α2A-Adrenergic Receptors Filter Parabrachial Inputs to the Bed Nucleus of the Stria Terminalis
α2A-Adrenergic Receptors Filter Parabrachial Inputs to the Bed Nucleus of the Stria Terminalis
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DOI：
10.1523/jneurosci.0822-14.2014
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发表时间：
2014-07-09
影响因子：
5.3
通讯作者：
Winder, Danny G.
中科院分区：
文献类型：
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作者：
Flavin, Stephanie A.;Matthews, Robert T.;Winder, Danny G.
终纹床核（BNST）内的α（2）-肾上腺素能受体（AR）减少啮齿动物模型中的应激-奖赏相互作用。除了作为自身受体的作用外，BNST α（2A）-AR还抑制多巴胺能传递。BNST的一个突出的神经元能输入来源于臂旁核（PBN），由含有降钙素基因相关肽（CGRP）和vGluT 2的不对称轴体突触组成。在这里，我们提供的免疫电镜数据显示，许多不对称的轴体突触在BNST含有α（2A）-AR。此外，我们研究了光学诱发的谷氨酸释放离体BNST与病毒传递的通道视紫红质2（ChR 2）的PBN表达的小鼠。在这些动物的BNST中，ChR 2与CGRP部分共定位，并且激活在背侧前外侧BNST神经元中产生EPSC，引起两种细胞类型特异性结果：（1）前馈抑制或（2）引起放电的EPSP。我们发现，α（2A）-AR激动剂胍法辛选择性地抑制这种PBN输入BNST，优先减少兴奋性反应，在离体小鼠脑切片。为了开始评估α（2A）-AR控制PBN输入对BNST兴奋性传递的总体影响，我们使用了Thy 1-COP 4小鼠系，其突触后ChR 2表达很少，也没有ChR 2与CGRP在BNST中共定位。在这些小鼠的切片中，我们发现胍法辛增强而不是抑制BNST中光遗传学启动的兴奋性驱动。因此，我们的研究揭示了不同的行动PBN传入内的BNST，并表明，α（2A）-AR激动剂可能会过滤兴奋性传输的BNST通过抑制PBN输入的一个组成部分，同时增强其他输入的行动。
alpha(2)-adrenergic receptors (AR) within the bed nucleus of the stria terminalis (BNST) reduce stress-reward interactions in rodent models. In addition to their roles as autoreceptors, BNST alpha(2A)-ARs suppress glutamatergic transmission. One prominent glutamatergic input to the BNST originates from the parabrachial nucleus (PBN) and consists of asymmetric axosomatic synapses containing calcitonin gene-related peptide (CGRP) and vGluT2. Here we provide immunoelectron microscopic data showing that many asymmetric axosomatic synapses in the BNST contain alpha(2A)-ARs. Further, we examined optically evoked glutamate release ex vivo in BNST from mice with virally delivered channelrhodopsin2 (ChR2) expression in PBN. In BNST from these animals, ChR2 partially colocalized with CGRP, and activation generated EPSCs in dorsal anterolateral BNST neurons that elicited two cell-type-specific outcomes: (1) feedforward inhibition or (2) an EPSP that elicited firing. We found that the alpha(2A)-AR agonist guanfacine selectively inhibited this PBN input to the BNST, preferentially reducing the excitatory response in ex vivo mouse brain slices. To begin to assess the overall impact of alpha(2A)-AR control of this PBN input on BNST excitatory transmission, we used a Thy1-COP4 mouse line with little postsynaptic ChR2 expression nor colocalization of ChR2 with CGRP in the BNST. In slices from these mice, we found that guanfacine enhanced, rather than suppressed, optogenetically initiated excitatory drive in BNST. Thus, our study reveals distinct actions of PBN afferents within the BNST and suggests that alpha(2A)-AR agonists may filter excitatory transmission in the BNST by inhibiting a component of the PBN input while enhancing the actions of other inputs.