Do Real Stimuli Better Evoke Backpropagation and LTP?

神经元动作电位是沿轴突传播的电信号，可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，神经元的分支输入结构。虽然反向传播的作用还不完全清楚，但它无疑在重要方面影响了树突信号的处理。理解树突信号处理对于全面理解正常的学习和记忆至关重要，这包括树突和树突输入的变化，以及涉及树突功能障碍的疾病，如癫痫、某些形式的智力迟钝、帕金森氏病等。这一提议探讨了具有现实的、不规则时序的脉冲序列在产生反向传播和长期增强（LTP）（学习和记忆的主要模型）方面比通常用于诱导学习和记忆的人工规则脉冲序列更有效的可能性。最初的实验将测试哪一种刺激海马CAI锥体神经元的尖峰序列更有效地反向传播到树突：从体内实验中获得的真实的，不规则的尖峰序列还是相同总频率的规则尖峰序列。将测试尖峰串的各种频率分量在反向传播效率中的作用。下一步，CA1树突的钙成像将确定真实输入是否比人工输入导致更多的钙流入，这是LTP诱导所必需的。最后，LTP将在Schaffer侧侧-CA1突触通过阈下突触刺激序列与CA1锥体中匹配的spike序列配对而产生。将比较真实的、不规则的和人工的、规则的尖峰列车所引起的LTP量。这些实验将验证一个假设，即生理回调比常用的常规刺激更有效，更容易支持LTP。

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.