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.

研究的长期目标是增加我们对 突触传播的调节和调节方式。提议 研究将检查兴奋性的单突触连接 APLYSIA的大脑神经节中的A和B神经元。低频 刺激（<0.01 Hz） 突触前A神经元的神经元诱导明显的突触抑制。这 拟议的研究将阐明生化和生物物理 介导抑郁的机制。实验将使用电压夹 从突触前A神经元记录以测量 突触抑郁症期间的膜电流。这将测试 假设抑郁是由于K+电流增加引起的 降低Ca2+电流，或两者兼而有之。循环放大器及其激活剂 减少EPSP振幅。该提议将检验以下假设 抑郁是由环状AMP介导的。膜电流变化 通过激活环状放大器诱导的诱导将与 低频射击。腺苷和腺苷激动剂也减少 EPSP振幅。该提案还将检验以下假设 突触抑制是由腺苷介导的。腺苷应产生 膜电流的变化与低频活性。 最后，A和B神经元上的腺苷受体将是 使用特定的腺苷A1和A2激动剂和 对手。这些研究将产生对细胞的见解 突触可塑性和活性依赖性的机制 突触传播的调节。