Cranial afferent glutamate heterosynaptically modulates GABA release onto second-order neurons via distinctly segregated metabotropic glutamate receptors
Cranial afferent glutamate heterosynaptically modulates GABA release onto second-order neurons via distinctly segregated metabotropic glutamate receptors
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DOI：
10.1523/jneurosci.1991-04.2004
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发表时间：
2004-10-20
影响因子：
5.3
通讯作者：
Andresen, MC
中科院分区：
文献类型：
--
作者：
Jin, YH;Bailey, TW;Andresen, MC
兴奋和抑制之间的平衡决定了中枢整合。谷氨酸能和γ-氨基丁酸能神经传递主导这一过程。颅侧初级传入神经进入脑干，将谷氨酸（Glu）释放到孤束核尾侧（NTS）内的二级神经元上，以启动自主反射。这些反射的最简单的路径包含两个中枢神经元，但显示出强大的频率依赖性行为。在NTS内，存在多种代谢型Glu受体（mGluRs），但其作用知之甚少。使用突触歧视的二阶NTS神经元在脑干切片和机械分离的NTS神经元与完整的扣，我们表明，谷氨酸差异控制GABA的释放通过不同的突触前mGluRs。在切片中记录的二级NTS神经元中，以低至每秒10次电击的频率激活初级传入神经释放足够的Glu以改变自发IPSC（sIPSC）的速率。在这两种方法中，I组mGluRs增加了一些神经元中的GABA释放，但是，在不同的神经元上，II组和III组mGluRs降低了sIPSC速率。mGluR的作用非常迅速，在100毫秒内开始发作和逆转。在所有情况下，mGluR的行动完全是突触前，和mGluRs没有改变在二阶神经元中的切片或孤立的神经元突触后特性。用辣椒素和ATP进行的试验表明，有髓和无髓传入通路都涉及mGluR-GABA机制。传入Glu溢出在NTS中提供具有GABA能抑制的异突触串扰。这个过程可能会严重塑造的动态字符和使用依赖性颅传入传输的第一阶段的自主反射。
The balance between excitation and inhibition dictates central integration. Glutamatergic and GABAergic neurotransmission dominate this process. Cranial primary afferents enter the brainstem to release glutamate (Glu) onto second-order neurons within the caudal nucleus tractus solitarius (NTS) to initiate autonomic reflexes. The simplest pathways for these reflexes contain as few as two central neurons, but display robust frequency-dependent behavior. Within NTS, multiple metabotropic Glu receptors (mGluRs) are present, but their roles are poorly understood. Using synaptically discriminated second-order NTS neurons in brainstem slices and mechanically dissociated NTS neurons with intact boutons, we show that Glu differentially controls GABA release via distinct presynaptic mGluRs. In second-order NTS neurons recorded in slices, activation of primary afferents at frequencies as low as 10 shocks per second released sufficient Glu to alter rates of spontaneous IPSCs (sIPSCs). In both approaches, group I mGluRs increased GABA release in some neurons, but, on different neurons, group II and group III mGluRs decreased the sIPSC rate. mGluR actions were remarkably rapid, with onset and reversal beginning within 100 msec. In all cases, mGluR actions were exclusively presynaptic, and mGluRs did not alter postsynaptic properties in second-order neurons in either slices or isolated neurons. Tests with capsaicin and alphabeta-methylene ATP suggest that myelinated and unmyelinated afferent pathways engage both mGluR-GABA mechanisms. Afferent Glu spillover provides heterosynaptic cross talk with GABAergic inhibition in NTS. This process may critically shape the dynamic character and use dependence for cranial afferent transmission at the first stage of autonomic reflexes.