Do Real Stimuli Better Evoke Backpropagation and LTP?

真实刺激能更好地引发反向传播和 LTP 吗？

• 批准号: 6405643
• 负责人: VALERIE L KILMAN
• 金额: $ 1.17万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6405643
• 关键词: NMDA receptors; action potentials; cadmium; calcium channel; calcium flux; dendrites; hippocampus; laboratory rat; long term potentiation; magnesium; sodium channel; voltage /patch clamp; voltage gated channel

Neuronal action potentials are electrical signals that travel along the axon to induce release of chemical neurotransmitters at synapses. However, action potentials also backpropagate into dendrites, the branching input structures of neurons. Though its role is not fully understood, backpropagation undoubtedly affects dendritic signal processing in important ways. Understanding dendritic signal processing is critical to a full understanding of normal learning and memory, which includes changes in dendrites and dendritic inputs, and diseases involving dendritic dysfunction such as epilepsy, some forms of mental retardation, Parkinson's disease, and others. This proposal explores the possibility that spike trains with realistic, irregular timing may be more effective at generating backpropagation and long term potentiation (LTP), the primary model of learning and memory, than the artificial regular spike trains that are generally used to induce it experimentally. Initial experiments will test which type of spike train stimulated in hippocampal CAI pyramidal neurons backpropagates more efficiently into the dendrite: real, irregular spike trains taken from in vivo experiments or regular spike trains of the same overall frequency. The role of various frequency components of the spike trains in backpropagation efficiency will be tested. Next calcium imaging of the CA1 dendrites will determine if real inputs result in more calcium influx, necessary to LTP induction, than artificial inputs. Lastly, LTP will be generated at the Schaffer collateral-CA1 synapse by pairing trains of subthreshold synaptic stimuli with matched spike trains in the CA1 pyramidal soma. The amount of LTP induced by real, irregular and artficial, regular spike trains will be compared. These experiments will test the hypothesis that physiological back ro a ation is more effective and supports LTP more readil than commonly-used regular stimuli.

神经元动作电位是沿着轴突传播的电信号，诱导突触释放化学神经递质。然而，动作电位也反向传播到树突，这是神经元的分支输入结构。尽管其作用尚不完全清楚，但反向传播无疑会在重要方面影响树突信号的处理。了解树突状细胞的信号处理对于全面理解正常的学习和记忆是至关重要的，这包括树突和树突输入的变化，以及涉及树突状细胞功能障碍的疾病，如癫痫、某些形式的智力低下、帕金森氏病等。这项提议探索了这样一种可能性，即具有真实、不规则时序的棘波训练在产生反向传播和长时程增强(LTP)方面可能比通常用于实验诱导的人工规则棘波训练更有效。LTP是学习和记忆的主要模型。最初的实验将测试在海马CA1区锥体神经元中刺激的哪种类型的棘波序列向后传播到树突更有效：来自活体实验的真实的、不规则的棘波序列还是相同总频率的规则棘波序列。将测试穗序列的各种频率分量在反向传播效率中的作用。接下来，CA1树突的钙成像将确定实际输入是否比人工输入导致更多的钙内流，这是LTP诱导所必需的。最后，LTP将在Schaffer侧支-CA1突触通过将阈值下突触刺激序列与CA1锥体中匹配的棘波序列配对而产生。将比较真实的、不规则的和人工的、规则的穗列诱发的LTP的量。这些实验将检验这一假设，即生理背景性刺激比通常使用的常规刺激更有效，更支持LTP。