REGULATION OF SYNAPTIC DEPRESSION

突触抑制的调节

• 批准号: 6107049
• 负责人: STEVEN M FREDMAN
• 金额: $ 7.35万
• 依托单位: MEHARRY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6107049
• 关键词: Aplysia; G protein; adenosine; alternatives to animals in research; cyclic AMP; electrodes; ganglions; inhibitor /antagonist; membrane potentials; neural inhibition; neural plasticity; neural transmission; neurons; synapses; voltage /patch clamp

The long-term goal of the research is to increase our understanding of how synaptic transmission is modulated and regulated. The proposed research will examine excitatory monosynaptic connections between the A and B neurons in the cerebral ganglion of Aplysia. Low frequency stimulation (<0.01 Hz) of the presynaptic A neurons induces a marked synaptic depression. The proposed research will elucidate the biochemical and biophysical mechanisms mediating depression. The experiments will use voltage clamp recording from the presynaptic A neurons to measure the changes in membrane currents during synaptic depression. This will test the hypothesis that depression is due to an increase in K+ current, a decrease in Ca2+ current, or both. Cyclic AMP and its activators decrease EPSP amplitudes. The proposal will test the hypothesis that depression is mediated by cyclic AMP. The membrane current changes induced by activating cyclic AMP will be compared to those caused by low frequency firing. Adenosine and adenosine agonists also decrease EPSP amplitudes. The proposal will also test the hypothesis that synaptic depression is mediated by adenosine. Adenosine should produce the same changes in membrane current as low frequency activity. Finally, the adenosine receptors on the A and B neurons will be characterized using specific adenosine A1 and A2 agonists and antagonists. These studies will generate insights into the cellular mechanisms underlying synaptic plasticity and activity-dependent regulation of synaptic transmission.

这项研究的长期目标是加深我们对 突触传递是如何调节和调节的。拟议的 研究将检查兴奋性单突触之间的联系 海兔大脑神经节中的 A 和 B 神经元。低频 刺激（<0.01 Hz） 突触前 A 神经元的减少会引起明显的突触抑制。这 拟议的研究将阐明生物化学和生物物理 介导抑郁症的机制。实验将使用电压钳 记录突触前 A 神经元的变化 突触抑制期间的膜电流。这将测试 假设抑郁症是由于 K+ 电流增加造成的，a Ca2+ 电流减少，或两者兼而有之。环AMP及其激活剂 降低 EPSP 幅度。该提案将检验以下假设： 抑郁症是由环磷酸腺苷介导的。膜电流变化 由激活环AMP诱导的将与由 低频发射。腺苷和腺苷激动剂也减少 EPSP 幅度。该提案还将检验以下假设： 突触抑制是由腺苷介导的。腺苷应该产生 膜电流的变化与低频活动相同。 最后，A 和 B 神经元上的腺苷受体将被 使用特定的腺苷 A1 和 A2 激动剂进行表征， 对手。这些研究将深入了解细胞 突触可塑性和活动依赖性的潜在机制 突触传递的调节。