Direct innervation of GnRH neurons by metabolic- and sexual odorant-sensing leptin receptor neurons in the hypothalamic ventral premammillary nucleus.
Direct innervation of GnRH neurons by metabolic- and sexual odorant-sensing leptin receptor neurons in the hypothalamic ventral premammillary nucleus.
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DOI：
10.1523/jneurosci.0155-09.2009
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发表时间：
2009-03-11
期刊：
影响因子：
--
通讯作者：
Myers MG Jr
中科院分区：
文献类型：
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作者：
Leshan RL;Louis GW;Jo YH;Rhodes CJ;Münzberg H;Myers MG Jr
瘦素通过其受体（LepRb）作用于特定的中枢神经系统神经元，以发出长期能量储存充足的信号，从而允许将资源消耗在能量密集型过程（如生殖）上。腹侧前乳头体核的下丘脑（PMV），这已牵连在刺激促性腺激素释放的嗅觉线索，含有大量的LepRb神经元，这表明LepRb PMV神经元在传递代谢和气味信号的神经内分泌生殖系统的潜在作用。事实上，Fos-免疫反应（-IR）和电生理记录显示瘦素直接激活LepRb PMV神经元，暴露于气味从小鼠的异性促进Fos-IR在许多LepRb PMV神经元。为了确定由LepRb PMV神经元支配的区域，我们利用了两个新的CREE激活的跟踪系统在麻风动物;从这些系统和标准的跟踪技术的数据显示，LepRb PMV神经元项目的一个子集的区域，包括视前区（POA），这是由PMV作为一个整体支配。此外，在LepRb PMv神经元的跨突触示踪剂从GnRH神经元的逆行积累揭示了许多LepRb PMv神经元的GnRH神经元的直接神经支配。因此，LepRb PMv神经元感知代谢和性气味线索，并投射到吻侧下丘脑以直接支配GnRH神经元。这些结果与LepRb PMV神经元在调节生殖轴代谢和气味刺激的作用是一致的。
Leptin acts via its receptor (LepRb) on specific CNS neurons to signal the adequacy of long-term energy stores, thereby permitting the expenditure of resources on energy-intensive processes such as reproduction. The ventral premammillary nucleus of the hypothalamus (PMv), which has been implicated in the stimulation of gonadotropin release by olfactory cues, contains numerous LepRb neurons, suggesting a potential role for LepRb PMv neurons in transmitting both metabolic and odorant signals to the neuroendocrine reproductive system. Indeed, Fos-immunoreactivity (-IR) and electrophysiologic recordings revealed the direct activation of LepRb PMv neurons by leptin, and exposure to odors from mice of the opposite sex promoted Fos-IR in many LepRb PMv neurons. To determine the regions innervated by the LepRb PMv neurons, we utilized two novel cre-activated tract-tracing systems in Leprcre animals; data from these systems and from standard tracing techniques revealed that LepRb PMv neurons project to a subset of the regions, including the preoptic area (POA), that are innervated by the PMv as a whole. Furthermore, the retrograde accumulation in LepRb PMv neurons of a trans-synaptic tracer from GnRH neurons revealed the direct innervation of GnRH neurons by many LepRb PMv neurons. Thus, LepRb PMv neurons sense metabolic and sexual odorant cues and project to the rostral hypothalamus to directly innervate GnRH neurons. These results are consistent with a role for LepRb PMv neurons in regulating the reproductive axis in response to metabolic and odorant stimuli.