Scott J Russo, PhD
- PROFESSOR | Neuroscience
- PROFESSOR | Psychiatry
Research Topics:Behavioral Health, Bioinformatics, Biophysics, Computational Biology, Computer Simulation, Depression, Drug Design and Discovery, Integrins, Mathematical and Computational Biology, Membrane Proteins/Channels, Multiple Sclerosis, Protein Complexes, Protein Structure/Function, Signal Transduction, Stress, Synapses, Synaptic Plasticity, Synaptogenesis, Theoretical Biology, Theoretical Biophysics
Endowed Chair, Mount Sinai Professor in Affective Neuroscience
Dr. Russo is Professor of Neuroscience and Director of the Center for Affective Neuroscience at the Icahn School of Medicine at Mount Sinai. He obtained his Ph.D. in Psychology from the City University of New York in 2003. He then completed his postdoctoral work in Psychiatry and Psychology at the University of Texas Southwestern Medical Center before joining the faculty at the Icahn School of Medicine in 2008. Dr. Russo is known for his contributions to understanding the neural and immunological basis of neuropsychiatric disorders. His translational studies have identified novel disease mechanisms in depressed humans that play causal roles in the expression of depression-like behaviors in rodent models. He has also identified novel circuitry in the brain that control aberrant social behaviors leading to new perspectives about social dysfunction in neuropsychiatric illness. His work has been highly cited in the field and featured in the popular press. Thomson-Reuters listed him as a “highly cited researcher”. He has received numerous honors and awards in recognition of his work, including being named a Kavli National Academy of Science Frontiers Fellow in 2009, received the Johnson and Johnson/IMHRO Rising Star Translational Research Award in 2011 and elected fellow of the American College of Neuropsychopharmacology in 2016.
For more information about Dr. Russo, please visit the Russo Laboratory.
Multi-Disciplinary Training AreasNeuroscience [NEU], Pharmacology and Therapeutics Discovery [PTD]
PhD, Graduate School and University Center of CUNY
University of Texas Southwestern Medical Center
Daniel H. Efron Basic Science Award from the
Friedman Brain Institute Best Mentor Award
Icahn School of Medicine at Mount Sinai Faculty Council Award
Irma T. Hirschl/Monique Weill-Caulier Trust Research Award
Johnson & Johnson/IMHRO Rising Star Translational Research Award
Dr. Harold and Golden Lamport Research Award
Mount Sinai School of Medicine “Best Postdoctoral Mentor” Award
Neuroimmune mechanisms of depression
We have found that the pro-inflammatory cytokine interleukin-6 (IL-6) is highly up regulated in serum from stress susceptible mice as well as patients with treatment resistant major depression. The source of IL-6 is from bone marrow derived leukocytes, which is released in response to stress and can penetrate the brain and act directly on neural circuits controlling mood and emotion. In order to study peripheral IL-6, we’ve generated bone marrow chimeric mice that lacks the IL-6 gene only in bone marrow derived leukocytes and found the mice were behaviorally resilient to social stress. We also administered systemic monoclonal antibodies to sequester IL-6 and promote resilience. Janssen Pharmaceuticals partially funded our work testing such antibody sequestration strategies, and based on the results, they have recently launched a phase II clinical trial testing the efficacy of Sirukumab, a humanized monoclonal antibody against IL-6, in treatment resistant unipolar depression. Our current investigations aim to define the precise mechanisms by which peripheral immune cells and pro-inflammatory signals impact synaptic mechanisms in brain reward regions
Neural circuitry of aggression
A few years ago, we observed that highly aggressive mice found aggressive social interaction to be rewarding and we hypothesized that this may directly drive aggressive behavior. Using circuit tracing techniques and slice electrophysiology we identified key differences in the activation of brain reward circuitry between highly aggressive mice and their non-aggressive counterparts. Tools such as circuit specific optogenetics along with in vivo imaging of neural activity in awake behaving mice have allowed us to functionally probe neural circuits that control the rewarding aspects of aggressive behavior. Our initial results show strong activation of a GABAergic projection from the basal forebrain to the lateral habenula (lHb) that controls both aggression and its rewarding properties. Ongoing studies in my lab aim to further dissect the inputs to lHb impacting aggressive behavior and to identify the discreet neural codes associated with such aggressive behavior along with the molecular mechanisms driving these effects.
Synaptic mechanisms of addiction and depression
My lab has made fundamental contributions to understanding how brain reward systems adapt to chronic stress and cocaine. Utilizing advanced histological techniques, whole cell electrophysiology and 2 photon glutamate uncaging at single spines, we have found that chronic stress or cocaine increases excitatory synaptic transmission within the nucleus accumbens (NAc) in a cell- and synapse-type specific manner to control depression- and addiction-like behaviors. More recently, we have investigated the role of specific presynaptic glutamatergic inputs to the NAc in meditating depression-like behavior using circuit specific optogenetics and electrophysiology. We have found that social defeat stress, a mouse model of depression, increases synaptic transmission specifically at thalamo-striatal synapses on NAc medium spiny neurons and that this is both necessary and sufficient to promote a depression-like behavioral phenotype.