Irregular Breathing in Mice following Genetic Ablation of V2a Neurons

Irregular Breathing in Mice following Genetic Ablation of V2a Neurons
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DOI:
10.1523/jneurosci.0445-12.2012
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发表时间:
2012-06-06
影响因子:
5.3
通讯作者:
Sharma, Kamal
Sharma, Kamal
中科院分区:
医学1区
文献类型:
--
作者:
Crone, Steven A.;Viemari, Jean-Charles;Sharma, Kamal

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被称为中枢模式发生器(cpg)的神经网络产生重复的运动行为,如运动和呼吸。谷氨酸能神经元是与重复性运动行为相关的运动活动模式的产生和抑制神经元所必需的。在小鼠中,谷氨酸能V2a神经元协调脊髓中左右腿CPGs的活动,使小鼠产生交替的步态。在这里,我们研究了V2a神经元在呼吸神经控制中的作用,呼吸是一种重要的重复性运动行为。我们发现,在V2a神经元消融后,新生小鼠的呼吸频率较低。脑干-脊髓呼吸活动记录和呼吸切片显示,缺乏V2a神经元的小鼠中枢呼吸节律产生不足。呼吸切片制备过程中V2a神经元的缺失可以通过大量使用已知的加速呼吸节奏的神经化学物质来弥补。在切片制备中,V2a神经元表现出强直性放电模式。内侧网状结构V2a神经元与pre-Botzinger复合体神经元之间存在直接连接,表明V2a神经元在新生小鼠呼吸CPG功能中起直接作用。因此,胚胎V2a谱系的神经元似乎已经被招募到控制呼吸和运动的神经网络中,这是两种突出的cpg驱动的重复运动行为。
Neural networks called central pattern generators (CPGs) generate repetitive motor behaviors such as locomotion and breathing. Glutamatergic neurons are required for the generation and inhibitory neurons for the patterning of the motor activity associated with repetitive motor behaviors. In the mouse, glutamatergic V2a neurons coordinate the activity of left and right leg CPGs in the spinal cord enabling mice to generate an alternating gait. Here, we investigate the role of V2a neurons in the neural control of breathing, an essential repetitive motor behavior. We find that, following the ablation of V2a neurons, newborn mice breathe at a lower frequency. Recordings of respiratory activity in brainstem-spinal cord and respiratory slice preparations demonstrate that mice lacking V2a neurons are deficient in central respiratory rhythm generation. The absence of V2a neurons in the respiratory slice preparation can be compensated for by bath application of neurochemicals known to accelerate the breathing rhythm. In this slice preparation, V2a neurons exhibit a tonic firing pattern. The existence of direct connections between V2a neurons in the medial reticular formation and neurons of the pre-Botzinger complex indicates that V2a neurons play a direct role in the function of the respiratory CPG in newborn mice. Thus, neurons of the embryonic V2a lineage appear to have been recruited to neural networks that control breathing and locomotion, two prominent CPG-driven, repetitive motor behaviors.