Do Real Stimuli Better Evoke Backpropagation and LTP?

神经元动作电位是沿着轴突传导的电信号，以诱导突触处化学神经递质的释放。然而，动作电位也反向传播到树突，神经元的分支输入结构。虽然它的作用还没有完全理解，反向传播无疑会影响树突信号处理的重要方式。了解树突信号处理对于全面了解正常学习和记忆至关重要，其中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，某些形式的精神发育迟滞，帕金森病等。这个提议探讨了这样一种可能性，即具有现实的、不规则的时间的尖峰序列可能比通常用于实验诱导的人工规则尖峰序列更有效地产生反向传播和长时程增强（LTP），这是学习和记忆的主要模型。初始实验将测试在海马CAI锥体神经元中刺激的哪种类型的尖峰串更有效地反向传播到树突中：从体内实验中获得的真实的不规则尖峰串或相同总频率的规则尖峰串。将测试尖峰序列的各种频率分量在反向传播效率中的作用。接下来，CA 1树突的钙成像将确定真实的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，通过将阈下突触刺激序列与CA 1锥体索马体中匹配的锋电位序列配对，在Schaffer侧支-CA 1突触处产生LTP。比较真实的、不规则的和艺术的、规则的锋电位序列所诱导的LTP的量。这些实验将检验生理回退比常规刺激更有效、更容易支持LTP的假设。

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.