BACKGROUND Basolateral amygdalar projections to the prefrontal cortex play a key role in modulating behavioral responses to stress stimuli. Among the different neuromodulators known to impact basolateral amygdalar-prefrontal cortex transmission, the corticotrophin releasing factor (CRF) is of particular interest because of its role in modulating anxiety and stress-associated behaviors. While CRF type 1 receptor (CRFR1) has been involved in prefrontal cortex functioning, the participation of CRF type 2 receptor (CRFR2) in basolateral amygdalar-prefrontal cortex synaptic transmission remains unclear. METHODS Immunofluorescence anatomical studies using rat prefrontal cortex synaptosomes devoid of postsynaptic elements were performed in rats with intra basolateral amygdalar injection of biotinylated dextran amine. In vivo microdialysis and local field potential recordings were used to measure glutamate extracellular levels and changes in long-term potentiation in prefrontal cortex induced by basolateral amygdalar stimulation in the absence or presence of CRF receptor antagonists. RESULTS We found evidence for the presynaptic expression of CRFR2 protein and mRNA in prefrontal cortex synaptic terminals originated from basolateral amygdalar. By means of microdialysis and electrophysiological recordings in combination with an intra-prefrontal cortex infusion of the CRFR2 antagonist antisauvagine-30, we were able to determine that CRFR2 is functionally positioned to limit the strength of basolateral amygdalar transmission to the prefrontal cortex through presynaptic inhibition of glutamate release. CONCLUSIONS Our study shows for the first time to our knowledge that CRFR2 is expressed in basolateral amygdalar afferents projecting to the prefrontal cortex and exerts an inhibitory control of prefrontal cortex responses to basolateral amygdalar inputs. Thus, changes in CRFR2 signaling are likely to disrupt the functional connectivity of the basolateral amygdalar-prefrontal cortex pathway and associated behavioral responses.

中文翻译：

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通过局部促肾上腺皮质激素2型受体抑制基底外侧杏仁核传递至前额叶皮层。

背景技术到前额叶皮层的基底外侧杏仁核突起在调节对应激刺激的行为反应中起关键作用。在已知会影响基底外侧杏仁核-前额叶皮层传递的不同神经调节剂中，促肾上腺皮质激素释放因子（CRF）因其在调节焦虑和与压力相关的行为中的作用而特别受关注。虽然CRF 1型受体（CRFR1）已参与额叶前额叶的功能，但CRF 2型受体（CRFR2）是否参与基底外侧杏仁核-前额叶皮质突触传递尚不清楚。方法在大鼠侧外侧杏仁核内注射生物素化的右旋糖酐胺的大鼠中，使用了不含突触后成分的大鼠前额叶皮层突触小体进行了免疫荧光解剖学研究。在不存在或存在CRF受体拮抗剂的情况下，使用体内微透析和局部场电位记录来测量谷氨酸胞外水平和基底外侧杏仁核刺激所诱导的前额叶皮层中长期增强的变化。结果我们发现了起源于基底外侧杏仁核的前额叶皮质突触末端中CRFR2蛋白和mRNA突触前表达的证据。通过微透析和电生理记录，结合前额叶皮质内输注CRFR2拮抗剂antisauvagine-30，我们能够确定CRFR2在功能上的位置，可以通过突触前抑制CFR2限制基底外侧杏仁核向前额皮层的传播强度。谷氨酸释放。结论我们的研究首次显示我们的知识，CRFR2在投射到额前皮层的基底外侧杏仁核传入神经中表达，并抑制额叶皮层对基底外侧杏仁核输入的反应。因此，CRFR2信号的变化可能会破坏基底外侧杏仁核-前额叶皮层通路和相关行为反应的功能连接。