Reverse engineering information processing in lateral amygdala during auditory tones.
Reverse engineering information processing in lateral amygdala during auditory tones.
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听觉音调期间外侧杏仁核的逆向工程信息处理。
DOI：
10.1109/ner52421.2023.10123856
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Nair,SatishS
中科院分区：
文献类型：
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作者：
Glickert,Greg;Latimer,Ben;Sah,Pankaj;Nair,SatishS
作为联想学习的一种形式，哺乳动物侧杏仁核（LA）在听觉恐惧条件反射过程中的学习需要n -甲基-d -天冬氨酸（NMDA）受体依赖的可塑性。尽管这一事实在二十多年前就已为人所知，但与信号流相关的生物物理细节以及巧合检测器（NMDAR）在这一学习过程中的作用仍不清楚。在这里，我们使用4000个神经元的LA计算模型（包含两种类型的锥体细胞，a型和C型，以及两种类型的中间神经元，快速尖峰FSI和低阈值尖峰LTS）来逆向工程杏仁核中支持这种学习的信息流的变化；特别关注巧合检测器NMDAR的作用。该模型还包括一个基于ca2s的突触可塑性学习规则。生理约束模型为实现音调习惯化的潜在机制提供了见解，包括nmdar在产生网络活动中的作用，该活动在特定传入突触中产生突触可塑性。具体来说，模型运行显示，音调- fsi突触中的NMDARs在自发状态下更为重要，尽管LTS细胞也发挥了作用。只有音调的训练也表明音调- pn突触和音调- fsi突触的长期抑制，这为可能实现习惯化现象的潜在机制提供了可能的假设。
Learning in the mammalian lateral amygdala (LA) during auditory fear conditioning (tone - foot shock pairing), one form of associative learning, requires N-methyl-D-aspartate (NMDA) receptor-dependent plasticity. Despite this fact being known for more than two decades, the biophysical details related to signal flow and the involvement of the coincidence detector, NMDAR, in this learning, remain unclear. Here we use a 4000-neuron computational model of the LA (containing two types of pyramidal cells, types A and C, and two types of interneurons, fast spiking FSI and low-threshold spiking LTS) to reverse engineer changes in information flow in the amygdala that underpin such learning; with a specific focus on the role of the coincidence detector NMDAR. The model also included a Ca2sbased learning rule for synaptic plasticity. The physiologically constrained model provides insights into the underlying mechanisms that implement habituation to the tone, including the role of NMDARs in generating network activity which engenders synaptic plasticity in specific afferent synapses. Specifically, model runs revealed that NMDARs in tone-FSI synapses were more important during the spontaneous state, although LTS cells also played a role. Training trails with tone only also suggested long term depression in tone-PN as well as tone-FSI synapses, providing possible hypothesis related to underlying mechanisms that might implement the phenomenon of habituation.