Medial Preoptic Area Modulates Courtship Ultrasonic Vocalization in Adult Male Mice / 神经科学通报·英文版

Adult male mice emit highly complex ultrasonic vocalizations (USVs) in response to female conspecifics. Such USVs, thought to facilitate courtship behaviors, are routinely measured as a behavioral index in mouse models of neurodevelopmental and psychiatric disorders such as autism. While the regulation of USVs by genetic factors has been extensively characterized, the neural mechanisms that control USV production remain largely unknown. Here, we report that optogenetic activation of the medial preoptic area (mPOA) elicited the production of USVs that were acoustically similar to courtship USVs in adult mice. Moreover, mPOA vesicular GABA transporter-positive (Vgat +) neurons were more effective at driving USV production than vesicular glutamate transporter 2-positive neurons. Furthermore, ablation of mPOA Vgat+ neurons resulted in altered spectral features and syllable usage of USVs in targeted males. Together, these results demonstrate that the mPOA plays a crucial role in modulating courtship USVs and this may serve as an entry point for future dissection of the neural circuitry underlying USV production.

Wnt1/β-catenin signaling up-regulates spinal VGLUT2 expression to maintain neuropathic pain in mice / 中国药理学与毒理学杂志

OBJECTIVE The present study was aimed to investigate the role of Wnt/β-catenin sig-naling in spinal VGLUT2 regulation and neuropathic pain. METHODS To elucidate the association be-tween VGLUT2 and neuropathic pain,we determined the expression and distribution characteristics of VGLUT2 in mice subjected to spared nerve injury(SNI),and then observed the effects of two VGLUT2 targeting shRNAs on mechanical allodynia and glutamate release.The effects of Wnt/β-catenin signal-ing on VGLUT2 expression and pain behavior were investigated by using Wnt agonist,Wnt1,and Wnt/β-catenin pathway inhibitor XAV939 in SNI mice.RESULTS SNI surgery induced significant up-regula-tion of VGLUT2 on postoperative days 7,14,and 21.Double immunofluorescence labeling of VGLUT2 with NeuN,MAP2,Iba-1,or GFAP showed that VGLUT2 was mainly expressed in neurons in the dor-sal horn of the spinal cord after SNI(NeuN,MAP2).Intrathecal administration of VGLUT2 shRNAs be-fore or after SNI surgery significantly decreased mechanical allodynia and glutamate release. Mean-while,Wnt1/β-catenin signaling increased significantly after SNI surgery.Over-expression of β-catenin in PC12 cells increased VGLUT2 protein level,intrathecal administration of Wnt agonist or Wnt1 signifi-cantly increased VGLUT2 protein expression in spinal cord, while Wnt/β-catenin pathway inhibitor XAV939 decreased VGLUT2 expression in PC12 cells and spinal cord.Additionally,intrathecal admin-istration of XAV939 7 days after SNI significantly attenuated mechanical allodynia in mice, which was in accordance with down-regulation of VGLUT2 protein levels.VGLUT2 shRNAs significantly attenuat-ed Wnt agonist or Wnt1 induced mechanical allodynia. CONCLUSION Wnt1/β-catenin signaling path-way up-regu-lates the spinal VGLUT2 expression,and this regulation is involved in neuropathic pain behavior.

DISTRIBUTION OF VGluT1 AND VGluT2 IN THE SPINAL CORD IN DIFFERENT MAMMALIAN SPECIES: RAT, CAT AND MONKEY / 解剖学报

Objective To investigate the distribution of the vesicular glutamate transporters (VGluTs), VGIuT1 and VGIuT2, in the spinal cord in multiple species, including rat, cat and monkey. Methods An immunohistochemical technique was used in the present study. Results VGluTs were observed in the gray matter of the spinal cord of rat, cat and monkey. VGluTl-immunoreactivity (VGluT1-IR) was most intense in the inner part of lamina Ⅱ(Ⅱi) and the medial parts of laminae Ⅲ-Ⅵ of the spinal dorsal horn; weak in lamina Ⅰ and outer part of lamina Ⅱ(Ⅱo); moderate in other parts in the rat and cat. The laminar distribution of VGluT1-IR in the spinal cord in the monkey is different from those in the rat and cat. The VGluT1-immunopositive product was intense in laminae Ⅰ, Ⅱi, Ⅲ and the medial parts of laminae Ⅳ-Ⅵ of the spinal dorsal horn; weak to absent in lamina Ⅱo and the lateral parts of laminae Ⅳ-Ⅵ of the dorsal horn. In the spinal anterior horn of monkey, the VGluT1-immunoreactive profiles were observed sparsely just in lamina Ⅸ, not in other laminae. At the same time, some scattered immunoreactive profiles were present in the white matter, particularly at the medial parts of the dorsal column in monkey, but not in rat and cat. On the other hand, VGluT2 immunoreactivity (VGluT2-IR) was moderately present throughout the gray matter, it was most dense in laminae Ⅰ-Ⅱ and Ⅹ, and weak in the medial parts of the deep spinal dorsal horn (laminae Ⅲ-Ⅵ) in the three species. The VGluT2-immunopositive product was very sparse in the lateral parts of the deep spinal dorsal horn of the monkey. In the lateral spinal nuclei of the rat, moderate VGluT2-immunopositive product could be seen, but not in the cat and monkey. In three species, both VGluT1- and VGluT2-IR showed a punctuate distribution. Conclusion The present results indicated that VGluT1 and VGluT2 were expressed in the spinal cord in all species examined but differentially distributed in a species-specific manner, and they might play an important role in the activities of the excitatory neurons in the spinal cord of rat, cat and monkey.