Location-dependent excitatory synaptic interactions in pyramidal neuron dendrites.
Location-dependent excitatory synaptic interactions in pyramidal neuron dendrites.
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DOI：
10.1371/journal.pcbi.1002599
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发表时间：
2012
影响因子：
4.3
通讯作者：
Mel BW
中科院分区：
文献类型：
--
作者：
Behabadi BF;Polsky A;Jadi M;Schiller J;Mel BW
新皮质锥体神经元在其基底树突上接受数以千计的兴奋性突触接触。其中一些作为经典的驾驶员输入，而另一些则被认为基于感觉或行为背景来调节PN反应，但在这些树突中介导经典-背景相互作用的生物物理机制仍然知之甚少。我们假设，如果两条兴奋通路将它们的突触投射偏向基底支的近端和远端，那么靠近和远离胞体的输入的非常不同的局部峰阈值和衰减因子可能为经典-语境功能不对称提供基础。支持这种可能性的是，我们在隔室模型和脑片的电生理记录中都发现，基础树突对空间分离的输入的反应确实是强烈的不对称。远端刺激降低了更近端输入的局部尖峰阈值，而对胞体的峰值反应几乎没有影响。相反，近端激发降低了阈值，但也显著增加了远端驱动反应的增益。我们的发现支持这一观点，即PN基础树突具有显著的模拟计算能力，并提示新皮质中可见的各种形式的非线性反应调制，包括单模式、跨模式和注意效应，可能部分依赖于兴奋性突触接触到PN基础树突的空间分布中的路径特有的偏向。锥体神经元是大脑皮层的主要神经元，因此位于大脑高级感觉、运动、情感、记忆和执行功能的中心。但它们是如何工作的呢？具体地说，它们如何管理导致其基本响应属性的经典“驱动”输入与非线性调节这些响应的“上下文”输入之间的交互？众所周知，三叉神经节是由散布在树突上的数千个兴奋性突触联系在一起的，但尽管有几十年的研究，支配树突树不同位置的输入如何结合起来影响细胞放电速率的“规则”仍然知之甚少。我们在这里表明，接触同一树突的两个兴奋性输入以一种不对称的非线性方式相互作用，这取决于它们的绝对和相对位置，其中产生的位置相关的突触相互作用谱构成了一种以前未知的空间模拟计算形式。除了提出了PN树突中经典-上下文相互作用的可能底物外，我们的结果还表明，只有当突触连接的详细地图-皮质连接体-深入到树突下水平时，才能完全理解皮质电路的计算功能。
Neocortical pyramidal neurons (PNs) receive thousands of excitatory synaptic contacts on their basal dendrites. Some act as classical driver inputs while others are thought to modulate PN responses based on sensory or behavioral context, but the biophysical mechanisms that mediate classical-contextual interactions in these dendrites remain poorly understood. We hypothesized that if two excitatory pathways bias their synaptic projections towards proximal vs. distal ends of the basal branches, the very different local spike thresholds and attenuation factors for inputs near and far from the soma might provide the basis for a classical-contextual functional asymmetry. Supporting this possibility, we found both in compartmental models and electrophysiological recordings in brain slices that the responses of basal dendrites to spatially separated inputs are indeed strongly asymmetric. Distal excitation lowers the local spike threshold for more proximal inputs, while having little effect on peak responses at the soma. In contrast, proximal excitation lowers the threshold, but also substantially increases the gain of distally-driven responses. Our findings support the view that PN basal dendrites possess significant analog computing capabilities, and suggest that the diverse forms of nonlinear response modulation seen in the neocortex, including uni-modal, cross-modal, and attentional effects, could depend in part on pathway-specific biases in the spatial distribution of excitatory synaptic contacts onto PN basal dendritic arbors. Pyramidal neurons (PNs) are the principal neurons of the cerebral cortex and therefore lie at the heart of the brain's higher sensory, motor, affective, memory, and executive functions. But how do they work? In particular, how do they manage interactions between the classical “driver” inputs that give rise to their basic response properties, and “contextual” inputs that nonlinearly modulate those responses? It is known that PNs are contacted by thousands of excitatory synapses scattered about their dendrites, but despite decades of research, the “rules” that govern how inputs at different locations in the dendritic tree combine to influence the cell's firing rate remain poorly understood. We show here that two excitatory inputs contacting the same dendrite interact in an asymmetric nonlinear way that depends on their absolute and relative locations, where the resulting spectrum of location-dependent synaptic interactions constitutes a previously unknown form of spatial analog computation. In addition to suggesting a possible substrate for classical-contextual interactions in PN dendrites, our results imply that the computing functions of cortical circuits can only be fully understood when the detailed map of synaptic connectivity – the cortical connectome – is known down to the subdendritic level.
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DOI：
10.1126/science.1189664
发表时间：
2010-09-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Branco T;Clark BA;Häusser M
通讯作者：
Häusser M
影响因子：
25
作者：
Archie, KA;Mel, BW
通讯作者：
Mel, BW
影响因子：
3.7
作者：
Felleman, Daniel J.;Van Essen, David C.
通讯作者：
Van Essen, David C.
影响因子：
4.2
作者：
Antic SD;Zhou WL;Moore AR;Short SM;Ikonomu KD
通讯作者：
Ikonomu KD
影响因子：
5.3
作者：
Gordon, Urit;Polsky, Alon;Schiller, Jackie
通讯作者：
Schiller, Jackie