Department of Physiology & Pharmacology, Oregon Health & Science University, Portland OR, USA.
J Physiol. 2012 Nov 15;590(22):5677-89. doi: 10.1113/jphysiol.2012.241976. Epub 2012 Sep 3.
Visceral primary afferents enter the CNS at the caudal solitary tract nucleus (NTS), and activate central pathways key to autonomic and homeostatic regulation. Excitatory transmission from primary solitary tract (ST)-afferents consists of multiple contacts originating from single axons that offer a remarkably high probability of glutamate release and high safety factor for ST afferent excitation. ST afferent activation sometimes triggers polysynaptic GABAergic circuits, which feedback onto second-order NTS neurons. Although inhibitory transmission is observed at second-order neurons, much less is known about the organization and mechanisms regulating GABA transmission. Here, we used a focal pipette to deliver minimal stimulus shocks near second-order NTS neurons in rat brainstem slices and directly activated single GABAergic axons. Most minimal focal shocks activated low jitter EPSCs from single axons with characteristics resembling ST afferents. Much less commonly (9% of sites), minimal focal shocks activated monosynaptic IPSCs at fixed latency (low jitter) that often failed (30%) and had no frequency-dependent facilitation or depression. These GABA release characteristics contrasted markedly to the unfailing, large amplitudes for glutamate released during ST-EPCSs recorded from the same neurons. Surprisingly, unitary GABAergic IPSCs were only weakly calcium dependent. In some neurons, strong focal shocks evoked compound IPSCs indicating convergent summation of multiple inhibitory axons. Our studies demonstrate that second-order NTS neurons receive GABAergic transmission from a diffuse network of inhibitory axons that rely on an intrinsically less reliable and substantially weaker release apparatus than ST excitation. Effective inhibition depends on co-activation of convergent inputs to blunt excitatory drive.
内脏初级传入纤维在尾侧孤束核(NTS)进入中枢神经系统,并激活对自主和体内平衡调节至关重要的中枢途径。初级孤束(ST)传入的兴奋性传递由源自单个轴突的多个接触组成,这些接触提供了极高的谷氨酸释放概率和 ST 传入兴奋的高安全系数。ST 传入的激活有时会触发多突触 GABA 能回路,这些回路反馈到第二级 NTS 神经元。尽管在第二级神经元中观察到抑制性传递,但关于 GABA 传递的组织和机制知之甚少。在这里,我们使用聚焦微电极在大鼠脑干切片中的第二级 NTS 神经元附近传递最小刺激冲击,并直接激活单个 GABA 能轴突。大多数最小的焦点冲击会从单个轴突激活具有类似于 ST 传入特征的低抖动 EPSC。很少见(9%的部位),最小的焦点冲击会以固定潜伏期(低抖动)激活单突触 IPSC,这些 IPSC 经常失败(30%),并且没有频率依赖性易化或压抑。这些 GABA 释放特征与从同一神经元记录的 ST-EPCs 中释放的谷氨酸具有的可靠、大振幅形成鲜明对比。令人惊讶的是,单位 IPSC 仅具有较弱的钙依赖性。在一些神经元中,强烈的焦点冲击会引发复合 IPSC,表明多个抑制性轴突的会聚总和。我们的研究表明,第二级 NTS 神经元接收来自抑制性轴突的弥散网络的 GABA 传递,该网络依赖于内在可靠性较低且释放装置明显较弱的装置,而不是 ST 兴奋。有效的抑制取决于会聚输入的共同激活,以削弱兴奋驱动。