Suppressed Calbindin Levels in Hippocampal Excitatory Neurons Mediate Stress-Induced Memory Loss
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 m...
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Published in | Cell reports (Cambridge) Vol. 21; no. 4; pp. 891 - 900 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
24.10.2017
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | 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.
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•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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2211-1247 2211-1247 |
DOI: | 10.1016/j.celrep.2017.10.006 |