生物
突触
突触后电位
神经科学
突触可塑性
兴奋性突触
神经突
神经营养因子
谷氨酸的
作者
Gulcan Semra Sahin,Jose Luis Rodriguez-Llamas,Crystal Dillon,Igor Medina,Suzanne M. Appleyard,Jean-Luc Gaiarsa,Gary A. Wayman
出处
期刊:Science Signaling
[American Association for the Advancement of Science (AAAS)]
日期:2021-05-18
卷期号:14 (683)
被引量:1
标识
DOI:10.1126/scisignal.abe4111
摘要
Developing hippocampal neurons undergo rapid synaptogenesis in response to neurotrophic signals to form and refine circuit connections. The adipokine leptin is a satiety factor with neurotrophic actions, which potentiates both glutamatergic and GABAergic synaptogenesis in the hippocampus during neonatal development. Brief exposure to leptin enhances GABAA receptor-dependent synaptic currents in hippocampal neurons. Here, using molecular and electrophysiological techniques, we found that leptin increased the surface localization of GABAA receptors and the number of functional GABAergic synapses in hippocampal cultures from male and female rat pups. Leptin increased the interaction between GABAA receptors and the Rho guanine exchange factor β-PIX (a scaffolding protein at GABAergic postsynaptic sites) in a manner dependent on the kinase CaMKK. We also found that the leptin receptor and β-PIX formed a complex, the amount of which transiently increased upon leptin receptor activation. Furthermore, Tyr985 in the leptin receptor and the SH3 domain of β-PIX are crucial for this interaction, which was required for the developmental increase in GABAergic synaptogenesis. Our results suggest a mechanism by which leptin promotes GABAergic synaptogenesis in hippocampal neurons and reveal further complexity in leptin receptor signaling and its interactome.
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