The Sagol Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, Israel.
Int J Neuropsychopharmacol. 2013 May;16(4):825-33. doi: 10.1017/S1461145712000636. Epub 2012 Jun 18.
We studied the role of PI3K cascade in the basolateral amygdala (BLA) and the infralimbic region of the medial prefrontal cortex (IL-mPFC), in contextual fear learning and extinction in the rat. To that end, we micro-infused the phosphoinositide-3-kinase (PIK3) inhibitor LY294002 into either the mPFC or the BLA. Infusion of LY294002 into the BLA following fear conditioning was associated with enhanced freezing levels and impaired extinction in the subsequent sessions. Similarly, inhibition of PI3K in the BLA before the retrieval of fear memory was associated with impaired retrieval of the fear memory, which was expressed as reduced freezing levels that persisted over 2 d. In the IL-mPFC, only consolidation of fear extinction was impaired: micro-infusion of PI3K inhibitor following the retrieval of fear was associated with impaired extinction on the following days. These results indicate differences in the temporal parameters of the effects of PI3K inhibition in the IL-mPFC and in the BLA, which suggest differential involvement of these structures in long-term fear and in extinction of fear memory. Our findings provide additional evidence for the critical roles played by PI3K in intact formation of fear memory and in its extinction and add new evidence for a role of PI3K in consolidation of memory of extinction. Better understanding of the differential involvement of the PI3K cascade during acquisition and extinction of fear conditioning in the mPFC-amygdala circuit could potentially contribute to the understanding and treatment of anxiety disorders.
我们研究了磷脂酰肌醇 3-激酶（PI3K）级联在大鼠情景恐惧学习和消退中的背外侧杏仁核（BLA）和内侧前额叶皮层（IL-mPFC）中的作用。为此，我们将磷脂酰肌醇-3-激酶（PI3K）抑制剂 LY294002 微注入 mPFC 或 BLA。在恐惧条件反射后将 LY294002 注入 BLA 与冻结水平升高和随后的消退过程中的消退受损有关。同样，在恐惧记忆检索之前抑制 BLA 中的 PI3K 与恐惧记忆的检索受损有关，这表现为冻结水平降低，持续了 2 天。在 IL-mPFC 中，只有恐惧消退的巩固受到损害：在恐惧的检索后注入 PI3K 抑制剂与随后几天的消退受损有关。这些结果表明 PI3K 抑制在 IL-mPFC 和 BLA 中的作用的时间参数存在差异，这表明这些结构在长期恐惧和恐惧记忆消退中具有不同的参与。我们的研究结果为 PI3K 在完整的恐惧记忆形成及其消退中发挥关键作用提供了额外的证据，并为 PI3K 在消退记忆的巩固中的作用提供了新的证据。更好地了解 PI3K 级联在 mPFC-杏仁核回路中的恐惧条件反射获得和消退过程中的差异参与，可能有助于理解和治疗焦虑症。
