Atrophy of pyramidal neurons and increased stress-induced glutamate levels in CA3 following chronic suppression of adult neurogenesis

Robert J. Schloesser, Dennisse V. Jimenez, Nicholas F. Hardy, Daniel Paredes, Briony J. Catlow, Husseini K. Manji, Ronald D. McKay, Keri Martinowich

Research output: Contribution to journalArticle

Abstract

Following their birth in the adult hippocampal dentate gyrus, newborn progenitor cells migrate into the granule cell layer where they differentiate, mature, and functionally integrate into existing circuitry. The hypothesis that adult hippocampal neurogenesis is physiologically important has gained traction, but the precise role of newborn neurons in hippocampal function remains unclear. We investigated whether loss of new neurons impacts dendrite morphology and glutamate levels in area CA3 of the hippocampus by utilizing a human GFAP promoter-driven thymidine kinase genetic mouse model to conditionally suppress adult neurogenesis. We found that chronic ablation of new neurons induces remodeling in CA3 pyramidal cells and increases stress-induced release of the neurotransmitter glutamate. The ability of persistent impairment of adult neurogenesis to influence hippocampal dendrite morphology and excitatory amino acid neurotransmission has important implications for elucidating newborn neuron function, and in particular, understanding the role of these cells in stress-related excitoxicity.

Original languageEnglish (US)
Pages (from-to)1139-1148
Number of pages10
JournalBrain Structure and Function
Volume219
Issue number3
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Pyramidal Cells
Neurogenesis
Atrophy
Glutamic Acid
Neurons
Dendrites
Parahippocampal Gyrus
Excitatory Amino Acids
Thymidine Kinase
Genetic Models
Dentate Gyrus
Traction
Synaptic Transmission
Neurotransmitter Agents
Hippocampus
Stem Cells
Parturition

Keywords

  • Atrophy
  • CA3
  • Dendrite
  • Dentate gyrus
  • Excitotoxicity
  • Neurogenesis

ASJC Scopus subject areas

  • Anatomy
  • Histology
  • Neuroscience(all)
  • Medicine(all)

Cite this

Atrophy of pyramidal neurons and increased stress-induced glutamate levels in CA3 following chronic suppression of adult neurogenesis. / Schloesser, Robert J.; Jimenez, Dennisse V.; Hardy, Nicholas F.; Paredes, Daniel; Catlow, Briony J.; Manji, Husseini K.; McKay, Ronald D.; Martinowich, Keri.

In: Brain Structure and Function, Vol. 219, No. 3, 2014, p. 1139-1148.

Research output: Contribution to journalArticle

Schloesser, Robert J. ; Jimenez, Dennisse V. ; Hardy, Nicholas F. ; Paredes, Daniel ; Catlow, Briony J. ; Manji, Husseini K. ; McKay, Ronald D. ; Martinowich, Keri. / Atrophy of pyramidal neurons and increased stress-induced glutamate levels in CA3 following chronic suppression of adult neurogenesis. In: Brain Structure and Function. 2014 ; Vol. 219, No. 3. pp. 1139-1148.
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