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ORIGINAL RESEARCH article

Front. Mol. Neurosci.
Sec. Neuroplasticity and Development
Volume 18 - 2025 | doi: 10.3389/fnmol.2025.1347539
This article is part of the Research Topic Neurodevelopmental Origins of Resilience Across Species and Life Course View all 6 articles

A Localized Tracing Technique to Explore Intra-Amygdala Functional and Structural Correlates of Individual Variability in Behavioral Response

Provisionally accepted
Allie Lipshutz Allie Lipshutz 1,2Victoria Saltz Victoria Saltz 1,2,3Kristin Anderson Kristin Anderson 1,2Alessia Manganaro Alessia Manganaro 1,2Dani Dumitriu Dani Dumitriu 1,2,3*
  • 1 Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York, United States
  • 2 Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York City, New York, United States
  • 3 Zuckerman Mind Brain Behavior Institute, The Fu Foundation School of Engineering and Applied Science, Columbia University, New York, New York, United States

The final, formatted version of the article will be published soon.

    The neurobiological basis for individual variability in behavioral responses to stimuli remains poorly understood. Probing the neural substrates that underlie individual variability in stress responses may open the door for preventive approaches that use biological markers to identify at-risk populations. New developments of viral neuronal tracing tools have led to a recent increase in studies on long range circuits and their functional role in stress responses and social behavior. While these studies are necessary to untangle largescale connectivity, most social behaviors are mediated and fine-tuned by local subregional circuitry. In order to probe this local, interregional connectivity, we present a new combination of a neuronal tracing system with immediate early gene immunohistochemistry for examining structural and functional connectivity within the same animal. Specifically, we combined a retrograde transsynaptic rabies tracing system with cFos colocalization immediately after an acute stressor to elucidate local structural and stress-activated connectivity within the amygdala complex in female and male mice. We show how specific structural and functional connections can predict individual variability along a spectrum of social approach/avoidance following acute social defeat stress. We demonstrate how our robust method can be used to elucidate structural and functional differences in local connectivity that mediate individual variability in behavioral response.

    Keywords: amygdala (amg), retrograde tracing, cfos, microcircuits, Stress models of psychopathology

    Received: 01 Dec 2023; Accepted: 08 Jan 2025.

    Copyright: © 2025 Lipshutz, Saltz, Anderson, Manganaro and Dumitriu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Dani Dumitriu, Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, 10032, New York, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.