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

Ji-Tao Li1, Xiao-Meng Xie1, Jing-Ying Yu2

  • 1National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital/Institute of Mental Health, 100191 Beijing, China; Key Laboratory of Mental Health, Ministry of Health, Peking University, 100191 Beijing, China.

Cell Reports
|October 26, 2017
PubMed

Insights

Early-life stress reduces calbindin in hippocampal excitatory neurons, impairing memory. Targeting calbindin in these neurons may prevent stress-induced memory loss.

Area of Science:

  • Neuroscience
  • Molecular Biology

Background:

  • Calbindin regulates intracellular calcium and synaptic plasticity.
  • Reduced hippocampal calbindin is linked to cognitive deficits from early-life stress.
  • The specific role of calbindin in different hippocampal neuron types regarding stress-induced memory loss is unclear.

Purpose of the Study:

  • To investigate how calbindin in distinct hippocampal neuron populations affects stress-induced memory loss.
  • To identify the molecular pathways through which early-life stress impacts calbindin levels.

Main Methods:

  • Examined calbindin levels in CA1 and dentate gyrus (DG) neurons after early-life stress.
  • Performed calbindin knockdown in adult CA1 or DG excitatory and inhibitory neurons.
  • Investigated the corticotropin-releasing hormone receptor 1-nectin3 pathway's role.

Main Results:

  • Early-life stress decreased calbindin in CA1 and DG neurons.
  • Calbindin knockdown in excitatory neurons mimicked stress-induced memory deficits.
  • Calbindin knockdown in CA1 interneurons protected memory from acute stress.
  • Stress downregulated calbindin via the CRHR1-nectin3 pathway, reducing inositol monophosphatase.

Conclusions:

  • Calbindin dysregulation in hippocampal excitatory neurons, not inhibitory neurons, mediates susceptibility to stress-induced memory loss.
  • Calbindin is a key molecular target of early-life stress impacting memory formation.
  • The CRHR1-nectin3 pathway is crucial for stress-induced calbindin reduction.

Keywords:
calbindinhippocampusmemorynectin3stress

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