BDNF-TrkB signaling in oxytocin neurons contributes to maternal behavior

Brain-derived neurotrophic factor (Bdnf) transcription is controlled by several promoters, which drive expression of multiple transcripts encoding an identical protein. We previously reported that BDNF derived from promoters I and II is highly expressed in hypothalamus and is critical for regulating aggression in male mice. Here we report that BDNF loss from these promoters causes reduced sexual receptivity and impaired maternal care in female mice, which is concomitant with decreased oxytocin (Oxt) expression during development. We identify a novel link between BDNF signaling, oxytocin, and maternal behavior by demonstrating that ablation of TrkB selectively in OXT neurons partially recapitulates maternal care impairments observed in BDNF-deficient females. Using translating ribosome affinity purification and RNA-sequencing we define a molecular profile for OXT neurons and delineate how BDNF signaling impacts gene pathways critical for structural and functional plasticity. Our findings highlight BDNF as a modulator of sexually-dimorphic hypothalamic circuits that govern female-typical behaviors.脑源性神经营养因子（Brain-derived neurotrophic factor，Bdnf）的转录由多个启动子调控，这些启动子可驱动表达多种编码同一蛋白质的转录本。我们此前的研究表明，源自启动子I和II的脑源性神经营养因子在下丘脑呈高表达状态，且对调控雄性小鼠的攻击行为至关重要。本研究发现，缺失上述启动子介导的脑源性神经营养因子表达会导致雌性小鼠的性接受能力降低、母性行为受损，这一表型与发育过程中催产素（Oxytocin，Oxt）的表达下调相伴发生。我们通过实验证实，选择性敲除催产素能神经元中的酪氨酸激酶受体B（TrkB）可部分重现脑源性神经营养因子缺陷雌性小鼠的母性行为损伤表型，由此揭示了脑源性神经营养因子信号通路、催产素与母性行为之间的全新关联。本研究利用翻译核糖体亲和纯化（translating ribosome affinity purification）与RNA测序（RNA-sequencing）技术，明确了催产素能神经元的分子特征，并阐明了脑源性神经营养因子信号通路如何调控与结构及功能可塑性密切相关的基因通路。本研究结果显示，脑源性神经营养因子是调控雌性典型行为的性二态性下丘脑环路的关键调节因子。