Regulation of photoreceptor neurotransmission

感光神经传递的调节

• 批准号: 7281181
• 负责人: WALLACE B THORESON
• 金额: $ 28.55万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-15 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7281181
• 关键词: Action Potentials; Address; Affinity; Catabolism; Cells; Chromosome Pairing; Cleaved cell; Condition; Coupling; Darkness; Electric Capacitance; Elevation; Enzymes; Exhibits; Exocytosis; Functional disorder; Glutamate Receptor; Glutamate-Ammonia Ligase; Glutamates; Individual; Ischemia; Kynurenic Acid; Light; Lighting; Measurement; Measures; Membrane Potentials; Methods; Neurons; Photoreceptors; Physiological; Process; Property; Regulation; Relative (related person); Resistance; Retina; Retinal Cone; Series; Sum; Synapses; Synaptic Cleft; Synaptic Transmission; Synaptic Vesicles; Techniques; Testing; Vertebrate Photoreceptors; Vesicle; Visual Pathways; Whole-Cell Recordings; cell type; concept; desensitization; electrical property; horizontal cell; neurotransmission; postsynaptic; presynaptic; quantum; receptor; research study; response; retinal neuron; retinal rods; transmission process; transport inhibitor; visual information

DESCRIPTION (provided by applicant): Unlike most other CNS neurons, photoreceptors have a relatively depolarized resting potential in darkness, exhibit graded hyperpolarizing responses to light, and do not usually generate action potentials. To accommodate the graded responses of rods and cones it has been suggested that mechanisms of synaptic transmission from rods and cones also differ from those at other CNS neurons. At most CNS neurons, post-synaptic responses reflect the summed actions of independent miniature excitatory post-synaptic currents (mEPSCs) each arising from fusion of single synaptic vesicles that briefly elevate glutamate in the immediately adjoining synaptic cleft to high concentrations (>1 mM). In contrast, it has been suggested that post-synaptic responses at the photoreceptor synapse may be determined by spatially integrated levels of glutamate in the synaptic cleft. The proposal distinguishes between these two possibilities using simultaneous whole cell recordings from photoreceptors and post-synaptic neurons as well as capacitance techniques for measuring exocytosis. In addition to defining the relationship between exocytosis and postsynaptic responses at the photoreceptor synapse, the proposed experiments will analyze glutamate levels in the synaptic cleft and the impact of these levels on glutamate receptor desensitization, differences between glutamate receptors in OFF-type bipolar cells and horizontal cells contacted by rods vs. cones, and properties of mEPSCs in horizontal and OFF bipolar cells. If the quantal post-synaptic actions of vesicles are found to largely determine responses of second order retinal neurons, then evoked post-synaptic currents will be deconvolved into their individual quanta and used to determine release parameters under different physiological conditions such as changing levels of illumination. In addition to understanding how visual information is transformed across the first synapse in the visual pathway, the proposed experiments on the regulation of glutamate release by photoreceptors are also important for understanding pathophysiology in the retina since increased glutamate release (e.g., accompanying ischemia) can have excitotoxic consequences on post-synaptic neurons.

描述（由申请人提供）：与大多数其他中枢神经系统神经元不同，光感受器在黑暗中具有相对去极化的静息潜力，表现出对光的分级超极化反应，并且通常不会产生动作电位。为了适应棒和锥体的分级响应，已经提出，棒和锥的突触传递机制也与其他CNS神经元的机制也不同。在大多数中枢神经系统神经元中，突触后反应反映了独立微型兴奋性兴奋性后突触电流（MEPSC）的总结作用，这是由单个突触囊泡融合而产生的，这些突触囊泡融合了单个突触囊泡，这些突触囊泡在紧密升高的突触裂缝中短暂升高到高浓度（> 1 mm）。相比之下，已经提出，光感受器突触处的突触后反应可以通过突触裂口中的空间整合谷氨酸水平来确定。该提案区分了这两种可能性，同时使用全细胞记录与光感受器和突触后神经元以及用于测量胞吐作用的电容技术。 In addition to defining the relationship between exocytosis and postsynaptic responses at the photoreceptor synapse, the proposed experiments will analyze glutamate levels in the synaptic cleft and the impact of these levels on glutamate receptor desensitization, differences between glutamate receptors in OFF-type bipolar cells and horizo​​ntal cells contacted by rods vs. cones, and properties of mEPSCs in horizo​​ntal and OFF双极细胞。如果发现囊泡的量化后突触作用在很大程度上确定了二阶视网膜神经元的响应，则将诱发的后突触后电流将其解散到其个体量子中，并用于在不同的生理条件下（例如变化的照明水平）确定释放参数。除了了解视觉途径中的第一个突触中如何转化视觉信息外，针对感光体调节谷氨酸释放的拟议实验对于理解视网膜的病理生理学也很重要，因为增加了谷氨酸释放（例如，伴随的缺血性缺血）可能会对后伴有短伴有短与肌毒性后的神经毒性神经神经元素产生兴奋性后果。