Scott J Russo, PhD
img_Scott J Russo
PROFESSOR | Neuroscience
PROFESSOR | Psychiatry
Research Topics
Blood-Brain Barrier, Depression, Drug Design and Discovery, Immunology, Neurobiology, Neurophysiology, Neuroscience, Signal Transduction, Stress, Synapses, Synaptic Plasticity, Synaptogenesis
Multi-Disciplinary Training Area
Neuroscience [NEU]
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.

PhD, Graduate School and University Center of CUNY

University of Texas Southwestern Medical Center


Daniel H. Efron Basic Science Award from the

American College of Neuropsychopharmacology


Friedman Brain Institute Best Mentor Award

Friedman Brain Institute


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

Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device, biotechnology companies, and other outside entities to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their outside financial relationships.

Below are financial relationships with industry reported by Dr. Russo during 2023 and/or 2024. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Consulting or Other Professional Services Examples include, but are not limited to, committee participation, data safety monitoring board (DSMB) membership

  • PsychoGenics

Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website. Patients may wish to ask their physician about the activities they perform for companies.