Shenzhen Key Lab of Neuropsychiatric Modulation, Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, the Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, China.
University of the Chinese Academy of Sciences, Beijing, 100049, China.
Neurosci Bull. 2022 Dec;38(12):1439-1456. doi: 10.1007/s12264-022-00885-y. Epub 2022 May 29.
The lateral habenula (LHb), which is a critical neuroanatomical hub and a regulator of midbrain monoaminergic centers, is activated by events resulting in negative valence and contributes to the expression of both appetitive and aversive behaviors. However, whole-brain cell-type-specific monosynaptic inputs to the LHb in both sexes remain incompletely elucidated. In this study, we used viral tracing combined with in situ hybridization targeting vesicular glutamate transporter 2 (vGlut2) and glutamic acid decarboxylase 2 (Gad2) to generate a comprehensive whole-brain atlas of inputs to glutamatergic and γ-aminobutyric acid (GABA)ergic neurons in the LHb. We found >30 ipsilateral and contralateral brain regions that projected to the LHb. Of these, there were significantly more monosynaptic LHb-projecting neurons from the lateral septum, anterior hypothalamus, dorsomedial hypothalamus, and ventromedial hypothalamus in females than in males. More interestingly, we found a stronger GABAergic projection from the medial septum to the LHb in males than in females. Our results reveal a comprehensive connectivity atlas of glutamatergic and GABAergic inputs to the LHb in both sexes, which may facilitate a better understanding of sexual dimorphism in physiological and pathological brain functions.
外侧缰核（LHb）是一个关键的神经解剖学中枢，调节中脑单胺能中心，它被导致负效价的事件激活，并有助于表达食欲和厌恶行为。然而，两性中 LHb 的全脑细胞类型特异性单突触输入仍不完全清楚。在这项研究中，我们使用病毒追踪结合针对囊泡谷氨酸转运体 2（vGlut2）和谷氨酸脱羧酶 2（Gad2）的原位杂交，生成了 LHb 中谷氨酸能和γ-氨基丁酸（GABA）能神经元全脑输入的综合图谱。我们发现了>30 个同侧和对侧的投射到 LHb 的脑区。其中，来自外侧隔核、前下丘脑、下丘脑背内侧核和下丘脑腹内侧核的 LHb 投射神经元在女性中明显多于男性。更有趣的是，我们发现雄性中来自内侧隔核的 LHb 的 GABA 能投射比雌性更强。我们的结果揭示了两性 LHb 的谷氨酸能和 GABA 能输入的综合连接图谱，这可能有助于更好地理解生理和病理脑功能中的性别二态性。
