Fear extinction requires infralimbic cortex projections to the basolateral amygdala.
Fear extinction requires infralimbic cortex projections to the basolateral amygdala.
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DOI：
10.1038/s41398-018-0106-x
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发表时间：
2018-03-06
影响因子：
6.8
通讯作者：
Kash TL
中科院分区：
文献类型：
--
作者：
Bloodgood DW;Sugam JA;Holmes A;Kash TL
恐惧消退涉及形成一种新的记忆痕迹，这种记忆痕迹减弱了对条件厌恶记忆的恐惧反应，而消退障碍与创伤和压力相关的疾病有关。以往在啮齿动物中的研究发现，边缘下前额叶皮层（IL）及其对基底外侧杏仁核（BLA）和基底内侧杏仁核（BMA）的神经元投射指导恐惧消退记忆的形成。然而，目前尚不清楚这些途径是否专门参与灭绝，或者IL的其他主要靶点，如核内神经元（NAc）是否也发挥作用。为了解决这个突出的问题，目前的研究采用了电生理学和化学遗传学方法在小鼠中的组合，以询问IL-BLA和IL-NAc通路在灭绝中的作用。具体来说，我们使用膜片钳电生理加上逆行追踪检查神经元活动的IL和前边缘皮层（PL）的预测BLA和NAC恐惧灭绝后的变化。我们发现，灭绝产生了显着增加的内在兴奋性的IL-BLA投射神经元，而灭绝似乎扭转恐惧引起的变化，IL-NAc投射神经元。为了建立与这些观察结果的因果对应，我们随后使用通路特异性设计者受体专门由设计者药物激活（DREADD）策略来选择性地抑制消退采集期间的PFC-BLA投射神经元。使用这种方法，我们发现，DREADD介导的抑制PFC-BLA神经元在灭绝收购损害随后的灭绝检索。综上所述，我们的研究结果为IL-BLA神经回路对恐惧消退的关键贡献提供了进一步的证据。
Fear extinction involves the formation of a new memory trace that attenuates fear responses to a conditioned aversive memory, and extinction impairments are implicated in trauma- and stress-related disorders. Previous studies in rodents have found that the infralimbic prefrontal cortex (IL) and its glutamatergic projections to the basolateral amygdala (BLA) and basomedial amygdala (BMA) instruct the formation of fear extinction memories. However, it is unclear whether these pathways are exclusively involved in extinction, or whether other major targets of the IL, such as the nucleus accumbens (NAc) also play a role. To address this outstanding issue, the current study employed a combination of electrophysiological and chemogenetic approaches in mice to interrogate the role of IL-BLA and IL-NAc pathways in extinction. Specifically, we used patch-clamp electrophysiology coupled with retrograde tracing to examine changes in neuronal activity of the IL and prelimbic cortex (PL) projections to both the BLA and NAc following fear extinction. We found that extinction produced a significant increase in the intrinsic excitability of IL-BLA projection neurons, while extinction appeared to reverse fear-induced changes in IL-NAc projection neurons. To establish a causal counterpart to these observations, we then used a pathway-specific Designer Receptors Exclusively Activated by Designer Drugs (DREADD) strategy to selectively inhibit PFC-BLA projection neurons during extinction acquisition. Using this approach, we found that DREADD-mediated inhibition of PFC-BLA neurons during extinction acquisition impaired subsequent extinction retrieval. Taken together, our findings provide further evidence for a critical contribution of the IL-BLA neural circuit to fear extinction.
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影响因子：
3
作者：
Arruda-Carvalho M;Clem RL
通讯作者：
Clem RL
DOI：
10.1523/jneurosci.5973-10.2011
发表时间：
2011-02-23
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Muschamp JW;Van't Veer A;Parsegian A;Gallo MS;Chen M;Neve RL;Meloni EG;Carlezon WA Jr
通讯作者：
Carlezon WA Jr
影响因子：
5.3
作者：
Augur, Isabel F.;Wyckoff, Andrew R.;Peters, Jamie
通讯作者：
Peters, Jamie
影响因子：
16.2
作者：
Asede, Douglas;Bosch, Daniel;Ehrlich, Ingrid
通讯作者：
Ehrlich, Ingrid
影响因子：
16.2
作者：
Senn, Verena;Wolff, Steffen B. E.;Luethi, Andreas
通讯作者：
Luethi, Andreas