引用

患有神经退行性疾病的患者，如帕金森病、阿尔茨海默病和额颞叶痴呆，即使在疾病进展的早期阶段也可能出现喉运动功能障碍。喉，也叫声门，是调节呼吸气流的主要阀门。此外，声门肌肉在口面行为(如发声和吞咽)的调节中起着重要作用。例如，声门防止食物在吞咽时被吸入肺部。此外，在说话时，位于声门内的声带在呼气气流的震动下发出声音。神经退行性疾病患者的尸检研究表明，脑干呼吸网络内的神经元退行性变可能是喉运动功能障碍的原因。不足为奇的是，患者经常出现呼吸、发声和吞咽功能障碍。这些临床报告促使我的研究小组对脑干呼吸网络神经退行性变(即牛皮病)的转基因小鼠模型进行研究。弗洛里呼吸神经生物学团队的数据发现，与临床观察相似，该小鼠模型表现出喉运动功能障碍，导致呼吸和吞咽障碍。因此，下一步是研究脑干中的牛皮病是否也与超声发声受损(USV)有关。 This working hypothesis was part of my first experimental study of my PhD (chapter 2). I found that the transgenic mouse model presented USV patterns similar to the wild-type mice (control group), even during the late stage of diseases progression, when many brainstem circuits have degenerated. However, it is crucial to note that orofacial behaviours, including vocalisation, can be volitionally controlled by supra-pontine brains regions, such as the cortex and the limbic system in the forebrain, and I speculated that these control circuits for vocalisation might be able to compensate for brainstem neurodegeneration. Surprisingly, the neuroanatomical pathways that might be involved with volitional control of respiration during orofacial behaviours were poorly defined. Thus, the following experimental study (Chapter 3) examined the anatomical projections from the forebrain to the brainstem respiratory network using a retrograde tracing approach. I reported for the first time widespread descending cortical and subcortical descending projections to a subset of primary respiratory control nuclei. Functionally, this neuroanatomical framework suggests that volitional information is sent to the brainstem respiratory network to adapt breathing with orofacial behaviours, such as vocalisation. Moreover, I found a highly redundant network connectome within the brainstem respiratory network that could be implicated in the compensation of local brainstem tauopathy (Chapter 4). Collectively, data from my thesis suggest the presence of numerous pathways in the brain that may compensate for localised neurodegeneration in the respiratory network of patients with neurodegenerative diseases. In summary, my PhD thesis proposes a new neuroanatomical framework to study behavioural adaptation of breathing in healthy and neurological diseases.