Department Biology II, Ludwig-Maximilians-Universität München, München, Germany, 82152.
Graduate School of Systemic Neurosciences, Ludwig-Maximilians-Universität München, München, Germany, 82152.
J Neurosci. 2021 Jan 13;41(2):269-283. doi: 10.1523/JNEUROSCI.1055-20.2020. Epub 2020 Nov 18.
Neurons in the medial superior olive (MSO) detect 10 µs differences in the arrival times of a sound at the two ears. Such acuity requires exquisitely precise integration of binaural synaptic inputs. There is substantial understanding of how neuronal phase locking of afferent MSO structures, and MSO membrane biophysics subserve such high precision. However, we still lack insight into how the entirety of excitatory inputs is integrated along the MSO dendrite under sound stimulation. To understand how the dendrite integrates excitatory inputs as a whole, we combined anatomic quantifications of the afferent innervation in gerbils of both sexes with computational modeling of a single cell. We present anatomic data from confocal and transmission electron microscopy showing that single afferent fibers follow a single dendrite mostly up to the soma and contact it at multiple (median 4) synaptic sites, each containing multiple independent active zones (the overall density of active zones is estimated as 1.375 per μm). Thus, any presynaptic action potential may elicit temporally highly coordinated synaptic vesicle release at tens of active zones, thereby achieving secure transmission. Computer simulations suggest that such an anatomic arrangement boosts the amplitude and sharpens the time course of excitatory postsynaptic potentials by reducing current sinks and more efficiently recruiting subthreshold potassium channels. Both effects improve binaural coincidence detection compared with single large synapses at the soma. Our anatomic data further allow for estimation of a lower bound of 7 and an upper bound of 70 excitatory fibers per dendrite. Passive dendritic propagation attenuates the amplitude of postsynaptic potentials and widens their temporal spread. Neurons in the medial superior olive, with their large bilateral dendrites, however, can detect coincidence of binaural auditory inputs with submillisecond precision, a computation that is in stark contrast to passive dendritic processing. Here, we show that dendrites can counteract amplitude attenuation and even decrease the temporal spread of postsynaptic potentials, if active subthreshold potassium conductances are triggered in temporal coordination along the whole dendrite. Our anatomic finding that axons run in parallel to the dendrites and make multiple synaptic contacts support such coordination since incoming action potentials would depolarize the dendrite at multiple sites within a brief time interval.
中脑上橄榄核（MSO）中的神经元可以检测到声音到达双耳的时间差为 10 微秒。如此高的灵敏度需要对双耳传入的突触输入进行极其精确的整合。人们已经对传入 MSO 结构的神经元相位锁定以及 MSO 膜生物物理学如何支持这种高精度有了相当的了解。然而，我们仍然缺乏对在声音刺激下整个兴奋性输入是如何沿着 MSO 树突整合的深入了解。为了了解树突如何整体整合兴奋性输入，我们结合了两性沙土鼠的传入神经支配的解剖学定量分析和单个细胞的计算建模。我们提供了来自共聚焦和透射电子显微镜的解剖学数据，这些数据表明，单个传入纤维主要沿着单个树突延伸到胞体，并在多个（中位数 4 个）突触位点与之接触，每个位点包含多个独立的活性区（活性区的总体密度估计为每 μm 有 1.375 个）。因此，任何一个突触前动作电位都可能在数十个活性区引发时间高度协调的突触小泡释放，从而实现可靠的传递。计算机模拟表明，这种解剖结构通过减少电流汇并更有效地招募亚阈值钾通道，从而提高兴奋性突触后电位的幅度并使时间进程变陡。与胞体上的单个大突触相比，这两种效应都能提高双耳 coincidence 检测的性能。我们的解剖学数据还允许估计每个树突有 7 到 70 个兴奋性纤维。被动树突传播会衰减突触后电位的幅度并扩大其时间扩散。然而，具有大的双侧树突的中脑上橄榄核神经元可以以亚毫秒级的精度检测双耳听觉输入的 coincidence，这种计算与被动树突处理形成鲜明对比。在这里，我们表明，如果沿整个树突在时间上协调地触发活性亚阈值钾电导，则树突可以抵消幅度衰减，甚至可以减少突触后电位的时间扩散。我们的解剖学发现，轴突与树突平行运行并形成多个突触接触，支持这种协调，因为传入的动作电位会在很短的时间间隔内在多个位点使树突去极化。
