A localized tracing technique to explore intra-amygdala functional and structural correlates of individual variability in behavioral response

IntroductionThe 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...

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Main Authors: Allie Lipshutz, Victoria Saltz, Kristin R. Anderson, Alessia Manganaro, Dani Dumitriu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Molecular Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnmol.2025.1347539/full
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author Allie Lipshutz
Allie Lipshutz
Victoria Saltz
Victoria Saltz
Victoria Saltz
Kristin R. Anderson
Kristin R. Anderson
Alessia Manganaro
Alessia Manganaro
Dani Dumitriu
Dani Dumitriu
Dani Dumitriu
author_facet Allie Lipshutz
Allie Lipshutz
Victoria Saltz
Victoria Saltz
Victoria Saltz
Kristin R. Anderson
Kristin R. Anderson
Alessia Manganaro
Alessia Manganaro
Dani Dumitriu
Dani Dumitriu
Dani Dumitriu
author_sort Allie Lipshutz
collection DOAJ
description IntroductionThe 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.MethodsIn 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 combine 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.Results and discussionWe 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.
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series Frontiers in Molecular Neuroscience
spelling doaj-art-52339099e62e440190d75427d05dcc402025-01-22T07:11:17ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992025-01-011810.3389/fnmol.2025.13475391347539A localized tracing technique to explore intra-amygdala functional and structural correlates of individual variability in behavioral responseAllie Lipshutz0Allie Lipshutz1Victoria Saltz2Victoria Saltz3Victoria Saltz4Kristin R. Anderson5Kristin R. Anderson6Alessia Manganaro7Alessia Manganaro8Dani Dumitriu9Dani Dumitriu10Dani Dumitriu11Division of Developmental Neuroscience, Department of Psychiatry, Columbia University, New York, NY, United StatesDivision for Child and Adolescent Health, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, United StatesDivision of Developmental Neuroscience, Department of Psychiatry, Columbia University, New York, NY, United StatesDivision for Child and Adolescent Health, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, United StatesZuckerman Institute, Columbia University, New York, NY, United StatesDivision of Developmental Neuroscience, Department of Psychiatry, Columbia University, New York, NY, United StatesDivision for Child and Adolescent Health, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, United StatesDivision of Developmental Neuroscience, Department of Psychiatry, Columbia University, New York, NY, United StatesDivision for Child and Adolescent Health, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, United StatesDivision of Developmental Neuroscience, Department of Psychiatry, Columbia University, New York, NY, United StatesDivision for Child and Adolescent Health, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, United StatesZuckerman Institute, Columbia University, New York, NY, United StatesIntroductionThe 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.MethodsIn 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 combine 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.Results and discussionWe 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.https://www.frontiersin.org/articles/10.3389/fnmol.2025.1347539/fullamygdala (amg)retrograde tracingcFosmicrocircuitsstress models of psychopathology
spellingShingle Allie Lipshutz
Allie Lipshutz
Victoria Saltz
Victoria Saltz
Victoria Saltz
Kristin R. Anderson
Kristin R. Anderson
Alessia Manganaro
Alessia Manganaro
Dani Dumitriu
Dani Dumitriu
Dani Dumitriu
A localized tracing technique to explore intra-amygdala functional and structural correlates of individual variability in behavioral response
Frontiers in Molecular Neuroscience
amygdala (amg)
retrograde tracing
cFos
microcircuits
stress models of psychopathology
title A localized tracing technique to explore intra-amygdala functional and structural correlates of individual variability in behavioral response
title_full A localized tracing technique to explore intra-amygdala functional and structural correlates of individual variability in behavioral response
title_fullStr A localized tracing technique to explore intra-amygdala functional and structural correlates of individual variability in behavioral response
title_full_unstemmed A localized tracing technique to explore intra-amygdala functional and structural correlates of individual variability in behavioral response
title_short A localized tracing technique to explore intra-amygdala functional and structural correlates of individual variability in behavioral response
title_sort localized tracing technique to explore intra amygdala functional and structural correlates of individual variability in behavioral response
topic amygdala (amg)
retrograde tracing
cFos
microcircuits
stress models of psychopathology
url https://www.frontiersin.org/articles/10.3389/fnmol.2025.1347539/full
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