Consequences of sustained modulation of VIP-expressing neurons in mouse corticolimbic regions on anxiety-related avoidance behaviors, social functioning, and associative fear learning
- 1Mainz University Medical Center
Abstract
GABAergic inhibitory neurons play a central role in shaping network dynamics, and accordingly, their dysfunction is implicated in the pathophysiology of various psychiatric, neurodevelopmental, and neurological disorders. In the past decade, studies on vasoactive intestinal polypeptide-expressing inhibitory neurons (VIP+ neurons) have positioned them as critical components of this circuitry. In particular, VIP+ neurons have been proposed to function within a canonical disinhibitory circuit motif, preferentially inhibiting other interneuron subtypes, to ultimately modulate the gain and activity of local pyramidal neurons. However, their contribution to psychiatrically relevant behavioral endophenotypes is still not fully understood, limiting our ability to target these neurons for therapeutic purposes. In the present study, we systematically assessed the functional contribution of VIP+ neurons to affective and social behaviors. To this end, we used a chemogenetic approach to manipulate the activity of VIP+ neurons in core corticolimbic regions, including the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and ventral hippocampus (vHPC). The consequences of either activating or inhibiting VIP+ neurons in these regions were observed while mice underwent a battery of behavioral tasks assessing anxiety-related avoidance behaviors, social interest and recognition, and associative fear learning. While sustained modulation of VIP+ neurons had no significant effect on anxiety-related or social behaviors in any of the brain regions assessed, it produced a robust reduction in associative fear learning specifically in the mPFC. These findings demonstrate that the consequences of sustained VIP+ neuron modulation depend on both anatomical location and behavioural context. Moreover, they identify VIP+ neurons in the mPFC as potentially clinically relevant targets for interventions aimed at modulating fear-related circuits.
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BibTeX
@misc{taylor2026consequences,
title = {{Consequences of sustained modulation of VIP-expressing neurons in mouse corticolimbic regions on anxiety-related avoidance behaviors, social functioning, and associative fear learning}},
author = {M. Taylor and M. A. Nguyen and D. Pascual Cuadrado and Y. George and M. J. Schmeisser and J. Hesse and D. Krueger-Burg},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.30.755164},
url = {https://www.biorxiv.org/content/10.64898/2026.09.30.755164v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Consequences of sustained modulation of VIP-expressing neurons in mouse corticolimbic regions on anxiety-related avoidance behaviors, social functioning, and associative fear learning
AU - M. Taylor
AU - M. A. Nguyen
AU - D. Pascual Cuadrado
AU - Y. George
AU - M. J. Schmeisser
AU - J. Hesse
AU - D. Krueger-Burg
PY - 2026
DA - 2026/09/30
PB - bioRxiv
DO - 10.64898/2026.09.30.755164
UR - https://www.biorxiv.org/content/10.64898/2026.09.30.755164v1
AB - GABAergic inhibitory neurons play a central role in shaping network dynamics, and accordingly, their dysfunction is implicated in the pathophysiology of various psychiatric, neurodevelopmental, and neurological disorders. In the past decade, studies on vasoactive intestinal polypeptide-expressing inhibitory neurons (VIP+ neurons) have positioned them as critical components of this circuitry. In particular, VIP+ neurons have been proposed to function within a canonical disinhibitory circuit motif, preferentially inhibiting other interneuron subtypes, to ultimately modulate the gain and activity of local pyramidal neurons. However, their contribution to psychiatrically relevant behavioral endophenotypes is still not fully understood, limiting our ability to target these neurons for therapeutic purposes. In the present study, we systematically assessed the functional contribution of VIP+ neurons to affective and social behaviors. To this end, we used a chemogenetic approach to manipulate the activity of VIP+ neurons in core corticolimbic regions, including the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and ventral hippocampus (vHPC). The consequences of either activating or inhibiting VIP+ neurons in these regions were observed while mice underwent a battery of behavioral tasks assessing anxiety-related avoidance behaviors, social interest and recognition, and associative fear learning. While sustained modulation of VIP+ neurons had no significant effect on anxiety-related or social behaviors in any of the brain regions assessed, it produced a robust reduction in associative fear learning specifically in the mPFC. These findings demonstrate that the consequences of sustained VIP+ neuron modulation depend on both anatomical location and behavioural context. Moreover, they identify VIP+ neurons in the mPFC as potentially clinically relevant targets for interventions aimed at modulating fear-related circuits.
ER -