Yoo S-W, Bae M, Tovar-Y-Romo L B, Haughey N J
Department of Neurology, Richard T. Johnson Division of Neuroimmunology and Neurological Infections, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Transl Psychiatry. 2017 Jan 3;7(1):e991. doi: 10.1038/tp.2016.254.
Rodent models of auditory fear conditioning are often used to understand the molecular mechanisms regulating fear- and anxiety-related behaviors. Conditioning and extinction memories are influenced by contextual cues, and the reinstatement of conditioned fear occurs when the conditioning stimulus is presented in a context different from the extinction context. Although it has been proposed that internal state is a feature of context that could influence extinction, contributions of interoception to conditioning have not been experimentally addressed. Here we use ethanol (EtOH) to show that interoceptive cues are encoded through the hippocampus by mechanisms that involve increased phosphorylation of GluR1 on serine 845, and biophysical alterations in neuronal membranes that facilitate stabilization of surface-located calcium-permeable n-2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid (AMPA) receptor (AMPAR) into membrane microdomains. Conflicting interoceptive cues during extinction and fear relapse testing resulted in a failure to consolidate extinction that was reversed by the administration of AMPAR antagonists immediately following the retrieval cue.
听觉恐惧条件反射的啮齿动物模型常用于理解调节恐惧和焦虑相关行为的分子机制。条件反射和消退记忆受情境线索影响，当条件刺激在与消退情境不同的情境中呈现时，条件恐惧会恢复。尽管有人提出内部状态是情境的一个特征，可能影响消退，但内感受对条件反射的贡献尚未得到实验研究。在这里，我们使用乙醇（EtOH）表明，内感受线索通过海马体编码，其机制包括丝氨酸845上的GluR1磷酸化增加，以及神经元膜的生物物理改变，这些改变有助于将位于表面的钙通透性n-2-氨基-3-（5-甲基-3-氧代-1,2-恶唑-4-基）丙酸（AMPA）受体（AMPAR）稳定到膜微区。在消退和恐惧复发测试期间相互冲突的内感受线索导致消退巩固失败，在检索线索后立即给予AMPAR拮抗剂可逆转这种失败。
