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D-氨酸的可用性调节前额叶皮层抑制性内部神经元发育和电路成熟.

Oluwarotimi O Folorunso1,2, Stephanie E Brown3, Jugajyoti Baruah3,4

  • 1Division of Basic Neuroscience, McLean Hospital, Belmont, MA, 02478, USA. ofolorunso@mclean.harvard.edu.

Scientific reports
|June 13, 2023
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概括

对于发展皮层内部神经元和维持大脑激发-抑制平衡而言,D-氨酸至关重要. 赛林赛马斯淘汰赛小鼠显示内部神经元发育和功能受损,突出显示D-赛林.

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科学领域:

  • 神经科学是一个神经科学.
  • 发育神经科学的发展神经科学.
  • 突触性可塑性 突触性可塑性

背景情况:

  • 皮层电路功能依赖于平衡的激发和抑制 (E/I),主要由GABAergic内部神经元介导.
  • 通过N-甲基-D-酸盐受体 (NMDARs) 传递谷氨酸信号对内部神经元发育至关重要.
  • 作为NMDARs的联合激动剂的D-氨酸是由氨酸赛马酶 (SR) 合成的.

研究的目的:

  • 调查D-氨酸可用性在皮质内神经元 (CIN) 和抑制性突触的发展中的作用.
  • 为了检查血清赛马酶缺乏对先皮质 (PrL) 产前和产后发育的影响.

主要方法:

  • 使用了构成性血清赛马斯淘汰赛 (SR-/-) 鼠标.
  • 分析了GABAergic内部神经元标记物 (Lhx6,GAD67,PV,Sst) 和NMDAR亚单元NR1的表达.
  • 在PrL中评估细胞增殖和突触功能 (抑制后突触潜力).

主要成果:

  • SR-/-小鼠在胚胎发育过程中表现出改变的GABA水平和质突出部的增多.
  • 在SR-/-小鼠的PrL中观察到GAD67+和帕瓦胺 (PV) +内部神经元密度的显著降低.
  • SR缺陷导致二三层金字塔神经元中抑制后突触潜能减少.

结论:

  • 对于皮层内部神经元的正常产前发育,D-氨酸的可用性至关重要.
  • 适当的D-氨酸水平对于产后皮质回路和突触功能的成熟至关重要.