thorough investigation of two circuit elements: cell types and connectivity. The combination of axonal tracing with high-throughput DNA sequencing of genetically barcoded neurons has enabled the simultaneous characterization of anatomical and molecular identities of neurons and their projection fields. However, no high- throughput tools currently exist that allow us to map connections between presynaptic and postsynaptic neurons while identifying the cell types of mapped neurons.

Project Summary To determine the anatomical basis of complex neural behavior, it is critical to have the ability to trace more than one circuit simultaneously in the same animal. That’s because complex animal behaviors or neural computation should be understood through the interaction of more than one circuit – cooperative, antagonistic, or else. In addition, it is necessary to rapidly capture the connectivity information in the dynamically changing brains during development and learning.

Project Summary Aggression is an evolutionarily conserved behavior that controls social hierarchies and protects valuable resources like mates, food, and territory. In most cases, aggression is a necessary, adaptive component of social behavior. In humans, however, some forms of aggression are considered pathological when they threaten lives, increase the risk of psychiatric impairment in victims, and incur economic burdens on society. Considerable evidence indicates that aggression is associated with aberrant facial perception in humans.

Project Summary/Abstract Mental disorders that affect the hippocampus disrupt people’s ability to form one-shot memories. My goal is to lead an independent lab, linking biological properties of hippocampal neurons to the ability to perform memory- guided cognitive behaviors. To map cognitive behaviors to their underlying neural mechanisms, my lab will perform theoretical analyses and simulation of state-space models of cognitive behaviors, implementing these models in a recurrent network architecture with learning rules that match biological plasticity rules (Aims 3a, c).

PROJECT SUMMARY The vertebrate brain has evolved to enable complex social interactions, essential for survival. Brains of animals engaged in a shared social interaction exhibit inter-brain synchronization of neural activity, detectable at several levels of analysis. It remains unclear what aspects of social behavior are driven by these intriguing inter-brain dynamics.

Robust navigation, which is critical for an animal’s survival, requires the processing of complex sensory information spanning different modalities and time scales. Unlike human-engineered systems, where sensors are passive and modularized and decisions are typically made centrally, biological sensors constantly interact and influence each other, and behavioral decisions are made on different time scales with diverse goals. Further, such decisions are based on actively collected sensory information.

ABSTRACT Perceptually guided behavior involves a complex and dynamic interplay between external inputs and internal states that are related, for example, to alertness, motivation, expectations and attention. A wide range of evidence suggests that the representation, processing, and flow of sensory information in the primate brain is regulated by several neuromodulatory systems. However, our understanding of the physiological and behavioral impact of neuromodulatory signals during complex behaviors in primates is quite rudimentary and is lagging behind what is known in rodents.