Davis Patrick, Zaki Yosif, Maguire Jamie, Reijmers Leon G
Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts, USA.
Medical Scientist Training Program and Graduate Program in Neuroscience, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts, USA.
Nat Neurosci. 2017 Nov;20(11):1624-1633. doi: 10.1038/nn.4651. Epub 2017 Oct 2.
The mammalian brain contains dedicated circuits for both the learned expression and suppression of fear. These circuits require precise coordination to facilitate the appropriate expression of fear behavior, but the mechanisms underlying this coordination remain unclear. Using a combination of chemogenetics, activity-based neuronal-ensemble labeling and in vivo electrophysiology, we found that fear extinction learning confers on parvalbumin-expressing (PV) interneurons in the basolateral amygdala (BLA) a dedicated role in the selective suppression of a previously encoded fear memory and BLA fear-encoding neurons. In addition, following extinction learning, PV interneurons enable a competing interaction between a 6-12 Hz oscillation and a fear-associated 3-6 Hz oscillation within the BLA. Loss of this competition increases a 3-6 Hz oscillatory signature, with BLA→medial prefrontal cortex directionality signaling the recurrence of fear expression. The discovery of cellular and oscillatory substrates of fear extinction learning that critically depend on BLA PV interneurons could inform therapies aimed at preventing the pathological recurrence of fear following extinction learning.
哺乳动物的大脑包含用于习得性恐惧表达和抑制的特定神经回路。这些神经回路需要精确协调以促进恐惧行为的适当表达，但这种协调背后的机制仍不清楚。通过结合化学遗传学、基于活动的神经元群体标记和体内电生理学，我们发现恐惧消退学习赋予基底外侧杏仁核（BLA）中表达小白蛋白（PV）的中间神经元在选择性抑制先前编码的恐惧记忆和BLA恐惧编码神经元方面的特定作用。此外，在消退学习后，PV中间神经元使BLA内6-12赫兹振荡与恐惧相关的3-6赫兹振荡之间产生竞争性相互作用。这种竞争的丧失会增加3-6赫兹振荡特征，BLA→内侧前额叶皮质的方向性表明恐惧表达的复发。对严重依赖BLA PV中间神经元的恐惧消退学习的细胞和振荡底物的发现，可能为旨在防止消退学习后恐惧病理复发的治疗提供信息。
