Induction of hippocampal long-term potentiation increases the morphological dynamics of microglial processes and prolongs their contacts with dendritic spines

Sci Rep. 2016 Sep 8:6:32422. doi: 10.1038/srep32422.

Abstract

Recently microglia, the resident immune cells of the brain, have been recognized as multi-tasking talents that are not only essential in the diseased brain, but also actively contribute to synaptic circuit remodeling during normal brain development. It is well established that microglia dynamically scan their environment and thereby establish transient physical contacts with neuronal synapses, which may allow them to sense and influence synaptic function. However, it is unknown whether and how the morphological dynamics of microglia and their physical interactions with synapses are affected by the induction of synaptic plasticity in the adult brain. To this end, we characterized the morphological dynamics of microglia and their interactions with synapses before and after the induction of synaptic plasticity (LTP) in the hippocampus by time-lapse two-photon imaging and electrophysiological recordings in acute brain slices. We demonstrate that during hippocampal LTP microglia alter their morphological dynamics by increasing the number of their processes and by prolonging their physical contacts with dendritic spines. These effects were absent in the presence of an NMDA receptor antagonist. Taken together, this altered behavior could reflect an active microglial involvement in circuit remodeling during activity-dependent synaptic plasticity in the healthy adult brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Communication
  • Dendritic Spines / drug effects
  • Dendritic Spines / physiology*
  • Dendritic Spines / ultrastructure
  • Electric Stimulation / methods
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • Female
  • Gene Expression
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Male
  • Mice
  • Mice, Knockout
  • Microglia / cytology
  • Microglia / drug effects
  • Microglia / physiology*
  • Microtomy
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synapses / drug effects
  • Synapses / physiology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Time-Lapse Imaging / methods
  • Tissue Culture Techniques
  • Valine / analogs & derivatives
  • Valine / pharmacology

Substances

  • Receptors, N-Methyl-D-Aspartate
  • 2-amino-5-phosphopentanoic acid
  • Valine