Effects of optogenetic photoexcitation of infralimbic cortex inputs to the basolateral amygdala on conditioned fear and extinction.
Effects of optogenetic photoexcitation of infralimbic cortex inputs to the basolateral amygdala on conditioned fear and extinction.
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DOI：
10.1016/j.bbr.2020.112913
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发表时间：
2021-01-01
影响因子：
2.7
通讯作者：
Holmes A
中科院分区：
文献类型：
--
作者：
Bukalo O;Nonaka M;Weinholtz CA;Mendez A;Taylor WW;Holmes A
在消除恐惧的能力上的防御是创伤和压力相关障碍、焦虑症和某些其他神经精神疾病的标志。因此，更深入地了解恐惧抑制中的大脑机制具有重要的翻译意义。先前在啮齿动物中的研究表明，从下边缘前额叶皮层（IL）到基底外侧杏仁核（BLA）的脑电投射在灭绝记忆的形成中起着至关重要的指导作用，并且还表明这种输入强度的变化与灭绝功效相关。为了进一步研究IL→BLA通路与消退之间的关系，我们在IL神经元中表达了三种不同滴度的兴奋性视蛋白，通道视紫红质（ChR2），并在部分消退训练期间光刺激它们在BLA中的投射。不同的滴度组的光激发的行为影响：低滴度没有影响，中滴度选择性地促进灭绝记忆的形成，和高滴度产生的急性抑制恐惧和减少恐惧（无光）灭绝检索。我们讨论了这些滴度特异性效应的各种可能的解释，包括在足够强的光激发条件下IL介导的BLA恐惧编码神经元抑制的可能性。这些发现进一步支持了IL→BLA通路在调节恐惧中的作用，并强调了方法因素在行为神经回路光遗传学研究中的重要性。
Deficiencies in the ability to extinguish fear is a hallmark of Trauma- and stressor-related disorders, Anxiety disorders, and certain other neuropsychiatric conditions. Hence, a greater understanding of the brain mechanisms involved in the inhibition of fear is of significant translational relevance. Previous studies in rodents have shown that glutamatergic projections from the infralimbic prefrontal cortex (IL) to basolateral amygdala (BLA) play a crucial instructional role in the formation of extinction memories, and also indicate that variation in the strength of this input correlates with extinction efficacy. To further examine the relationship between the IL→BLA pathway and extinction we expressed three different titers of the excitatory opsin, channelrhodopsin (ChR2), in IL neurons and photostimulated their projections in the BLA during partial extinction training. The behavioral effects of photoexcitation differed across the titer groups: the low titer had no effect, the medium titer selectively facilitated extinction memory formation, and the high titer produced both an acute suppression of fear and a decrease in fear during (light-free) extinction retrieval. We discuss various possible explanations for these titer-specific effects, including the possibility of IL-mediated inhibition of BLA fear-encoding neurons under conditions of sufficiently strong photoexcitation. These findings further support the role of IL→BLA pathway in regulating fear and highlight the importance of methodological factors in optogenetic studies of neural circuits underling behavior.
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