Neuroscience

Research focuses on understanding molecular and cellular processes that underlie behavior, with an emphasis on existing or novel targets for therapeutic intervention in psychiatric disorders. We have a specialized expertise in dopaminergic signaling and the function of midbrain dopamine neurons and their downstream targets. These circuits are thought to play an important role in the rewarding effects of abused drugs, as well as to figure importantly in the pathogenesis and treatment of schizophrenia. Work is carried out with purified proteins, in heterologous and primary cells in culture, in brain slice, as well as in behaving fruit flies and mice. We seek to understand how specific signaling processes and circuit activities are involved in the regulation of critical behaviors relevant to normal and abnormal behavior. An emerging focus is the identification of genes with high penetrance and large effect size associated with psychiatric disorders. These genes are studied in molecular and cellular model systems, including the generation of patient-derived induced pluripotent stem cells (IPSCs) and in genetically-engineered mice, with the goal of identifying molecular pathways that are dysregulated and might be targeted by novel therapeutics.

Research focuses on identifying brain circuits that are dysfunctional in psychiatric disorders as well as the targets of current and novel medications. Areas of specialized expertise include the serotonergic system, the response to stress, the hippocampus, adult neural stem cells as well as their contributions to mood and anxiety disorders. Work is carried out in animal models and utilizes a large battery of genetically engineered mice as well as a variety of stress procedures and behavioral readouts that encompass cognitive and mood-related functions. Most researchers are using a common set of technologies that include sophisticated behavioral paradigms in combination with state-of-the-art imaging techniques as well as optogenetic and chemogenetic strategies. This research focus is enabled by a set of core facilities that include two two-photon microscopes to perform calcium imaging in live mice, five mini-microscopes to perform calcium imaging in freely-behaving mice, two confocal microscopes to image whole fixed brains, and one two-photon microscope for iPS cell work. The resulting data is analyzed with machine-learning algorithms in collaboration with the Department of Computational Neuroscience of Columbia University. The ultimate goal is to understand how abnormal patterns of neural activity can produce pathological behavior and to utilize this knowledge to develop novel treatments for psychiatric disorders.

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We are the first department in a medical school to focus its basic research program on the development of brain and behavior as a basis for understanding the early origins of psychiatric illness. There are primary investigators who are interested in understanding how natural events and stressful experiences interact with genetic mechanisms to shape the course of normal and abnormal development. Ongoing studies use a variety of novel animal models to investigate the neurobiological substrates of attachment, separation anxiety, fear responses, aggression, emotion regulation, motivation, learning, and cognition. Studies involving human subjects examine the role of pre- and post-natal experiences on fetal, infant, child, and maternal behavior and physiology. Work in the division has revealed networks of neurobiological and behavioral processes within the fetal and early postnatal maternal environments which regulate the course of development and can shape adult outcomes and vulnerability to a number of clinical conditions. Research activities in the division are augmented by a close working relationship with the Institute for Developmental Sciences.

The Institute for Developmental Sciences is an organization within the Vagelos College of Physicians and Surgeons and the Department of Psychiatry that brings together 12 federally-funded scientists actively investigating developmental questions at all levels of inquiry. The faculty are highly collaborative and work together to produce translational, synergistic projects. To this mission, our faculty routinely brings between eight and ten million dollars of federal and other outside funding per year. The institute endowments support several activities including: 1) International Sackler Institute Scientific Summit, which brings together directors and junior scientists from each of seven Sackler Institutes; 2) seed funds to help support new directions in faculty research; 3) salary support for young investigators (Sackler Awardees); 4) travel awards to graduate students and postdoctoral fellows engaged in developmental research; 5) symposia; 6) the Sackler Winter Conference; 7) and funding for the annual Sackler Parent-Infant Grand Rounds speaker.

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The Denny Laboratory is interested in the molecular mechanisms underlying learning and memory.

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Our laboratory uses mouse genetic tools in an effort to understand the biology that underlies the symptoms of schizophrenia.

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The Neural Circuits Lab investigates the neural circuitry underlying psychiatric disorders by recording and manipulating neural activity in mouse models.

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The Veenstra-VanderWeele Lab is dedicated to helping children with autism spectrum disorder or obsessive-compulsive disorder.

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