Modelling Feedback Excitation, Pacemaker Properties and Sensory Switching of Electrically Coupled Brainstem Neurons Controlling Rhythmic Activity.
Modelling Feedback Excitation, Pacemaker Properties and Sensory Switching of Electrically Coupled Brainstem Neurons Controlling Rhythmic Activity.
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DOI：
10.1371/journal.pcbi.1004702
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发表时间：
2016-01
影响因子：
4.3
通讯作者：
Roberts A
中科院分区：
文献类型：
--
作者：
Hull MJ;Soffe SR;Willshaw DJ;Roberts A
是什么细胞和网络特性使得神经元节律的产生或点燃可以通过短暂的突触输入启动和停止？我们研究了驱动幼蛙蝌蚪游泳运动的脑干神经元电耦合群体的节律活动，以及活动如何通过短暂的感官刺激而开关。我们建立了蝌蚪后脑和脊髓一侧 30 个电耦合条件起搏器神经元的计算模型。根据对神经元特性、群体大小、突触强度和连接的实验估计，我们证明：神经元之间持久的、相互的谷氨酸能兴奋使网络在短暂的突触兴奋后能以游泳频率维持有节律的起搏器发射；如果没有电耦合，活动会持续，但节律会中断；NMDA 电压依赖性使产生持续节律的突触反馈强度范围加倍。通过短暂的突触兴奋和抑制，该网络可在短潜伏期内开启或关闭。我们证明，通过谷氨酸能兴奋反馈耦合的一般霍奇金-赫胥黎型神经元群可以通过突触开关产生持续的异步发射。我们的结论是，具有 NMDAR 介导的反馈兴奋的神经元网络可以在短暂的突触兴奋后产生自我维持的活动。活动频率受神经元膜通道动力学的限制，并可被短暂的抑制性输入所阻止。如果神经元是电耦合的，网络活动在较低频率下也会有节律。我们的主要发现是，神经元群中的兴奋性突触反馈可以在没有突触抑制的情况下产生可切换的、稳定的、持续的发射。
咀嚼、抓挠和行走等有节奏的动作需要开关。一旦开始，大脑和脊髓中驱动肌肉的神经元网络就会产生节律。我们利用幼蛙蝌蚪游泳网络的计算机模型，来探究具有反馈兴奋的电耦合脑干神经元如何产生节律活动，以及如何通过感觉刺激来开关节律活动。幼小的蝌蚪在触碰物体时会游动几秒钟，而在接触到固体物体时会停止。游泳节律可由脑干两侧各约 30 个网状脊髓神经元组成的最小群体产生。提供兴奋性启动信号和抑制性停止信号的感觉通路是已知的。在我们的模型网络中，根据生物学证据，短暂的突触兴奋可以激活稳定的游泳节律，这种节律由网状脊髓神经元之间的相互兴奋维持；游泳可以通过短暂的抑制停止。更一般的神经元相互兴奋模型网络可以产生可切换的、持续的非节律性发射。我们的结论是，提供正反馈的相互兴奋可使小神经元群产生稳定的节律性或非节律性发射，并可通过感觉输入快速开启或关闭。
What cellular and network properties allow reliable neuronal rhythm generation or firing that can be started and stopped by brief synaptic inputs? We investigate rhythmic activity in an electrically-coupled population of brainstem neurons driving swimming locomotion in young frog tadpoles, and how activity is switched on and off by brief sensory stimulation. We build a computational model of 30 electrically-coupled conditional pacemaker neurons on one side of the tadpole hindbrain and spinal cord. Based on experimental estimates for neuron properties, population sizes, synapse strengths and connections, we show that: long-lasting, mutual, glutamatergic excitation between the neurons allows the network to sustain rhythmic pacemaker firing at swimming frequencies following brief synaptic excitation; activity persists but rhythm breaks down without electrical coupling; NMDA voltage-dependency doubles the range of synaptic feedback strengths generating sustained rhythm. The network can be switched on and off at short latency by brief synaptic excitation and inhibition. We demonstrate that a population of generic Hodgkin-Huxley type neurons coupled by glutamatergic excitatory feedback can generate sustained asynchronous firing switched on and off synaptically. We conclude that networks of neurons with NMDAR mediated feedback excitation can generate self-sustained activity following brief synaptic excitation. The frequency of activity is limited by the kinetics of the neuron membrane channels and can be stopped by brief inhibitory input. Network activity can be rhythmic at lower frequencies if the neurons are electrically coupled. Our key finding is that excitatory synaptic feedback within a population of neurons can produce switchable, stable, sustained firing without synaptic inhibition. Rhythmic actions like chewing, scratching and walking need to be switched on and off. Once started, rhythms are generated by networks of neurons in the brain and spinal cord which drive muscles. We use computer models of the swimming network in young frog tadpoles to ask how electrically-coupled brainstem neurons with feedback excitation generate rhythmic activity and how this can be switched on and off by sensory stimuli. Young tadpoles swim for several seconds when touched and stop when they contact a solid object. Swimming rhythms can be generated by minimal populations of ~30 reticulospinal neurons on each side of the brainstem. The sensory pathways providing excitatory start and inhibitory stop signals are known. In our model network, based closely on biological evidence, brief synaptic excitation can activate a stable swimming rhythm sustained by mutual excitation among the reticulospinal neurons; swimming can be stopped by brief inhibition. Model networks of more generic neurons with mutual excitation can produce switchable, sustained non-rhythmic firing. We conclude that mutual excitation, providing positive feedback, can enable stable rhythmic or non-rhythmic firing in small neuron populations that can be rapidly turned on and off by sensory inputs.