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Organizations and postnatal maturation of local neuronal networks of the nucleus of tractus solitairus

孤束核局部神经元网络的组织和出生后成熟

基本信息

批准号：
12680780
负责人：
KAWAI Yoshinori
金额：
$ 1.73万
依托单位：
Wakayama Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12680780/
关键词：
Nucleus of tractus solitarins GABA Local network Synapse elimination Receptor Cardiovascular Respiratory

项目摘要

γ-aminobutyric acid (GABA) is a main inhibitory neurotransmitter in the central nervous system and thought to be critically involved in regulating excitatory neurotransmission. For the inhibitory neurotransmission, GABAA receptors, a pentameric hetero-oligomer ligand-gated chloride channel consisting mainly of α,β and γ subunits, must be clustered at the postsynaptic membranes. In the present study, how GABAergic synaptic activity and expression of molecules responsible for the receptor-mediated transmission are regulated and correlated with each other during development,was addressed in the nucleus of the tractus solitarius (NTS). GABAergic inhibitory postsynaptic currents (IPSCs) and expression of GABAA receptqrγ1-subunit, which is essential for the receptor clustering at the postsynaptic membranes, were consistently evident in small sized neurons of the caudal NTS during the early postnatal period (P1-6). After the first postnatal week, both IPSCs and expression of GABAA receptorγ1-subunit virtually disappeared in these neurons. Low level expression of GABAA receptorγ2-subunit and gephyrin were consistently observed in the NTS. Electron microscopy revealed that numbers of GABAergic axosomatic synapses were decreased and virtually disappeared during the development. These results show that GABAergic synaptic activity and γ1 subunit expression were closely associated with each other and that they are developmentally regulated in specific type of NTS neurons for an establishment of mei local neuronal networks of adult type. This phenomenon may underlie an establishment of cardiovascular and respiratory reflex circuits in the medulla.

γ-氨基丁酸（γ-aminobutyric acid，GABA）是中枢神经系统中主要的抑制性神经递质，在兴奋性神经递质的调节中起重要作用。为了抑制神经传递，GABAA受体，一种主要由α、β和γ亚基组成的五聚体异寡聚体配体门控氯通道，必须聚集在突触后膜上。在本研究中，GABA能突触活动和负责受体介导的传输的分子的表达是如何调节和相互关联的发展过程中，在孤束核（NTS）的解决。在出生后早期（P1-6），尾侧孤束核的小型神经元持续出现GABA能抑制性突触后电流（IPSC）和GABAA受体γ1亚单位的表达，这是受体聚集在突触后膜上所必需的。出生后第1周，IPSC和GABAA受体γ1亚单位的表达几乎消失。孤束核GABAA受体γ2亚单位和桥蛋白的表达均较低。电子显微镜观察发现，GABA能轴体突触的数量在发育过程中减少，甚至消失。这些结果表明，GABA能突触活动和γ1亚单位表达密切相关，它们在特定类型的NTS神经元中受到发育调节，以建立成年型的局部神经元网络。这种现象可能是延髓中心血管和呼吸反射回路建立的基础。