Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Centre for Life Sciences (CeLS), Singapore.
Eur J Neurosci. 2013 Aug;38(4):2516-25. doi: 10.1111/ejn.12242. Epub 2013 May 14.
The medial prefrontal cortex (mPFC) in the rat has been implicated in a variety of cognitive processes, including working memory and expression of fear memory. We investigated the inputs from a brain stem nucleus, the nucleus incertus (NI), to the prelimbic area of the mPFC. This nucleus strongly expresses corticotropin-releasing factor type 1 (CRF1 ) receptors and responds to stress. A retrograde tracer was used to verify connections from the NI to the mPFC. Retrogradely labelled cells in the NI expressed CRF receptors. Electrophysiological manipulation of the NI revealed that stimulation of the NI inhibited spontaneous neuronal firing in the mPFC. Similarly, CRF infusion into the NI, in order to mimic a stressful condition, inhibited neuronal firing and burst firing in the mPFC. The effect of concurrent high-frequency stimulation of the NI on plasticity in the hippocampo-prelimbic medial prefrontal cortical (HP-mPFC) pathway was studied. It was found that electrical stimulation of the NI impaired long-term potentiation in the HP-mPFC pathway. Furthermore, CRF infusion into the NI produced similar results. These findings might account for some of the extra-pituitary functions of CRF and indicate that the NI may play a role in stress-driven modulation of working memory and possibly other cognitive processes subserved by the mPFC.
大鼠的内侧前额叶皮层（mPFC）参与了多种认知过程，包括工作记忆和恐惧记忆的表达。我们研究了脑干核团——不确定核（NI）向 mPFC 的额前区的输入。这个核团强烈表达促肾上腺皮质激素释放因子 1 型（CRF1）受体，并对压力做出反应。使用逆行示踪剂来验证从 NI 到 mPFC 的连接。NI 中的逆行标记细胞表达 CRF 受体。NI 的电生理学操作显示，NI 的刺激抑制了 mPFC 中的自发性神经元放电。同样，CRF 注入 NI 以模拟应激条件，抑制了 mPFC 中的神经元放电和爆发放电。同时对 NI 进行高频刺激对海马-额前皮质内侧前额叶皮质（HP-mPFC）通路可塑性的影响进行了研究。结果发现，NI 的电刺激损害了 HP-mPFC 通路中的长时程增强。CRF 注入 NI 也产生了类似的结果。这些发现可能解释了 CRF 的一些垂体外功能，并表明 NI 可能在应激驱动的工作记忆和可能由 mPFC 支持的其他认知过程的调节中发挥作用。
