GABA is a modulator, rather than a classical transmitter, in the medial nucleus of the trapezoid body-lateral superior olive sound localization circuit
GABA is a modulator, rather than a classical transmitter, in the medial nucleus of the trapezoid body-lateral superior olive sound localization circuit
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DOI：
10.1113/jp277566
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发表时间：
2019-04-15
影响因子：
5.5
通讯作者：
Friauf, Eckhard
中科院分区：
文献类型：
--
作者：
Fischer, Alexander U.;Mueller, Nicolas I. C.;Friauf, Eckhard
GABA和甘氨酸介导快速抑制性神经传递，并在几种突触类型中共同释放。在这里，我们评估了GABA和甘氨酸在梯形体内侧核（MNTB）和外侧上橄榄核（LSO）之间的突触传递中的作用，这两个核参与声音定位。在对GABA(A)受体（GABA（A)Rs）和/或甘氨酸受体进行药物阻断的急性小鼠脑干切片(P) 4和11天）的全细胞膜片钳实验显示，在LSO主神经元上没有GABA能突触成分。在诱发的抑制性突触后电流和微型事件中缺乏gaba能成分。共免疫荧光实验显示，突触前GABA能标记物GAD65/67与GABA(a)Rs的突触后标记物gephyrin没有共分布，证实了GABA在小鼠LSO中没有突触作用的结论。成像实验显示，激活突触前GABA(B)Rs后，MNTB轴突末端的Ca2+内流减少。GABA(B)R的激活降低了P4和P11的突触强度。GABA似乎作用于突触外GABA(A)Rs，这是通过应用一种亚基特异性GABA(A)R激动剂4,5,6,7-四氢异恶唑[5,4-c]吡啶-3-醇证实的。RNA测序显示，LSO中-亚基的mRNA水平较高。此外，GABA转运体GAT-1和GAT-3似乎控制细胞外GABA。最后，我们展示了GABA对LSO神经元兴奋性的年龄依赖性影响。虽然强直性GABA增加P4的兴奋性，导致spike促进，但它通过突触外GABA(A)Rs的分流抑制降低P11的兴奋性。综上所述，我们证明了GABA在小鼠LSO中的调节作用，而不是作为经典的突触递质的功能。
GABA and glycine mediate fast inhibitory neurotransmission and are coreleased at several synapse types. Here we assessed the contribution of GABA and glycine in synaptic transmission between the medial nucleus of the trapezoid body (MNTB) and the lateral superior olive (LSO), two nuclei involved in sound localization. Whole-cell patch-clamp experiments in acute mouse brainstem slices at postnatal days (P) 4 and 11 during pharmacological blockade of GABA(A) receptors (GABA(A)Rs) and/or glycine receptors demonstrated no GABAergic synaptic component on LSO principal neurons. A GABAergic component was absent in evoked inhibitory postsynaptic currents and miniature events. Coimmunofluorescence experiments revealed no codistribution of the presynaptic GABAergic marker GAD65/67 with gephyrin, a postsynaptic marker for GABA(A)Rs, corroborating the conclusion that GABA does not act synaptically in the mouse LSO. Imaging experiments revealed reduced Ca2+ influx into MNTB axon terminals following activation of presynaptic GABA(B)Rs. GABA(B)R activation reduced the synaptic strength at P4 and P11. GABA appears to act on extrasynaptic GABA(A)Rs as demonstrated by application of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol, a -subunit-specific GABA(A)R agonist. RNA sequencing showed high mRNA levels for the -subunit in the LSO. Moreover, GABA transporters GAT-1 and GAT-3 appear to control extracellular GABA. Finally, we show an age-dependent effect of GABA on the excitability of LSO neurons. Whereas tonic GABA increased the excitability at P4, leading to spike facilitation, it decreased the excitability at P11 via shunting inhibition through extrasynaptic GABA(A)Rs. Taken together, we demonstrate a modulatory role of GABA in the murine LSO, rather than a function as a classical synaptic transmitter.