Oxytocin excites BNST interneurons and inhibits BNST output neurons to the central amygdala.

Oxytocin excites BNST interneurons and inhibits BNST output neurons to the central amygdala.
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DOI:
10.1016/j.neuropharm.2021.108601
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发表时间:
2021-07-01
期刊:
影响因子:
4.7
通讯作者:
Dabrowska J
Dabrowska J
中科院分区:
医学2区
文献类型:
--
作者:
Francesconi W;Berton F;Olivera-Pasilio V;Dabrowska J

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尾纹背外侧床核(BNSTDL)高表达催产素(OT)受体(OTR),该受体被证明促进了暗示恐惧。然而,OTR在调节BNSTDL活性中的作用仍然难以捉摸。BNSTDL包含gaba -能神经元,根据膜的固有特性分为三种类型。利用膜片钳在雄性大鼠体内的体外记录,我们证明了OT选择性地刺激并增加了I型BNSTDL神经元的自发放电率。因此,OT选择性地增加了II型神经元中自发抑制性突触后电流(sIPSCs)的频率,而不是幅度,这一作用被OTR拮抗剂或河豚毒素所消除,并降低了这些神经元的自发放电率。这些结果表明,OT对II型神经元的间接影响是通过OT诱导的I型中间神经元放电增加来介导的。由于II型BNSTDL神经元被显示向中央杏仁核(CeA)投射,我们也从逆行标记的BNST中记录了含有CeA的神经元,我们显示OT增加了这些II型BNST中sIPSC的频率。相比之下,在III型神经元中,OT降低了sIPSCs的振幅,而不是通过突触后机制诱发IPSCs的频率,而不会改变其固有的兴奋性。我们提出了一种由OT对BNSTDL活性进行微调调节的模型,该模型选择性地兴奋BNSTDL中间神经元并抑制II型BNST《CeA输出神经元》。这些结果表明,BNST中的OTR可能通过抑制BNST中CeA神经元来促进线索恐惧。
The dorsolateral bed nucleus of the stria terminalis (BNSTDL) has high expression of oxytocin (OT) receptors (OTR), which were shown to facilitate cued fear. However, the role of OTR in the modulation of BNSTDL activity remains elusive. BNSTDL contains GABA-ergic neurons classified based on intrinsic membrane properties into three types. Using in vitro patch-clamp recordings in male rats, we demonstrate that OT selectively excites and increases spontaneous firing rate of Type I BNSTDL neurons. As a consequence, OT increases the frequency, but not amplitude, of spontaneous inhibitory post-synaptic currents (sIPSCs) selectively in Type II neurons, an effect abolished by OTR antagonist or tetrodotoxin, and reduces spontaneous firing rate in these neurons. These results suggest an indirect effect of OT in Type II neurons, which is mediated via OT-induced increase in firing of Type I interneurons. As Type II BNSTDL neurons were shown projecting to the central amygdala (CeA), we also recorded from retrogradely labeled BNST➔CeA neurons and we show that OT increases the frequency of sIPSC in these Type II BNST➔CeA output neurons. In contrast, in Type III neurons, OT reduces the amplitude, but not frequency, of both sIPSCs and evoked IPSCs via a postsynaptic mechanism without changing their intrinsic excitability. We present a model of fine-tuned modulation of BNSTDL activity by OT, which selectively excites BNSTDL interneurons and inhibits Type II BNST➔CeA output neurons. These results suggest that OTR in the BNST might facilitate cued fear by inhibiting the BNST➔CeA neurons.
在大鼠和人类中持续的恐惧:恐惧与焦虑中的杏仁核的作用。
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