Developmental Changes in Synaptic Distribution in Arcuate Nucleus Neurons
Developmental Changes in Synaptic Distribution in Arcuate Nucleus Neurons
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DOI：
10.1523/jneurosci.0058-15.2015
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发表时间：
2015-06-03
影响因子：
5.3
通讯作者：
Grove, Kevin L.
中科院分区：
文献类型：
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作者：
Baquero, Arian F.;Kirigiti, Melissa A.;Grove, Kevin L.
共表达神经肽Y、刺豚鼠相关肽和GABA（NAG）的神经元在摄食行为中起重要作用，位于下丘脑弓状核。NAG神经元接受GABA能和多巴胺能突触输入，但小鼠NAG神经元突触输入组织的发育时间过程尚不清楚。在这项研究中，我们发现，这些神经元有少量的GABA能突触，GABA是抑制NAG神经元在出生后早期。与此相反，NAG神经元的多巴胺能输入相对丰富的P13，并在成人中观察到的水平比较相似。随着小鼠成年（9-10周），NAG神经元上的GABA能张力增加。在这个年龄，NAG神经元接受了相似数量的抑制性和EPSC。为了进一步区分突触分布的年龄相关变化，研究了17至18周龄的瘦小鼠和饮食诱导的肥胖（DIO）小鼠。令人惊讶的是，与年轻的成年人相比，来自瘦的成年小鼠的NAG神经元表现出GABA能突触的减少。相反，DIO小鼠显示NAG神经元上的GABA能和谷氨酸能输入的数量减少。基于这些实验，我们提出NAG神经元的突触分布在整个发育过程中不断重组，以适应动物的能量需求。
Neurons coexpressing neuropeptide Y, agouti-related peptide, and GABA (NAG) play an important role in ingestive behavior and are located in the arcuate nucleus of the hypothalamus. NAG neurons receive both GABAergic and glutamatergic synaptic inputs, however, the developmental time course of synaptic input organization of NAG neurons in mice is unknown. In this study, we show that these neurons have low numbers of GABAergic synapses and that GABA is inhibitory to NAG neurons during early postnatal period. In contrast, glutamatergic inputs onto NAG neurons are relatively abundant by P13 and are comparatively similar to the levels observed in the adult. As mice reach adulthood (9-10 weeks), GABAergic tone onto NAG neurons increases. At this age, NAG neurons received similar numbers of inhibitory and EPSCs. To further differentiate age-associated changes in synaptic distribution, 17- to 18-week-old lean and diet-induced obesity (DIO) mice were studied. Surprisingly, NAG neurons from lean adult mice exhibit a reduction in the GABAergic synapses compared with younger adults. Conversely, DIO mice display reductions in the number of GABAergic and glutamatergic inputs onto NAG neurons. Based on these experiments, we propose that synaptic distribution in NAG neurons is continuously restructuring throughout development to accommodate the animals' energy requirements.