SYNAPTIC INHIBITORY PROCESSES IN BREATHING CONTROL

描述（改编自申请人的摘要）：呼吸是一种复杂的 重复的行为，在这种行为中，中央产生的节奏被转化为 精确的运动模式快速突触抑制，由诸如 如GABA和甘氨酸，来自神经元内在的网络产生 呼吸节律，一般认为是重要的一代 以及在成年哺乳动物体内控制这种呼吸节律和模式。 最近发现的第二种类型的快速GABA能抑制，称为 外源性抑制，产生于相位呼吸网络的外部 神经元和基础的比例增益控制的活动相 活跃的呼吸神经元虽然这种形式的抑制可能会有一个 多种生理作用，对呼吸运动的强大影响 输出表明其可能有助于呼吸保护反射（例如， 咳嗽，打喷嚏）或有助于呼吸与其他系统的整合 在复杂的行为如运动或发声过程中。的重要性 这种形式的抑制来自于它调节神经元整体功能的能力。 活动水平，同时保持 每个呼吸时相内呼吸神经元放电的详细模式。 这种抑制作用在静息条件下具有张力活性， 将球脊髓前运动神经元中自发活动水平提高到约20 - 30 在没有这种输入的情况下，其放电率的百分比。因此，在本发明中， 生理条件，导致增加或减少， 这种持续抑制的程度可以引起呼吸系统的显著变化， 电机输出作为阐明其生理机制的关键第一步 作用，并行解剖和电生理方法将确定 有助于增益控制的紧张性抑制的外在来源， 这些神经元的传出突触接触和电生理 这种抑制性输入对突触后神经元的影响。三大 目的是确定：1）GABA能的突触前来源是什么 抑制输入呼吸神经元和如何GABA能终端和 受体分布在它们的表面，2）获得控制的范围有多广 参与呼吸神经元放电的建立（即， 类别的呼吸神经元表现出GABA介导的增益控制），以及3） 是由突触前和/或突触后抑制介导的增益控制，如果是， 突触后，它对细胞的内在特性有什么影响？识别 控制呼吸节律和模式的神经通路有 充分了解各种临床疾病的先决条件，如 睡眠呼吸暂停和中枢性低通气综合征。

DESCRIPTION (Adapted from the applicant's abstract): Breathing is a complex repetitive behavior in which a centrally generated rhythm is translated into a precise motor pattern. Fast synaptic inhibition, mediated by transmitters such as GABA and glycine, arises from neurons intrinsic to the network generating respiratory rhythm and is generally believed to be important in the generation and control of this respiratory rhythm and pattern in the adult mammal in vivo. A recently discovered second type of fast GABAergic inhibition, termed extrinsic inhibition, arises externally to the network of phasic respiratory neurons and underlies a proportional gain control of the activity of phasically active respiratory neurons. While this form of inhibition is likely to have a variety of physiological roles, its powerful influence on respiratory motor output suggests it may contribute to respiratory protective reflexes (eg, cough, sneeze) or contribute to the integration of breathing with other systems during complex behaviors such as locomotion or vocalization. The importance of this form of inhibition derives from its ability to regulate a neuron's overall level of activity while maintaining the information content inherent in the detailed pattern of respiratory neuron discharge within each respiratory phase. This inhibition is tonically active under resting conditions, reducing the spontaneous level of activity in bulbospinal premotor neurons to about 20-30 percent of their discharge rate in the absence of this input. Thus, physiological conditions that result in either an increase or decrease in the magnitude of this ongoing inhibition can elicit marked changes in respiratory motor output. As a critical initial step toward elucidating its physiological role, parallel anatomical and electrophysiological approaches will identify extrinsic sources of tonic inhibition contributing to gain control, the efferent synaptic contacts of these neurons and the electrophysiological consequences of this inhibitory input to postsynaptic neurons. The three major goals are to determine: 1) what are the presynaptic sources of GABAergic inhibitory input to respiratory neurons and how do GABAergic terminals and receptors distribute on their surface, 2) how broadly does gain control participate in the establishment of respiratory neuron discharge (ie, what categories of respiratory neurons exhibit GABA-mediated gain control), and 3) is gain control mediated by pre- and/or post-synaptic inhibition and, if it is postsynaptic, what are its effects on intrinsic cell properties? Identification of the neuronal pathways controlling respiratory rhythm and pattern are prerequisite for full understanding of a variety of clinical disorders such as sleep apnea and central hypoventilation syndrome.