Temperature manipulation of neuronal dynamics in a forebrain motor control nucleus.

Temperature manipulation of neuronal dynamics in a forebrain motor control nucleus.
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前脑运动控制核中神经元动力学的温度操纵。

DOI:
10.1371/journal.pcbi.1005699
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发表时间:
2017-08
影响因子:
4.3
通讯作者:
Mindlin GB
Mindlin GB
中科院分区:
生物学2区
文献类型:
--
作者:
Goldin MA;Mindlin GB

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大脑运动区域内不同类型的神经元有助于复杂运动行为的产生。一个被广泛研究的鸣禽前脑核(HVC)被认为是形成鸟类精确鸣叫时间特征的基础。除其他证据外,这是基于HVC冷却时song结构的拉伸和“断裂”。然而,人们对其神经元中发生的温度效应知之甚少。为了解决这个问题,我们从实验和计算两方面研究了HVC的动力学。我们开发了一种技术,在HVC温度操作期间同时进行电生理记录。我们记录了自发活动,发现了三种效应:穗形变宽、放电速率降低和穗间间隔分布的变化。所有这些影响都可以用HVC中所有神经元的详细电导模型来解释。离子通道时间常数的温度依赖性解释了第一种效应,而第二种效应是基于单个突触兴奋输入的最大电导的变化。最后一种现象是在向抑制性中间神经元引入更现实的突触输入后才出现的。峰间分布存在两个时间尺度。一个时间标度的行为可以通过从兴奋性神经元接收的不同输入平衡来重现,而另一个时间标度则会随着冷却而消失,假设泊松突触输入则无法找到。此外,计算模型表明,兴奋性神经元的破裂在正常脑温下自然发生,在低温下具有固有的延迟。同样的效应也发生在单个突触上,这可能解释了歌曲拉伸的原因。这些发现揭示了神经元动力学的温度依赖性,并为研究神经元连接提供了一个全面的框架。这项基于内在神经元特征的研究,可能有助于理解突发性行为变化。最近,对引起鸟类复杂鸣叫行为的神经元机制的研究引起了激烈的争论。许多模型已经被测试,新的工具已经被开发出来,试图理解一个关键的脑核在歌唱途径中的作用:HVC。人们认为,它对产生歌曲的精确时间负有很大的责任,这一点已经通过控制温度进行了测试。结果表明,冷却可以拉伸,但它也可以重组或“打断”歌曲的音节。然而,单个神经元的机制尚未被描述。为了更好地理解这一点,我们冷却了金丝雀的HVC,并从电生理上测量了自发活动。我们发现了三种效应:尖峰形状变宽、尖峰速率降低和尖峰间隔(ISI)分布的变化。为了解释它们,我们建立了一个计算模型,详细描述了离子通道电导和温度依赖性。我们可以用单个神经元模型来解释第一种效应。第二,可以解释为增加单个突触。最后,我们通过多个随机输入显示了其中一个时间尺度的类似ISI修改。此外,我们发现兴奋性神经元在正常大脑温度下表现出自然的破裂行为,突触延迟是解释低温下歌曲拉伸的主要候选因素。
Different neuronal types within brain motor areas contribute to the generation of complex motor behaviors. A widely studied songbird forebrain nucleus (HVC) has been recognized as fundamental in shaping the precise timing characteristics of birdsong. This is based, among other evidence, on the stretching and the “breaking” of song structure when HVC is cooled. However, little is known about the temperature effects that take place in its neurons. To address this, we investigated the dynamics of HVC both experimentally and computationally. We developed a technique where simultaneous electrophysiological recordings were performed during temperature manipulation of HVC. We recorded spontaneous activity and found three effects: widening of the spike shape, decrease of the firing rate and change in the interspike interval distribution. All these effects could be explained with a detailed conductance based model of all the neurons present in HVC. Temperature dependence of the ionic channel time constants explained the first effect, while the second was based in the changes of the maximal conductance using single synaptic excitatory inputs. The last phenomenon, only emerged after introducing a more realistic synaptic input to the inhibitory interneurons. Two timescales were present in the interspike distributions. The behavior of one timescale was reproduced with different input balances received form the excitatory neurons, whereas the other, which disappears with cooling, could not be found assuming poissonian synaptic inputs. Furthermore, the computational model shows that the bursting of the excitatory neurons arises naturally at normal brain temperature and that they have an intrinsic delay at low temperatures. The same effect occurs at single synapses, which may explain song stretching. These findings shed light on the temperature dependence of neuronal dynamics and present a comprehensive framework to study neuronal connectivity. This study, which is based on intrinsic neuronal characteristics, may help to understand emergent behavioral changes. The study of the neuronal mechanisms that give rise to the complex behavior of singing in birds has been hotly debated lately. Many models have been tested and novel tools have been developed to try to understand the role of a key brain nucleus in the song pathway: HVC. It is believed that it is highly responsible for generating the precise timing of songs, and this has been tested by manipulating it with temperature. Results showed that cooling can stretch, but that it can also restructure or “break” the song syllables. However, single neuronal mechanisms are not yet described. To better understand this, we cooled HVC in canaries and measured spontaneous activity electrophysiologically. We found three effects: spike shape widening, spike rate reduction and changes in inter-spike-interval (ISI) distributions. To explain them, we built a computational model with a detailed description of ion channel conductances and temperature dependency. We could explain the first effect with a single neuron model. The second, could be explained adding single synapses. Finally, we showed similar ISI modifications of one of the timescales present by means of multiple stochastic inputs. In addition, we found that excitatory neurons show natural bursting behavior at normal brain temperatures and that synaptic delays are the main candidates to explain song stretching at low temperatures.
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