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

Publication date: 24 October 2017
Source:Cell Reports, Volume 21, Issue 4
Author(s): Ji-Tao Li, Xiao-Meng Xie, Jing-Ying Yu, Ya-Xin Sun, Xue-Mei Liao, Xing-Xing Wang, Yun-Ai Su, Yi-Jun Liu, Mathias V. Schmidt, Xiao-Dong Wang, Tian-Mei Si
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.

Graphical abstract

Teaser

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.


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