Cellular Plasticity in the Adult Murine Piriform Cortex: Continuous Maturation of Dormant Precursors Into Excitatory Neurons

Cereb Cortex. 2018 Jul 1;28(7):2610-2621. doi: 10.1093/cercor/bhy087.

Abstract

Neurogenesis in the healthy adult murine brain is based on proliferation and integration of stem/progenitor cells and is thought to be restricted to 2 neurogenic niches: the subventricular zone and the dentate gyrus. Intriguingly, cells expressing the immature neuronal marker doublecortin (DCX) and the polysialylated-neural cell adhesion molecule reside in layer II of the piriform cortex. Apparently, these cells progressively disappear along the course of ageing, while their fate and function remain unclear. Using DCX-CreERT2/Flox-EGFP transgenic mice, we demonstrate that these immature neurons located in the murine piriform cortex do not vanish in the course of aging, but progressively resume their maturation into glutamatergic (TBR1+, CaMKII+) neurons. We provide evidence for a putative functional integration of these newly differentiated neurons as indicated by the increase in perisomatic puncta expressing synaptic markers, the development of complex apical dendrites decorated with numerous spines and the appearance of an axonal initial segment. Since immature neurons found in layer II of the piriform cortex are generated prenatally and devoid of proliferative capacity in the postnatal cortex, the gradual maturation and integration of these cells outside of the canonical neurogenic niches implies that they represent a valuable, but nonrenewable reservoir for cortical plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bromodeoxyuridine / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Cell Plasticity / genetics*
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental / genetics*
  • Glutamate Decarboxylase / metabolism
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Nerve Tissue Proteins / metabolism
  • Neural Cell Adhesion Molecule L1 / metabolism
  • Neurons / physiology*
  • Neuropeptides / genetics
  • Neuropeptides / metabolism
  • Piriform Cortex / cytology*
  • Piriform Cortex / embryology*
  • Sialic Acids / metabolism
  • Stem Cells / physiology*

Substances

  • Dcx protein, mouse
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Neural Cell Adhesion Molecule L1
  • Neuropeptides
  • Sialic Acids
  • enhanced green fluorescent protein
  • polysialyl neural cell adhesion molecule
  • Green Fluorescent Proteins
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1
  • Bromodeoxyuridine