PreBotzinger Circuit in Respiratory Rhythm Generation

越来越多的证据表明，节律产生电路的一个重要组成部分位于大脑皮层内。 延髓腹外侧的离散区域称为前B6tzinger复合体。然而，一项谅解 的preB6tzinger的贡献呼吸等待一个全面的描述有关的性质 以及组成神经元的网络相互作用。该项目的目标是提供一个合理完整的 描述前B6tzinger复合体中存在的呼吸神经元类型，包括其放电 模式，对选定传入输入激活的反应，神经递质（GABA、谷氨酸、甘氨酸） 与其他preB6tzinger神经元形成的突触连接的内容和模式。由于规模小， 前B6tzinger复合物（在成年大鼠中其约0.6 mm长和约1.5 mm直径， 包括树突），我们可以提供这种分析。将有三个具体目标。 在Aiml中，细胞内或细胞外记录将用于根据放电对神经元进行分类 迷走神经和上级喉神经传入刺激的反应。所记录的 然后将染料注入神经元。随后的免疫组织化学分析在光和 超微结构水平将确定神经递质含量（GABA，甘氨酸，谷氨酸）及其轴突 投射模式在目标2中，前B6tzinger神经元之间的突触相互作用将被识别为 互补的电生理学和解剖学方法。在电生理学方法中， 尖峰触发的平均或互相关方法将与成对的神经元记录一起使用。在 解剖实验细胞内或细胞外标记将用于在2种不同功能中染色标记细胞 组进行随后的光和其突触相互作用的超微结构分析。在目标3中，我们 使用所识别的神经元开发preB6tzinger呼吸网络的详细计算模型 属性和连通性。要解决的假设是，神经元类型和突触 preB6tzinger复合物内的相互作用足以在体内产生呼吸节律。

There is increasing evidence that an essential component of the rhythm generating circuitry is located within a discrete region of the ventrolateral medulla termed the preB6tzinger complex. Nevertheless, an understanding of the preB6tzinger contribution to breathing awaits a comprehensive description of the pertinent properties and network interactions of the constituent neurons. The goal of this project to provide a reasonably complete description of the respiratory neuron types present in the preB6tzinger complex, including their discharge patterns, response to activation of selected afferent inputs, neurotransmitter (GABA, glutamate, glycine) content and pattern of synaptic connections formed with other preB6tzinger neurons. Given the small size of the preB6tzinger complex (in the adult rat it is approximately 0.6 mm long and about 1.5 mm in diameter, including dendrites), it is within our means to provide this analysis. Three Specific Aims will be undertaken. In Aiml, intracellular or extracellular recording will be used to classify neurons with respect to discharge pattern and their response to stimulation of vagus and superior laryngeal nerve afferents. The recorded neurons will then be injected with dye. Subsequent immunohistochemical analysis at the light and ultrastructural levels will identify the neurotransmitter content (GABA, glycine, glutamate) and their axonal projection patterns. In Aim 2, synaptic interactions between preB6tzinger neurons will be identified with complementary electrophysiological and anatomical approaches. In the electrophysiological approach, either spike triggered averaging or cross-correlation approaches will be used with paired neuronal recordings. In anatomical experiments intra- or juxtacellular labeling will be used to dye-label cells in 2 different functional groups for subsequent light and ultrastructural analysis of their synaptic interactions. In Aim 3, we will develop a detailed computational model of the preB6tzinger respiratory network using the identified neuronal properties and connectivity. The hypothesis to be addressed is that the neuronal types and synaptic interactions within the preB6tzinger complex are sufficient for respiratory rhythm generation in vivo.