Kim Tae-Kyung, Han Pyung-Lim
Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul 03760, Korea.
Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul 03760, Korea.; Department of Chemistry and Nano Science, Ewha Womans University, Seoul 03760, Korea.
Exp Neurobiol. 2016 Dec;25(6):307-317. doi: 10.5607/en.2016.25.6.307. Epub 2016 Nov 23.
Chronic stress induces changes in neuronal functions in specific brain regions regulating sociability and mood-related behaviors. Recently we reported that stress-induced persistent upregulation of the neuropeptides orexin and melanin-concentrating hormone (MCH) in the basolateral amygdala (BLA) and the resulting activation of orexin receptors or MCH receptors within the BLA produced deficits in sociability and mood-related behaviors. In the present study, we investigated the neural targets that were innervated by BLA neurons containing orexin receptors or MCH receptors. The viral vector system AAV2-CaMKII-ChR2-eYFP was injected into the BLA to trace the axonal tracts of BLA neurons. This axon labeling analysis led us to identify the prelimbic and infralimbic cortices, nucleus accumbens (NAc), dorsal striatum, paraventricular nucleus (PVN), interstitial nucleus of the posterior limb of the anterior commissure, habenula, CA3 pyramidal neurons, central amygdala, and ventral hippocampus as the neuroanatomical sites receiving synaptic inputs of BLA neurons. Focusing on these regions, we then carried out stimulus-dependent c-Fos induction analysis after activating orexin receptors or MCH receptors of BLA neurons. Stereotaxic injection of an orexin receptor agonist or an MCH receptor agonist in the BLA induced c-Fos expression in the NAc, PVN, central amygdala, ventral hippocampus, lateral habenula and lateral hypothalamus, which are all potentially important for depression-related behaviors. Among these neural correlates, the NAc, PVN and central amygdala were strongly activated by stimulation of orexin receptors or MCH receptors in the BLA, whereas other BLA targets were differentially and weakly activated. These results identify a functional connectivity of BLA neurons regulated by orexin and MCH receptor systems in sociability and mood-related behaviors.
慢性应激会诱导特定脑区的神经元功能发生变化，这些脑区调节社交能力和与情绪相关的行为。最近我们报道，应激诱导基底外侧杏仁核（BLA）中神经肽食欲素和促黑素细胞激素（MCH）持续上调，以及BLA内食欲素受体或MCH受体的激活，导致社交能力和与情绪相关行为出现缺陷。在本研究中，我们调查了含有食欲素受体或MCH受体的BLA神经元所支配的神经靶点。将病毒载体系统AAV2-CaMKII-ChR2-eYFP注入BLA，以追踪BLA神经元的轴突束。这种轴突标记分析使我们确定，前边缘皮层、边缘下皮层、伏隔核（NAc）、背侧纹状体、室旁核（PVN）、前连合后肢间质核、缰核、CA3锥体神经元、中央杏仁核和腹侧海马体是接受BLA神经元突触输入的神经解剖学部位。聚焦于这些区域，我们随后在激活BLA神经元的食欲素受体或MCH受体后进行了刺激依赖性c-Fos诱导分析。在BLA中立体定向注射食欲素受体激动剂或MCH受体激动剂，可诱导NAc、PVN、中央杏仁核、腹侧海马体、外侧缰核和外侧下丘脑表达c-Fos，这些区域对与抑郁相关的行为都可能很重要。在这些神经关联中，NAc、PVN和中央杏仁核在BLA中受到食欲素受体或MCH受体刺激时被强烈激活，而其他BLA靶点则被不同程度地微弱激活。这些结果确定了在社交能力和与情绪相关行为中，由食欲素和MCH受体系统调节的BLA神经元的功能连接。
