Suppressed Calbindin Levels in Hippocampal Excitatory Neurons Mediate Stress-Induced Memory Loss

• Published in: Cell reports (Cambridge) Vol. 21; no. 4; pp. 891 - 900
• Main Authors: Li, Ji-Tao, Xie, Xiao-Meng, Yu, Jing-Ying, Sun, Ya-Xin, Liao, Xue-Mei, Wang, Xing-Xing, Su, Yun-Ai, Liu, Yi-Jun, Schmidt, Mathias V., Wang, Xiao-Dong, Si, Tian-Mei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.10.2017; Elsevier
• Subjects: Animals; CA1 Region, Hippocampal - cytology; CA1 Region, Hippocampal - metabolism; CA1 Region, Hippocampal - physiology; calbindin; Calbindins - genetics; Calbindins - metabolism; Dentate Gyrus - cytology; Dentate Gyrus - metabolism; Dentate Gyrus - physiology; hippocampus; Interneurons - metabolism; Interneurons - physiology; Male; memory; Memory Disorders - etiology; Memory Disorders - metabolism; Memory, Long-Term; Mice; Mice, Inbred C57BL; nectin3; Nectins - metabolism; Receptors, Corticotropin-Releasing Hormone - metabolism; Spatial Memory; stress; Stress, Psychological - complications; Stress, Psychological - metabolism; calbindin; stress; memory; hippocampus; nectin3
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2017.10.006

Calbindin modulates intracellular Ca2+ dynamics and synaptic plasticity. Reduction of hippocampal calbindin levels has been implicated in early-life stress-related cognitive disorders, but it remains unclear how calbindin in distinct populations of hippocampal neurons contributes to stress-induced memory loss. Here we report that early-life stress suppressed calbindin levels in CA1 and dentate gyrus (DG) neurons, and calbindin knockdown in adult CA1 or DG excitatory neurons mimicked early-life stress-induced memory loss. In contrast, calbindin knockdown in CA1 interneurons preserved long-term memory even after an acute stress challenge. These results indicate that the dysregulation of calbindin in hippocampal excitatory, but not inhibitory, neurons conveys susceptibility to stress-induced memory deficits. Moreover, calbindin levels were downregulated by early-life stress through the corticotropin-releasing hormone receptor 1-nectin3 pathway, which in turn reduced inositol monophosphatase levels. Our findings highlight calbindin as a molecular target of early-life stress and an essential substrate for memory. [Display omitted] •Early-life stress suppresses calbindin levels in the adult mouse hippocampus•Calbindin knockdown in CA1 or DG excitatory neurons impairs spatial memory•Calbindin knockdown in CA1 interneurons preserves long-term spatial memory•Stress downregulates calbindin levels via a corticotropin-releasing hormone receptor Li et al. demonstrate that early-life stress suppresses hippocampal calbindin levels through the CRHR1-nectin3 system. Reduced calbindin levels in hippocampal excitatory, but not inhibitory, neurons mediate stress-induced spatial memory impairment.