Chemogenetic Inactivation of Ventral Hippocampal Glutamatergic Neurons Disrupts Consolidation of Contextual Fear Memory

被引:115
作者
Zhu, Hu [1 ]
Pleil, Kristen E. [1 ,2 ]
Urban, Daniel J. [1 ]
Moy, Sheryl S. [3 ,4 ]
Kash, Thomas L. [1 ,2 ]
Roth, Bryan L. [1 ,3 ,5 ,6 ,7 ,8 ]
机构
[1] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Sch Med, Bowles Ctr Alcohol Studies, Dept Pharmacol, Chapel Hill, NC 27599 USA
[3] Univ N Carolina, Carolina Inst Dev Disabil, Chapel Hill, NC 27599 USA
[4] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA
[5] Univ N Carolina, Program Neurosci, Chapel Hill, NC 27599 USA
[6] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
[7] Univ N Carolina, Sch Pharm, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA
[8] Univ N Carolina, NIMH Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA
关键词
LONG-TERM-MEMORY; DIFFERENT ANTEROGRADE AMNESIAS; ANISOMYCIN-INDUCED AMNESIA; 2 TIME WINDOWS; DORSAL HIPPOCAMPUS; ADENYLYL-CYCLASE; BASOLATERAL AMYGDALA; INHIBITORY AVOIDANCE; SYNAPTIC PLASTICITY; MOLECULAR-BIOLOGY;
D O I
10.1038/npp.2014.35
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:1880 / 1892
页数:13
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