Adult hippocampal neurogenesis modulates fear learning through associative and nonassociative mechanisms

Dong Oh Seo, Mary Ann Carillo, Sean Chih Hsiung Lim, Kenji Tanaka, Michael R. Drew

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Adult hippocampal neurogenesis is believed to support hippocampus-dependent learning and emotional regulation. These putative functions of adult neurogenesis have typically been studied in isolation, and little is known about how they interact to produce adaptive behavior. We used trace fear conditioning as a model system to elucidate mechanisms through which adult hippocampal neurogenesis modulates processing of aversive experience. To achieve a specific ablation of neurogenesis, we generated transgenic mice that express herpes simplex virus thymidine kinase specifically in neural progenitors and immature neurons. Intracerebroventricular injection of the prodrug ganciclovir caused a robust suppression of neurogenesis without suppressing gliogenesis. Neurogenesis ablation via this method or targeted x-irradiation caused an increase in context conditioning in trace but not delay fear conditioning. Data suggest that this phenotype represents opposing effects of neurogenesis ablation on associative and nonassociative components of fear learning. Arrest of neurogenesis sensitizes mice to nonassociative effects of fear conditioning, as evidenced by increased anxiety-like behavior in the open field after (but not in the absence of) fear conditioning. In addition, arrest of neurogenesis impairs associative trace conditioning, but this impairment can be masked by nonassociative fear. The results suggest that adult neurogenesis modulates emotional learning via two distinct but opposing mechanisms: it supports associative trace conditioning while also buffering against the generalized fear and anxiety caused by fear conditioning.

Original languageEnglish
Pages (from-to)11330-11345
Number of pages16
JournalJournal of Neuroscience
Volume35
Issue number32
DOIs
Publication statusPublished - 2015 Aug 12

Fingerprint

Neurogenesis
Fear
Learning
Anxiety
Ganciclovir
Thymidine Kinase
Conditioning (Psychology)
Psychological Adaptation
Prodrugs
Simplexvirus
Transgenic Mice
Hippocampus
Phenotype
Neurons
Injections

Keywords

  • Adult neurogenesis
  • Anxiety
  • Dentate gyrus
  • Doublecortin
  • Fear conditioning
  • Trace conditioning

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Adult hippocampal neurogenesis modulates fear learning through associative and nonassociative mechanisms. / Seo, Dong Oh; Carillo, Mary Ann; Lim, Sean Chih Hsiung; Tanaka, Kenji; Drew, Michael R.

In: Journal of Neuroscience, Vol. 35, No. 32, 12.08.2015, p. 11330-11345.

Research output: Contribution to journalArticle

Seo, Dong Oh ; Carillo, Mary Ann ; Lim, Sean Chih Hsiung ; Tanaka, Kenji ; Drew, Michael R. / Adult hippocampal neurogenesis modulates fear learning through associative and nonassociative mechanisms. In: Journal of Neuroscience. 2015 ; Vol. 35, No. 32. pp. 11330-11345.
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