Projection Neurons from Infralimbic (IL) to the Basolateral Amygdala (BLA) are Critical for the Expression of Social Familiarity induced Anxiolysis (SoFiA) in rats
Abstract
Mental health is crucially linked to social behavior. Healthy social behavior involves learning to adapt emotional responses to social cues, for example learning to suppress anxiety through social familiarity, or social familiarity-induced anxiolysis (SoFiA). SoFiA is well documented and forms the basis for interpersonal therapy, however, the neural mechanisms of SoFiA are unclear. SoFiA is modeled in rats by employing the social interaction habituation (SI-hab) protocol.
Using SI-hab protocol, it has been determined that SoFiA represents social safety learning, which requires both anxiogenic stimulus and social familiarity during training sessions (5-6 daily SI sessions), and SoFiA expression is dependent on infralimbic subdivision (IL) of the ventromedial prefrontal cortex and the basolateral amygdala (BLA). Here we investigated the role of IL in SoFiA acquisition and expression, using chemogenetics to inhibit IL neurons. Male Wistar rats received bilateral viral injections targeting the IL or BLA and left undisturbed for 5-7 weeks to allow for viral expression. We chemogenetically inhibited via low doses of ip. clozapine-N-oxide (CNO) either the IL, the BLA, or the projections neurons from the IL to the BLA during expression of SoFiA in rats. We found that projection neurons from IL to the BLA are critical for the recovery SI behavior from the attenuation caused by the bright light (expression of SoFiA). Furthermore, CNO inhibited IL neurons with projections to the BLA and there were no off target effects of CNO on the behavioral measures. These results suggest an essential role of the IL-BLA pathway in social safety learning.
Significance Statement: The proposed research is relevant to public health because it will increase our systematic/mechanistic understanding of how social support improves the ability to manage anxiety responses, which will provide novel insights into our understanding of cognitive control of emotional behaviors. Impairments in social behaviors are the most prominent and disabling features of mental illness. This research will lead to increased understanding of the neural regulation of behavior and provide insights into ways to eventually reduce the burden of mental illness.
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BibTeX
@misc{majumdar2026projection,
title = {{Projection Neurons from Infralimbic (IL) to the Basolateral Amygdala (BLA) are Critical for the Expression of Social Familiarity induced Anxiolysis (SoFiA) in rats}},
author = {Sreeparna Majumdar and Andrew R Burke and Erik T. Dustrude and Elizabeth A. Lungwitz and Katharine D. Andrews and Amy D Dietrich and William A. Truitt},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.27.762180},
url = {https://www.biorxiv.org/content/10.64898/2026.10.27.762180v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Projection Neurons from Infralimbic (IL) to the Basolateral Amygdala (BLA) are Critical for the Expression of Social Familiarity induced Anxiolysis (SoFiA) in rats
AU - Sreeparna Majumdar
AU - Andrew R Burke
AU - Erik T. Dustrude
AU - Elizabeth A. Lungwitz
AU - Katharine D. Andrews
AU - Amy D Dietrich
AU - William A. Truitt
PY - 2026
DA - 2026/10/27
PB - bioRxiv
DO - 10.64898/2026.10.27.762180
UR - https://www.biorxiv.org/content/10.64898/2026.10.27.762180v1
AB - Mental health is crucially linked to social behavior. Healthy social behavior involves learning to adapt emotional responses to social cues, for example learning to suppress anxiety through social familiarity, or social familiarity-induced anxiolysis (SoFiA). SoFiA is well documented and forms the basis for interpersonal therapy, however, the neural mechanisms of SoFiA are unclear. SoFiA is modeled in rats by employing the social interaction habituation (SI-hab) protocol. Using SI-hab protocol, it has been determined that SoFiA represents social safety learning, which requires both anxiogenic stimulus and social familiarity during training sessions (5-6 daily SI sessions), and SoFiA expression is dependent on infralimbic subdivision (IL) of the ventromedial prefrontal cortex and the basolateral amygdala (BLA). Here we investigated the role of IL in SoFiA acquisition and expression, using chemogenetics to inhibit IL neurons. Male Wistar rats received bilateral viral injections targeting the IL or BLA and left undisturbed for 5-7 weeks to allow for viral expression. We chemogenetically inhibited via low doses of ip. clozapine-N-oxide (CNO) either the IL, the BLA, or the projections neurons from the IL to the BLA during expression of SoFiA in rats. We found that projection neurons from IL to the BLA are critical for the recovery SI behavior from the attenuation caused by the bright light (expression of SoFiA). Furthermore, CNO inhibited IL neurons with projections to the BLA and there were no off target effects of CNO on the behavioral measures. These results suggest an essential role of the IL-BLA pathway in social safety learning. Significance Statement: The proposed research is relevant to public health because it will increase our systematic/mechanistic understanding of how social support improves the ability to manage anxiety responses, which will provide novel insights into our understanding of cognitive control of emotional behaviors. Impairments in social behaviors are the most prominent and disabling features of mental illness. This research will lead to increased understanding of the neural regulation of behavior and provide insights into ways to eventually reduce the burden of mental illness.
SN - 2692-8205
ER -