Synaptic Targeting of Double-Projecting Ventral CA1 Hippocampal Neurons to the Medial Prefrontal Cortex and Basal Amygdala

Synaptic Targeting of Double-Projecting Ventral CA1 Hippocampal Neurons to the Medial Prefrontal Cortex and Basal Amygdala
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DOI:
10.1523/jneurosci.3579-16.2017
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发表时间:
2017-05-10
影响因子:
5.3
通讯作者:
Cho, Jun-Hyeong
Cho, Jun-Hyeong
中科院分区:
医学1区
文献类型:
--
作者:
Kim, Woong Bin;Cho, Jun-Hyeong

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情境恐惧记忆的获得和提取需要海马体、内侧前额叶皮质(mPFC)和杏仁核的协调神经活动。海马体中编码的情境信息被传递到mPFC和杏仁核,以进行情境恐惧条件反射。先前的研究表明,腹侧海马(VH)的CA 1神经元群体项目的mPFC和杏仁核,并在条件性恐惧的上下文依赖性控制招募。然而,如何双投射腹侧CA 1海马(vCA 1)神经元调制的mPFC和杏仁核在突触水平的活动尚未确定以前。在这里,我们表明VH的光遗传学沉默阻止了小鼠对背景恐惧记忆的回忆,表明其在背景恐惧表达中的作用。在双重逆行病毒追踪和c-Fos免疫染色实验中,我们发现,一部分vCA 1神经元投射到mPFC和杏仁核,并在上下文暴露期间优先招募,这表明它们在编码上下文表征中的作用。此外,光遗传学刺激的轴突侧支的双投射vCA 1神经元诱导单突触兴奋性反应的mPFC和基底杏仁核,表明它们可以通过VH-mPFC和VH-杏仁核途径传递上下文信息。双投射vCA 1神经元的激活也诱导了投射到杏仁核的mPFC神经元的动作电位放电,这表明它们也可以激活VH-mPFC-杏仁核通路。通过这些突触机制,双投射vCA 1神经元可以诱导mPFC和杏仁核中的同步神经活动,并有效地将上下文信息传递到基底杏仁核以进行上下文恐惧条件反射。
The acquisition and retrieval of contextual fear memory requires coordinated neural activity in the hippocampus, medial prefrontal cortex (mPFC), and amygdala. The contextual information encoded in the hippocampus is conveyed to the mPFC and amygdala for contextual fear conditioning. Previous studies have suggested that a CA1 neuronal population in the ventral hippocampus (VH) projects to both the mPFC and amygdala and is recruited in context-dependent control of conditioned fear. However, how double-projecting ventral CA1 hippocampal (vCA1) neurons modulate the activity of the mPFC and amygdala at the synaptic level has not been determined previously. Here, we show that the optogenetic silencing of the VH prevented the recall of contextual fear memory in mice, indicating its role in contextual fear expression. In dual retrograde viral tracing and c-Fos immunostaining experiments, we found that a proportion of vCA1 neurons projected to both the mPFC and amygdala and were recruited preferentially during context exposure, suggesting their role in encoding context representations. Moreover, optogenetic stimulation of axon collaterals of double-projecting vCA1 neurons induced monosynaptic excitatory responses in both the mPFC and basal amygdala, indicating that they could convey contextual information through the VH-mPFC and VH-amygdala pathways. The activation of double-projecting vCA1 neurons also induced action potential firings in the mPFC neurons that project to the amygdala, suggesting that they can also activate the VH-mPFC-amygdala pathway. With these synaptic mechanisms, double-projecting vCA1 neurons could induce synchronized neural activity in the mPFC and amygdala and convey contextual information efficiently to the basal amygdala for contextual fear conditioning.