Synaptic competition in the lateral amygdala and the stimulus specificity of conditioned fear: a biophysical modeling study.
Synaptic competition in the lateral amygdala and the stimulus specificity of conditioned fear: a biophysical modeling study.
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DOI：
10.1007/s00429-015-1037-4
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发表时间：
2016-05
影响因子：
3.1
通讯作者：
Nair SS
中科院分区：
文献类型：
--
作者：
Kim D;Samarth P;Feng F;Pare D;Nair SS
竞争性突触之间的相互作用与不同的内在兴奋性的主要神经元（PN）最近被证明，以确定背外侧杏仁核（LAD）神经元被招募到恐惧记忆的痕迹。在这里，我们探讨了这些竞争性的相互作用，在确定条件性恐惧协会的刺激特异性的贡献。为此，我们使用了一个现实的生物物理计算模型的LAD，其中包括多室电导为基础的800 PN和200 interneurons模型。为了重现连续的峰频率适应显示的PN，该模型包括三个亚型的PN与高，中，低的峰频率适应。此外，该模型网络集成了LA内的兴奋性和抑制性连接的空间差异模式，多巴胺能和去甲肾上腺素能输入，外部丘脑和皮质音传入，以模拟条件刺激以及非条件刺激的休克输入。最后，模型中的谷氨酸能突触可以经历活动依赖性可塑性。我们的研究结果表明，在兴奋性（PN-PN）和双突触抑制（PN-ITN，特别是ITN-PN）连接的可塑性是主要的决定因素的突触竞争管理分配的PN的记忆痕迹。该模型还显示，训练诱导的增强PN-PN突触促进，而ITN-PN突触反对，刺激泛化。事实上，抑制PN-PN突触的可塑性增加，而阻止神经元间突触的可塑性降低了PN募集的CS特异性。总的来说，我们的研究结果表明，突触竞争在网络中留下的可塑性配置确保了记忆的特异性。鉴于焦虑症的特点是倾向于将习得性恐惧推广到安全的刺激或情况，了解内在的LAD突触的可塑性如何调节习得性恐惧的特异性是未来实验研究的重要挑战。
Competitive synaptic interactions between principal neurons (PNs) with differing intrinsic excitability were recently shown to determine which dorsal lateral amygdala (LAd) neurons are recruited into a fear memory trace. Here, we explored the contribution of these competitive interactions in determining the stimulus specificity of conditioned fear associations. To this end, we used a realistic biophysical computational model of LAd that included multi-compartment conductance-based models of 800 PNs and 200 interneurons. To reproduce the continuum of spike frequency adaptation displayed by PNs, the model included three subtypes of PNs with high, intermediate, and low spike frequency adaptation. In addition, the model network integrated spatially differentiated patterns of excitatory and inhibitory connections within LA, dopaminergic and noradrenergic inputs, extrinsic thalamic and cortical tone afferents to simulate conditioned stimuli as well as shock inputs for the unconditioned stimulus. Last, glutamatergic synapses in the model could undergo activity-dependent plasticity. Our results suggest that plasticity at both excitatory (PN–PN) and di-synaptic inhibitory (PN–ITN and, particularly, ITN–PN) connections are major determinants of the synaptic competition governing the assignment of PNs to the memory trace. The model also revealed that training-induced potentiation of PN–PN synapses promotes, whereas that of ITN–PN synapses opposes, stimulus generalization. Indeed, suppressing plasticity of PN–PN synapses increased, whereas preventing plasticity of interneuronal synapses decreased the CS specificity of PN recruitment. Overall, our results indicate that the plasticity configuration imprinted in the network by synaptic competition ensures memory specificity. Given that anxiety disorders are characterized by tendency to generalize learned fear to safe stimuli or situations, understanding how plasticity of intrinsic LAd synapses regulates the specificity of learned fear is an important challenge for future experimental studies.