Research

Extreme stress and/or fear can profoundly affect brain and body mechanisms leading to increased vulnerability for developing disorders such as post-traumatic stress (PTSD) and panic disorders. Stress exerts its effects on the brain and body via the sympathetic and parasympathetic systems which allow organisms to tackle a variety of stressors with “fight or flight” responses regulated by the sympathetic nervous system (SNS), and “rest and digest” responses, regulated by the parasympathetic nervous system (PNS).  Extreme or prolonged activation of the sympathetic systems can have detrimental effects at the level of neurons and astrocytes in various brain regions, neurotransmitter and neuropeptidergic systems, and organs like heart, lungs and gut in turn affecting central, metabolic, cardiorespiratory and immune functions. The vagus nerve, a major cranial nerve connecting the brain and body and known as the “wandering nerve”, is an important regulator of parasympathetic functions via innervations to the thoracic and abdominal organs, and the autonomic, cardiovascular, respiratory, gastrointestinal, immune, and endocrine systems. Direct vagus nerve stimulation using electrical devices or through mind/body practices such as yoga appear to be effective in diminishing stress, immune, and cardiorespiratory functions.

Karki lab is dedicated to understanding the reciprocal mechanisms between the brain and body axis via the sympathetic and parasympathetic modulators that affect or are affected by traumatic stress and associated changes in cardiorespiratory functions. Our research questions span along three main areas: 1) How is the brain-vagus-body axis involved in modulating fear and stress? 2) What are the mechanisms that link traumatic stress and metabolic syndromes?, and, 3) How are brain astrocytes involved in regulating fear, stress and cardiorespiratory functions? Our work is focused on the neuropeptidergic systems like PACAP (pituitary adenylate cyclase activating peptide) and CRF (corticotropin releasing factor) and the neurotransmitter norepinephrine. To answer our questions, we use cutting-edge tools and techniques such as optogenetics, chemogenetics, genetically modified mouse lines, intersectional viral approach, telemetry tracking of cardiorespiratory functions, behavioral models of traumatic stress and fear, and many others.