Oxytocin signaling bidirectionally modulates serotonergic and dopaminergic neurons in the dorsal raphe nucleus
Abstract
The involvement of oxytocin in social behavior is well established, yet its interaction with neuromodulatory systems, such as serotonin and dopamine, remains incompletely understood. Here, we utilized immunohistochemistry, anatomical tracing, chemogenetic, and ex vivo electrophysiological approaches primarily in male mice, with female mice used only for an additional anatomical tracing control experiment, investigate how oxytocin modulates serotonergic and dopaminergic neuronal populations. Employing the dual-eGRASP tool, we visualized oxytocinergic projections from the paraventricular nucleus (PVN) to the serotonergic and dopaminergic neurons in dorsal raphe nucleus (DRN). Blocking oxytocin receptors in the DRN attenuated social interaction behavior. Additionally, analysis of c-Fos levels and neuronal excitability revealed that oxytocin inhibits serotonergic neurons while activating dopaminergic neurons in the DRN. Our findings suggest a bidirectional regulatory role of oxytocin signaling in the DRN serotonergic and dopaminergic neurons.
Significance Statement Social behavior relies on interactions among neuromodulatory systems, yet how oxytocin communicates with serotonin and dopamine circuits remains unclear. We identify the DRN as a functionally relevant target of hypothalamic oxytocin neurons during social approach. Using dual-eGRASP, we visualize contacts from PVN oxytocin neurons onto both serotonergic and dopaminergic DRN. Blocking oxytocin receptors in the DRN reduces social interaction without affecting locomotion. Moreover, oxytocin suppresses serotonergic neuronal activity while increasing dopaminergic neuronal activation, revealing opposing control of two prosocial neuromodulatory populations within the same region. These findings provide a circuit framework for how oxytocin coordinates social behavior through bidirectional modulation of dorsal raphe neuromodulators.
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BibTeX
@article{choi2026oxytocin,
title = {{Oxytocin signaling bidirectionally modulates serotonergic and dopaminergic neurons in the dorsal raphe nucleus}},
author = {Ja Eun Choi and Yoon Kyoung Kim and Yongmin Sung and Dong Il Choi and Jooyoung Kim and Chaery Lee and Jisu Lee and Nam-Kyung Yu and Han Kyoung Choe and Bong-Kiun Kaang},
journal = {eneuro},
year = {2026},
month = oct,
doi = {10.1523/eneuro.0182-26.2026},
url = {https://www.eneuro.org/lookup/doi/10.1523/ENEURO.0182-26.2026},
note = {CC BY-NC-SA 4.0},
}
RIS
TY - JOUR
TI - Oxytocin signaling bidirectionally modulates serotonergic and dopaminergic neurons in the dorsal raphe nucleus
AU - Ja Eun Choi
AU - Yoon Kyoung Kim
AU - Yongmin Sung
AU - Dong Il Choi
AU - Jooyoung Kim
AU - Chaery Lee
AU - Jisu Lee
AU - Nam-Kyung Yu
AU - Han Kyoung Choe
AU - Bong-Kiun Kaang
PY - 2026
DA - 2026/10/16
JO - eneuro
DO - 10.1523/eneuro.0182-26.2026
UR - https://www.eneuro.org/lookup/doi/10.1523/ENEURO.0182-26.2026
AB - The involvement of oxytocin in social behavior is well established, yet its interaction with neuromodulatory systems, such as serotonin and dopamine, remains incompletely understood. Here, we utilized immunohistochemistry, anatomical tracing, chemogenetic, and ex vivo electrophysiological approaches primarily in male mice, with female mice used only for an additional anatomical tracing control experiment, investigate how oxytocin modulates serotonergic and dopaminergic neuronal populations. Employing the dual-eGRASP tool, we visualized oxytocinergic projections from the paraventricular nucleus (PVN) to the serotonergic and dopaminergic neurons in dorsal raphe nucleus (DRN). Blocking oxytocin receptors in the DRN attenuated social interaction behavior. Additionally, analysis of c-Fos levels and neuronal excitability revealed that oxytocin inhibits serotonergic neurons while activating dopaminergic neurons in the DRN. Our findings suggest a bidirectional regulatory role of oxytocin signaling in the DRN serotonergic and dopaminergic neurons. Significance Statement Social behavior relies on interactions among neuromodulatory systems, yet how oxytocin communicates with serotonin and dopamine circuits remains unclear. We identify the DRN as a functionally relevant target of hypothalamic oxytocin neurons during social approach. Using dual-eGRASP, we visualize contacts from PVN oxytocin neurons onto both serotonergic and dopaminergic DRN. Blocking oxytocin receptors in the DRN reduces social interaction without affecting locomotion. Moreover, oxytocin suppresses serotonergic neuronal activity while increasing dopaminergic neuronal activation, revealing opposing control of two prosocial neuromodulatory populations within the same region. These findings provide a circuit framework for how oxytocin coordinates social behavior through bidirectional modulation of dorsal raphe neuromodulators.
SN - 2373-2822
ER -