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Related Experiment Video

Updated: Aug 27, 2025

Investigating Long-term Synaptic Plasticity in Interlamellar Hippocampus CA1 by Electrophysiological Field Recording
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Early life stress impairs synaptic pruning in the developing hippocampus.

Kiran K Dayananda1, Sahabuddin Ahmed1, Daniel Wang1

  • 1Department of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven, CT 06511, USA.

Brain, Behavior, and Immunity
|September 29, 2022
PubMed
Summary

Early life adversity, like limited bedding (LB) or unpredictable postnatal stress (UPS), impairs hippocampal development by affecting microglia and synaptic pruning. This can lead to long-term cognitive and functional deficits.

Keywords:
Early life stressHippocampusLimited bedding and nestingMiceMicrogliaSynaptic pruning

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Psychopathology

Background:

  • Early life adversity negatively impacts hippocampal function and connectivity.
  • The cumulative and dimensional models offer contrasting views on how multiple adversities affect psychopathology risk.
  • Microglia play a crucial role in synaptic pruning during hippocampal development.

Purpose of the Study:

  • To investigate the effects of single (limited bedding) versus multiple (unpredictable postnatal stress) early life adversities on microglia-mediated synaptic pruning in the developing hippocampus.
  • To compare the impact of deprivation (LB) versus a combination of stressors (UPS) on microglial function and synaptic plasticity.
  • To examine the expression of TREM2 and other synaptic pruning genes in response to different early life adversities.

Main Methods:

  • Male and female mice were exposed to limited bedding (LB) or unpredictable postnatal stress (UPS).
  • Microglial ramification, phagocytic activity (in vivo and ex vivo), and TREM2 expression were assessed.
  • Spine density in CA1 pyramidal neurons was analyzed at different developmental stages (17 and 29 days old).
  • Gene expression related to synaptic pruning was measured.

Main Results:

  • Both LB and UPS reduced microglial ramification and phagocytosis, and decreased TREM2 expression.
  • Abnormal microglial activity was associated with increased CA1 pyramidal neuron spine density in both LB and UPS groups.
  • LB induced more severe impairments in microglial function than UPS.
  • UPS exposure led to increased expression of synaptic pruning genes.

Conclusions:

  • Limited bedding (LB) represents a severe form of early deprivation impacting hippocampal development.
  • Adequate hippocampal stimulation during critical developmental weeks is essential for normal microglial function and synaptic pruning.
  • Impaired synaptic pruning during early life contributes to later hippocampal dysfunction observed in both LB and UPS models.