GluN2D NMDA Receptors Gate Fear Extinction Learning and Interneuron Plasticity.
GluN2D NMDA Receptors Gate Fear Extinction Learning and Interneuron Plasticity.
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DOI：
10.3389/fnsyn.2021.681068
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发表时间：
2021
影响因子：
3.7
通讯作者：
Liu SJ
中科院分区：
文献类型：
--
作者：
Dubois CJ;Liu SJ
小脑在联想恐惧记忆的形成和随后的消退学习中发挥着重要作用。恐惧调节与浦肯野细胞的兴奋性和抑制性突触的长期增强有关。因此，我们测试了恐惧调节是否揭示了新形式的突触可塑性，从而使随后的消退学习能够重置小脑回路。我们发现恐惧学习增强了分子层中间神经元的 GABA 释放，而这种情况在恐惧消退学习后发生了逆转。重要的是，在学习恐惧后，对平行纤维的类似灭绝的刺激足以引起小脑皮层抑制性传导（I-LTDstim）的持续减少，这是一种在幼稚动物中缺乏的可塑性形式。虽然联想记忆的形成和消除需要 NMDA（N-甲基-D-天冬氨酸）受体，但四种主要 NMDA 受体亚基之一的 GluN2D 在学习和记忆中的作用尚未确定。我们发现，如 WT 小鼠所示，恐惧调节会提高 GluN2D KO 中自发 GABA 的释放。然而，GluN2D 的删除消除了学习后平行纤维刺激诱导的 I-LTDstim。在行为水平上，GluN2D亚基的基因缺失并不影响联想学习和记忆保留，但会损害随后的恐惧消退学习。 D-环丝氨酸是一种部分 NMDA 受体 (NMDAR) 激动剂，未能挽救突变小鼠的灭绝学习能力。我们的结果将 GluN2D 确定为灭绝学习的关键 NMDAR 亚基，并揭示了一种与小脑灭绝相关的 GluN2D 依赖性化塑性形式。
The cerebellum is critically involved in the formation of associative fear memory and in subsequent extinction learning. Fear conditioning is associated with a long-term potentiation at both excitatory and inhibitory synapses onto Purkinje cells. We therefore tested whether fear conditioning unmasks novel forms of synaptic plasticity, which enable subsequent extinction learning to reset cerebellar circuitry. We found that fear learning enhanced GABA release from molecular layer interneurons and this was reversed after fear extinction learning. Importantly an extinction-like stimulation of parallel fibers after fear learning is sufficient to induce a lasting decrease in inhibitory transmission (I-LTDstim) in the cerebellar cortex, a form of plasticity that is absent in naïve animals. While NMDA (N-methyl-D-aspartate) receptors are required for the formation and extinction of associative memory, the role of GluN2D, one of the four major NMDA receptor subunits, in learning and memory has not been determined. We found that fear conditioning elevates spontaneous GABA release in GluN2D KO as shown in WT mice. Deletion of GluN2D, however, abolished the I-LTDstim induced by parallel fiber stimulation after learning. At the behavioral level, genetic deletion of GluN2D subunits did not affect associative learning and memory retention, but impaired subsequent fear extinction learning. D-cycloserine, a partial NMDA receptor (NMDAR) agonist, failed to rescue extinction learning in mutant mice. Our results identify GluN2D as a critical NMDAR subunit for extinction learning and reveal a form of GluN2D-dependent metaplasticity that is associated with extinction in the cerebellum.
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影响因子：
4.4
作者：
Alsaad HA;DeKorver NW;Mao Z;Dravid SM;Arikkath J;Monaghan DT
通讯作者：
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DOI：
10.1113/jphysiol.2013.267864
发表时间：
2014-05-15
期刊：
The Journal of physiology
影响因子：
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作者：
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通讯作者：
Gibb AJ
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影响因子：
16.6
作者：
Dubois CJ;Fawcett-Patel J;Katzman PA;Liu SJ
通讯作者：
Liu SJ
影响因子：
2.8
作者：
AITKIN, LM;BOYD, J
通讯作者：
BOYD, J
DOI：
10.1016/0169-328x(95)00107-4
发表时间：
1995-10-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
IKEDA, K;ARAKI, K;MISHINA, M
通讯作者：
MISHINA, M