• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Regulation of excitability and plasticity by endocannabinoids and PKA in developing hippocampus
【24h】

Regulation of excitability and plasticity by endocannabinoids and PKA in developing hippocampus

机译：内源性大麻素和PKA对发育中的海马的兴奋性和可塑性的调节

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The activity-dependent strengthening and weakening of synaptic transmission are hypothesized to be the basis of not only memory and learning but also the refinement of neural circuits during development. Here we report that, in the developing CA1 area of the hippocampus, endocannabinoid (eCB)-mediated heterosynap-tic long-term depression (LTD) of glutamatergic excitatory synaptic transmission is associated with PKA-mediated homosynaptic long-term potentiation (LTP). This form of LTD was dominant at postnatal days 2-10 (P2-P10), attenuated during development, and finally disappeared in the mature hippocampus. Heterosynaptic LTD of excitatory postsynaptic currents in the developing hippocampus was expressed presynaptically, spread to neighboring neurons, and was mediated by eCBs. Heterosynaptic LTD of field excitatory postsynaptic potentials was associated with a decrease in fiber volley amplitude with a similar time course. Depression of fiber volleys was blocked by K~+ channel blockers, suggesting the involvement of the decrease in presynaptic excitability in heterosynaptic LTD. In the P2-P5 hippocampus, eCBs also attenuate LTP and fiber volleys in homosynaptic pathways and help to prevent too much excitability in the neonatal hippocampus where the GABAergic system is poorly developed and even excitatory. In the hippocampus older than P6 (P > 6), however, LTP is protected from eCB-mediated depression by PKA activated at presynaptic sites by high-frequency stimulation, serving to highlight PKA-mediated LTP by weakening inactive synapses even in adjacent cells. Thus, eCBs and PKA make synapses plastic without changing excitability homeostasis in the developing hippocampus.
机译：假定活动依赖的突触传递的增强和减弱不仅是记忆和学习的基础，而且是发育过程中神经回路细化的基础。在这里，我们报告说，在海马的CA1发育区域，内源性大麻素（eCB）介导的谷氨酸能兴奋性突触传递的异质突触长期抑制（LTD）与PKA介导的同质突触长期增强（LTP）相关。这种形式的LTD在产后2-10天（P2-P10）占优势，在发育过程中减弱，最后在成熟的海马体中消失。发育中的海马中兴奋性突触后电流的异突触LTD被突触前表达，扩散到邻近的神经元，并由eCBs介导。场兴奋性突触后电位的异突触有限公司与纤维齐射幅值的减少具有相似的时间过程。纤维齐射的抑制被K〜+通道阻滞剂阻​​滞，提示异突触LTD中突触前兴奋性的降低。在P2-P5海马中，eCBs还会减弱同源突触途径中的LTP和纤维齐射，并有助于防止新生的海马中过多的兴奋性，而新生的海马中GABA能系统发育不良甚至是兴奋性的。然而，在年龄大于P6的海马中（P> 6），通过高频刺激在突触前位点激活的PKA保护LTP免受eCB介导的抑郁，从而通过削弱即使在相邻细胞中的无活性突触来突出PKA介导的LTP。因此，eCB和PKA使突触可塑性，而不会改变发育中的海马体的兴奋性稳态。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号