Extreme or prolonged stress can profoundly alter both brain and body physiology, increasing susceptibility to conditions such as PTSD, panic disorder, and metabolic dysfunction. Stress acts through the autonomic nervous system, which includes:

• the sympathetic nervous system (SNS), responsible for “fight or flight” responses
• the parasympathetic nervous system (PNS), responsible for “rest and digest” processes

Chronic sympathetic activation can disrupt neuronal and astrocytic function, alter neuropeptide and neurotransmitter signaling, and impair cardiac, respiratory, metabolic, and immune systems.

The vagus nerve—often called the “wandering nerve”—is a central parasympathetic pathway connecting the brain to thoracic and abdominal organs. It regulates autonomic, cardiovascular, respiratory, gastrointestinal, immune, and endocrine functions. Vagus nerve stimulation, whether through implanted devices or mind–body practices such as yoga and breathwork, has shown therapeutic promise in modulating stress and restoring physiological stability.

The BrainBody Lab is committed to understanding how these brain–body pathways shape responses to traumatic stress. Our research addresses three central questions:

1. How does the brain–vagus–body axis influence fear and stress responses?
2. What mechanisms link traumatic stress to metabolic syndrome and energy imbalance?
3. How do astrocytes contribute to fear regulation, stress responses, and cardiorespiratory control?

To answer these questions, we employ a range of advanced techniques including optogenetics, chemogenetics, genetically modified mouse models, intersectional viral strategies, telemetry-based cardiorespiratory tracking, and validated behavioral paradigms for traumatic stress and fear.

Sanutha Shetty, Amir Farmanbar, Pamela Toh, Ramazan Yildiz, YoungUK Jang, Samuel Duesman, Aidan Warnock, Diego Espinoza, Sarah A. Stanley, Prashant Rajbhandari, Abha K. Rajbhandari. Disruption of Pre-Bötzinger Complex neuropeptidergic tonality controls fear and metabolic response. Under revision. https://www.biorxiv.org/content/10.64898/2026.01.01.697304v1

J. R. E. Carty, K. Devarakonda, R. M. O’Connor, A. Krek, D. Espinoza, M. Jimenez-Gonzalez, A. Alvarsson, R. F. Hampton, R. Li, Y. Qiu, S. Petri, A. Shtekler, A. Rajbhandari, Conner, M. Bayne, D. Garibay, J. Martin, V. Lehmann, L. Wang, K. Beaumont, I. Kurland, G. C. Yuan, P. J. Kenny & S. A. Stanley. Amygdala–liver signaling orchestrates glycaemic responses to stress. 2025. Nature.

Shetty S, Duesman SJ, Patel S, Huyhn P, Shroff S, Das A, Chowhan D, Sebra R, Beaumont K, McAlpine CS, Rajbhandari P, Rajbhandari AK. Sexually dimorphic role of diet and stress on behavior, energy metabolism, and the ventromedial hypothalamus. Biology of Sex Differences. doi: 10.1101/2023.11.17.567534. PubMed PMID: 39010139. *Corresponding author

Duesman SJ, Shetty S, Patel S, Ogale N, Mohamed F, Sparman N, Rajbhandari P, Rajbhandari AK. Sexually dimorphic role of the locus coeruleus PAC1 receptors in regulating acute stress-associated energy metabolism. Front Behav Neurosci. 2022;16:995573. doi: 10.3389/fnbeh.2022.995573. eCollection 2022. PubMed PMID: 36275856; PubMed Central PMCID: PMC9580361. *Corresponding author

Rajbhandari AK, Octeau CJ, Gonzalez S, Pennington ZT, Mohamed F, 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 Regulates Contextual Fear. J Neurosci. 2021 Apr 14;41(15):3446-3461. doi: 10.1523/JNEUROSCI.2564-20.2021. Epub 2021 Feb 26. PubMed PMID: 33637560; PubMed Central PMCID: PMC8051692. *Corresponding auth

Nagai J, Rajbhandari AK, Gangwani MR, Hachisuka A, Coppola G, Masmanidis SC, Fanselow MS, Khakh BS. Hyperactivity with Disrupted Attention by Activation of an Astrocyte Synaptogenic Cue. Cell. 2019 May 16;177(5):1280-1292.e20. doi: 10.1016/j.cell.2019.03.019. Epub 2019 Apr 25. PubMed PMID: 31031006; PubMed Central PMCID: PMC6526045.

Rajbhandari AK, Gonzalez ST, Fanselow MS. Stress-Enhanced Fear Learning, a Robust Rodent Model of Post-Traumatic Stress Disorder. J Vis Exp. 2018 Oct 13;(140). doi: 10.3791/58306. PubMed PMID: 30371665; PubMed Central PMCID: PMC6235522.