Yan‑Chu‑Fei Zhang1,2,3 · Qing‑Wu Zheng1,2,3 · Yang Lu1,2,3 · Hao‑Yuan Wang1,2,3 · Jiao Cang1,2,3 · Xin‑Rui Wu1  · Lin‑Yao Fan1,2,3 · Liang Li1,2,3  · Ni‑Na Zhang4  · Xiao‑Yang Zhang1,2  · Jing‑Ning Zhu1,2,5  · Jian Jing1,2,3  · Qi‑Peng Zhang1,2,3,4

1 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China 

2 Institute for Brain Sciences, Nanjing University, Nanjing 210023, China 

3 Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), Nanjing 210023, China 

4 Department of Gastroenterology, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, Nanjing 210023, China 

5 Chemistry and Biomedicine Innovation Center (ChemBIC), ChemBioMed Interdisciplinary Research Center, Nanjing University, Nanjing 210023, China

Abstract

Yawning coupled with penile erection is a conserved neurobehavioral syndrome mediated by the paraventricular hypothalamus (PVH). However, the distinct roles of oxytocin and its co-transmitters remain unresolved. Using chemogenetics, we showed that activation of PVH oxytocin neurons was sufficient to elicit both responses, whereas silencing these neurons abolished them. Viral tracing revealed that these neurons project collaterally to the brainstem reticular nucleus and spinal cord to spatially coordinate autonomic and somatic motor outputs. By dissecting the molecular mechanisms using CRISPR-Cas9, we found that vesicular glutamate transporter 2 (VGLUT2)-dependent glutamatergic transmission provides the primary drive for both behaviors, whereas the oxytocin peptide is selectively required for yawning but dispensable for erection. Comparative analyses across rats, hamsters, and mice demonstrated that while the glutamatergic erectile circuit was conserved, mice lacked spontaneous yawning and were resistant to apomorphine-induced yawning. These findings suggest a hierarchical co-transmission framework in which fast glutamatergic signaling provides the core drive, while oxytocin confers behavioral specificity.

Keywords

Oxytocin; Glutamate; Yawn; Penile erection; Rodents

[SpringerLink]