SYNAPTIC INHIBITORY PROCESSES IN BREATHING CONTROL

描述(改编自申请者的摘要)：呼吸是一种复杂的 一种重复的行为，其中中央产生的节奏被翻译成 精确的运动模式。快速突触抑制，由递质等介导 与GABA和甘氨酸一样，产生于网络生成的固有神经元 呼吸节律，通常被认为在世代中很重要 并在体内控制成年哺乳动物的呼吸节律和模式。 最近发现的第二种快速GABA能抑制，称为 外源性抑制，外在出现于相呼吸网络的外部 神经元和基础的比例增益控制的活动相 呼吸神经元活跃。虽然这种形式的抑制很可能会有 生理角色的多样性及其对呼吸运动的强大影响 结果表明，它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 在运动或发声等复杂行为中。重要的是 这种形式的抑制来自于它调节神经元整体 活跃度级别，同时维护 每一呼吸时相呼吸神经元放电的详细模式。 这种抑制在静息条件下是音调活跃的，减少了 球脊髓运动前神经元自发活动水平约为20-30 在没有这种投入的情况下，他们的排泄率的百分比。因此， 一种生理状态，可导致大脑中的 这种持续抑制的程度可以引起呼吸系统的显著变化 马达输出。作为阐明其生理功能的关键的第一步 角色，并行的解剖学和电生理方法将识别 有助于获得控制的紧张性抑制的外部来源， 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 目标是确定：1)GABA能突触前来源是什么 呼吸神经元的抑制性输入以及GABA能终末和 受体分布在它们的表面，2)获得控制的范围有多广 参与建立呼吸神经元放电(即，什么 呼吸神经元的类别表现出GABA介导的增益控制)，以及3) 增益控制是由突触前和/或突触后抑制介导的吗？如果是 突触后，它对固有细胞特性有什么影响？鉴定 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.