AhR Deletion Promotes Aberrant Morphogenesis and Synaptic Activity of Adult-Generated Granule Neurons and Impairs Hippocampus-Dependent Memory

eNeuro. 2018 Aug 22;5(4):ENEURO.0370-17.2018. doi: 10.1523/ENEURO.0370-17.2018. eCollection 2018 Jul-Aug.

Abstract

Newborn granule cells are continuously produced in the subgranular zone of dentate gyrus throughout life. Once these cells mature, they integrate into pre-existing circuits modulating hippocampus-dependent memory. Subsequently, mechanisms controlling generation and maturation of newborn cells are essential for proper hippocampal function. Therefore, we have studied the role of aryl hydrocarbon receptor (AhR), a ligand-activated bHLH-PAS transcription factor, in hippocampus-dependent memory and granule neuronal morphology and function using genetic loss-of-function approaches based on constitutive and inducible-nestin AhR-/- mice. The results presented here show that the impaired hippocampus-dependent memory in AhR absence is not due to its effects on neurogenesis but to aberrant dendritic arborization and an increased spine density, albeit with a lower number of mature mushrooms spines in newborn granule cells, a finding that is associated with an immature electrophysiological phenotype. Together, our data strongly suggest that AhR plays a pivotal role in the regulation of hippocampal function, by controlling hippocampal granule neuron morphology and synaptic maturation.

Keywords: Aryl hydrocarbon receptor; dendrite arborization; hippocampal memory; newborn granule cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / deficiency
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Dendritic Spines / physiology*
  • Dentate Gyrus / cytology*
  • Dentate Gyrus / physiopathology*
  • Male
  • Memory Disorders* / genetics
  • Memory Disorders* / pathology
  • Memory Disorders* / physiopathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Morphogenesis / physiology*
  • Neurogenesis / physiology*
  • Neuronal Plasticity / physiology*
  • Receptors, Aryl Hydrocarbon / deficiency
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / physiology*

Substances

  • Ahr protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Receptors, Aryl Hydrocarbon