Chemogenetic Inactivation of Ventral Hippocampal Glutamatergic Neurons Disrupts Consolidation of Contextual Fear Memory
Chemogenetic Inactivation of Ventral Hippocampal Glutamatergic Neurons Disrupts Consolidation of Contextual Fear Memory
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DOI：
10.1038/npp.2014.35
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发表时间：
2014-07-01
影响因子：
7.6
通讯作者：
Roth, Bryan L.
中科院分区：
文献类型：
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作者：
Zhu, Hu;Pleil, Kristen E.;Roth, Bryan L.
突触巩固被认为是巩固大脑记忆的过程。虽然损伤研究主要涉及海马（HPC）在这一过程中，它是未知的细胞类型或区域的HPC可能是必不可少的突触巩固。为了选择性地和可逆地抑制海马神经元的活动在这个过程中，我们开发了一种新的Gi-DREADD（hM 4Di）转基因小鼠在自由移动的动物体内操纵神经元的活动。我们发现，氯氮平-n-氧化物（CNO）可剂量依赖性地使CAI锥体神经元失活。条件性恐惧训练后6 h内海马神经元的失活成功地削弱了背景记忆的巩固，而不干扰线索记忆。为了从解剖学上定义对行为效应至关重要的脑亚区，将hM 4Di病毒载体转导并选择性地在背侧或腹侧HPC中的海马能神经元中表达。值得注意的是，我们发现选择性失活腹侧而不是背侧海马神经元抑制了上下文记忆的突触巩固。
Synaptic consolidation is a process thought to consolidate memory in the brain. Although lesion studies have mainly implicated the hippocampus (HPC) in this process, it is unknown which cell type(s) or regions of the HPC might be essential for synaptic consolidation. To selectively and reversibly suppress hippocampal neuronal activity during this process, we developed a new Gi-DREADD (hM4Di) transgenic mouse for in vivo manipulation of neuronal activity in freely moving animals. We found that CAI pyramidal neurons could be dose-dependently inactivated by clozapine-n-oxide (CNO). Inactivation of hippocampal neurons within 6 h immediately after conditioned fear training successfully impaired the consolidation of contextual memory, without disturbing cued memory. To anatomically define the brain subregion critical for the behavioral effects, hM4Di viral vectors were transduced and selectively expressed in the glutamatergic neurons in either the dorsal or ventral HPC. Significantly, we found that selective inactivation of ventral but not dorsal glutamatergic hippocampal neurons suppressed the synaptic consolidation of contextual memory.