Brain, Vagus and Body Mechanisms of Fear and Stress
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.
1. How is the brain-vagus-body axis involved in modulating fear and stress?
This projects seeks to investigate the role of reciprocal connections between the brain and body (heart and lungs) via the vagus nerve in regulating traumatic fear, stress and cardiorespiratory functions.
2. What are the mechanisms that link traumatic stress and metabolic syndromes?
This project investigates the link between traumatic stress and metabolic changes with relevance to obesity, diabetes and other metabolic syndromes in stress.
3. How are brain astrocytes involved in regulating fear and stress?
This project is investigating the role of brain astrocytes and their modulation by neuropeptides in regulation of fear, stress and cardiorespiratory functions.
Funding & Awards
Current Funding support:
2020 Brain and Behavior Research Foundation NARSAD Young Investigator Grant
2020 Whitehall Foundation Grant
2020 Akira Arimura Young Investigator Grant for VIP/PACAP Research
2020 Friedman Brain Institute Scholars Award
2019 Arimura Award for Young Investigators for Excellence in VIP/PACAP Research
2018 Brain and Behavior Research Foundation NARSAD Young Investigator Award
2015 Ruth L. Kirschstein National Research Service Award (NRSA) Individual Postdoctoral Fellowship
2015 Trainee Professional Development Award, Society of Neuroscience
2015 Brain Research Institute Travel Award for Society of Neuroscience, UCLA
2012 Vilas Conference Grant for Society for Neuroscience Conference
2011 Competitive Travel Award (Neuroscience Training Program)
2010 Competitive Training Grant-T32 GM007507
2006 Social Science award, Olivet College
2004-2006: President’s List, Olivet College
2004-2006: Dean’s List, Olivet College
2004-2005: Heritage grant, Olivet College
2004-2005: S-Varney Scholarship, Olivet College
- Rajbhandari AK *, Octeau JC, Gonzalez S, Pennington ZT, Trott J, Chavez J, Ngyuen E, Keces N, Hong WZ, Neve RL, Waschek J, Khakh BS, Fanselow MS. A basomedial amygdala to intercalated cells microcircuit expressing PACAP and its receptor PAC1 in contextual fear regulation. 2021. Journal of Neuroscience. *-Corresponding author
- Rajbhandari P, Arneson D, Feng AC, Ahn IS, Diamante G, Zaghari N , Thomas BJ , Vergnes L , Lee SD , Rajbhandari AK, Reue K, Smale ST, Yang X and Tontonoz P. Single Cell Analysis Reveals Immune Cell-Adipocyte Crosstalk Regulating the Transcription of Thermogenic Adipocytes. 2019. Elife. (Note- first paper as a Principal Investigator with research contribution from the lab at ISSMS)
- Rajbhandari AK, Bakshi VP. Repeated norepinephrine receptor stimulation in the BNST induces sensorimotor gating deficits via corticotropin releasing factor. 2020. Neuropharmacology.
- Pennington ZT, Trott, JM, Rajbhandari AK, Li K, Walwyn WM, Evans CJ, Fanselow MS. Chronic opioid pretreatment potentiates the sensitization of fear learning by trauma. 2019. Neuropsychopharmacology.
- Nagai J, Rajbhandari AK, Gangwani MR, Hachisuka A, Coppola G, Sotiris MC, Fanselow MS, Khakh BS. Astrocytes induce acute hyperactivity in adult mice by reactivation of a latent synaptogenic cue. 2019. Cell.
- Rajbhandari AK, Gonzalez ST, Fanselow MS. Stress-Enhanced Fear Learning, a Robust Rodent Model of Post-Traumatic Stress Disorder. 2019. Journal of Visualized Experiments.
Abha Karki Rajbhandari
Master Graduate Student
Kennedy Blankenship, Research Volunteer.
Farzanna Mohamed, Research Associate. Current-Graduate Student at University of Michigan
Sydney Hart, Research Associate. Current-Graduate Student at NYU
Nazia Fyazi, Research Associate
Current available positions
We are looking for a postdoctoral candidate and a graduate student to join the lab. Pease email firstname.lastname@example.org