Research Career Programs

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).

The goal of this project is to provide the building blocks for an independent research program focused on the mechanisms by which neural networks incorporate multisensory cues into episodic memories. Discrimination of different contexts composed of distinct constellations of multisensory cues is a hallmark of both episodic memory and spatial navigation, two functions ascribed to the mammalian hippocampus.

Project Summary The ability to remember information, whether after short or long delays, is a fundamental human ability. There is enormous research into understanding working memory and long-term memory in isolation, but also a longstanding debate about the interactions between working memory and long-term memory.

PROJECT SUMMARY Efforts to understand the mechanisms of brain-based disease have been hindered by the limited ability of animal models to reflect the full complexity of human brain and behavior. Brain organoids represent a potential solution, allowing scientists to model human neurodevelopmental and disease processes in-vitro. These multicellular, three-dimensional tissue structures are derived from induced pluripotent stem cells and self-organize to recapitulate aspects of human cortical development.

Project Summary Towards the end of nervous system development, neural circuits are extremely plastic. Small perturbations during this time can cause lifelong circuit and behavioral changes. Not surprisingly, mounting evidence suggests that several neurodevelopmental disorders, including autism spectrum disorder and epilepsy, have origins in defective late neural circuit formation. During this late stage, neural circuits refinement takes place, and components of the mature behavior gradually appear. As this occurs, stimulus-independent bursts of activity sweep through neuronal populations.

PROJECT SUMMARY/ABSTRACT How the brain generates the correct number of neurons and how these neurons determine the size of their arbors to innervate the receptor field is a critical question in neurobiology. The Drosophila visual system is hard wired and iteratively organized into columns, providing an excellent model to answer these questions. Drosophila medulla multicolumnar neurons exhibit 5 to 750 neurons per cell type; each neuron class possesses a distinct morphology and projects its arbors across multiple columns in the optic lobe.

Project Summary There is currently an unmet need for accurate model systems of the human brain to study its cellular and molecular features. The cerebral cortex regulates our cognitive capacity, yet the cellular diversity, circuit formation, and function that establish this potential, largely remains a mystery. The cortex is expanded in humans compared to other species; it contains more cellular diversity and abundance, making model organisms limited for translational studies.

PROJECT SUMMARY A key problem in neuroscience is understanding how internal and external information are integrated in the brain to produce sensory experiences, cognition, and behavioral responses. This integration relies on flexible modulation of sensory processing in response to behavioral states like motivation, attention, and arousal. Neurons in the basal forebrain are key mediators of these behavioral states. At the same time, basal forebrain neurodegeneration in Alzheimer’s and Parkinson’s disease is associated with deficits in both cognitive and sensory processing.

Project Summary High-throughput profiling of hundreds of thousands of cells in the central nervous system (CNS) is currently underway.