Sagol Department of Neurobiology, University of Haifa, Haifa 31905, Israel.
The Institute for the Study of Affective Neuroscience, University of Haif, Haifa 31905, Israel.
Cereb Cortex. 2018 Jan 1;28(1):395-410. doi: 10.1093/cercor/bhx300.
GABAergic synapses in the basolateral amygdala (BLA) play an important role in fear memory generation. We have previously reported that reduction in GABAergic synapses innervating specifically at the axon initial segment (AIS) of principal neurons of BLA, by neurofascin (NF) knockdown, impairs fear extinction. BLA is bidirectionally connected with the medial prefrontal cortex (mPFC), which is a key region involved in extinction of acquired fear memory. Here, we showed that reducing AIS GABAergic synapses within the BLA leads to impairment of synaptic plasticity in the BLA-mPFC pathway, as well as in the ventral subiculum (vSub)-mPFC pathway, which is independent of BLA involvement. The results suggest that the alteration within the BLA subsequently resulted in a form of trans-regional metaplasticity in the mPFC. In support of that notion, we observed that NF knockdown induced a severe deficit in behavioral flexibility as measured by reversal learning. Interestingly, reversal learning similar to extinction learning is an mPFC-dependent behavior. In agreement with that, measurement of the immediate-early gene, c-Fos immunoreactivity after reversal learning was reduced in the mPFC and BLA, supporting further the notion that the BLA GABAergic manipulation resulted in trans-regional metaplastic alterations within the mPFC.
外侧杏仁核 (BLA) 的 GABA 能突触在恐惧记忆产生中起重要作用。我们之前曾报道过，通过神经束蛋白 (NF) 敲低减少特异性支配 BLA 主神经元轴突起始段 (AIS) 的 GABA 能突触会损害恐惧消退。BLA 与内侧前额叶皮层 (mPFC) 双向连接，mPFC 是参与获得性恐惧记忆消退的关键区域。在这里，我们表明，减少 BLA 内的 AIS GABA 能突触会导致 BLA-mPFC 通路以及腹侧下托 (vSub)-mPFC 通路的突触可塑性受损，而与 BLA 无关。结果表明，BLA 内的改变随后导致 mPFC 内的一种跨区域的后生变化。支持这一观点的是，我们观察到 NF 敲低导致行为灵活性严重缺陷，如反转学习所测量的那样。有趣的是，类似于消退学习的反转学习是一种依赖于 mPFC 的行为。与之一致的是，在反转学习后测量即时早期基因 c-Fos 免疫反应性，发现 mPFC 和 BLA 中的 c-Fos 免疫反应性降低，进一步支持了 BLA GABA 能操作导致 mPFC 内跨区域后生变化的观点。
