Contextual fear response is modulated by M-type K+ channels and is associated with subtle structural changes of the axon initial segment in hippocampal GABAergic neurons.

IF 3.1 Q2 NEUROSCIENCES AIMS Neuroscience Pub Date : 2023-01-01 DOI:10.3934/Neuroscience.2023003
Sara Arciniegas Ruiz, Eliav Tikochinsky, Vardit Rubovitch, Chaim G Pick, Bernard Attali
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Abstract

Background: In the fear memory network, the hippocampus modulates contextual aspects of fear learning while mutual connections between the amygdala and the medial prefrontal cortex are widely involved in fear extinction. G-protein-coupled receptors (GPCRs) are involved in the regulation of fear and anxiety, so the regulation of GPCRs in fear signaling pathways can modulate the mechanisms of fear memory acquisition, consolidation and extinction. Various studies suggested a role of M-type K+ channels in modulating fear expression and extinction, although conflicting data prevented drawing of clear conclusions. In the present work, we examined the impact of M-type K+ channel blockade or activation on contextual fear acquisition and extinction. In addition, regarding the pivotal role of the hippocampus in contextual fear conditioning (CFC) and the involvement of the axon initial segment (AIS) in neuronal plasticity, we investigated whether structural alterations of the AIS in hippocampal neurons occurred during contextual fear memory acquisition and short-time extinction in mice in a behaviorally relevant context.

Results: When a single systemic injection of the M-channel blocker XE991 (2 mg/kg, IP) was carried out 15 minutes before the foot shock session, fear expression was significantly reduced. Expression of c-Fos was increased following CFC, mostly in GABAergic neurons at day 1 and day 2 post-fear training in CA1 and dentate gyrus hippocampal regions. A significantly longer AIS segment was observed in GABAergic neurons of the CA1 hippocampal region at day 2.

Conclusions: Our results underscore the role of M-type K + channels in CFC and the importance of hippocampal GABAergic neurons in fear expression.

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情境恐惧反应受m型K+通道调节,与海马gaba能神经元轴突初始段的细微结构变化有关。
背景:在恐惧记忆网络中,海马体调节恐惧学习的情境方面,而杏仁核和内侧前额叶皮层之间的相互连接广泛参与恐惧消退。g蛋白偶联受体(gpcr)参与恐惧和焦虑的调节,因此gpcr在恐惧信号通路中的调节可以调节恐惧记忆的获得、巩固和消退机制。各种研究表明m型K+通道在调节恐惧表达和消退中的作用,尽管相互矛盾的数据阻碍了得出明确的结论。在本研究中,我们研究了m型K+通道阻断或激活对情境恐惧习得和消除的影响。此外,针对海马在情境恐惧条件反射(CFC)中的关键作用以及轴突初始段(AIS)在神经元可塑性中的参与,我们研究了在行为相关情境下小鼠情境恐惧记忆获得和短时消退过程中,海马神经元AIS的结构改变是否发生。结果:在足部休克前15分钟单次全身注射m通道阻滞剂XE991 (2 mg/kg, IP),恐惧表达明显减少。CFC后c-Fos的表达增加,主要在CA1和齿状回海马区的gaba能神经元中表达。第2天,海马CA1区gaba能神经元的AIS段明显延长。结论:我们的研究结果强调了m型K +通道在CFC中的作用,以及海马gaba能神经元在恐惧表达中的重要性。
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来源期刊
AIMS Neuroscience
AIMS Neuroscience NEUROSCIENCES-
CiteScore
4.20
自引率
0.00%
发文量
26
审稿时长
8 weeks
期刊介绍: AIMS Neuroscience is an international Open Access journal devoted to publishing peer-reviewed, high quality, original papers from all areas in the field of neuroscience. The primary focus is to provide a forum in which to expedite the speed with which theoretical neuroscience progresses toward generating testable hypotheses. In the presence of current and developing technology that offers unprecedented access to functions of the nervous system at all levels, the journal is designed to serve the role of providing the widest variety of the best theoretical views leading to suggested studies. Single blind peer review is provided for all articles and commentaries.
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