Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memories

Scott Heldt, L. Stanek, J. P. Chhatwal, K. J. Ressler

Research output: Contribution to journalArticle

400 Citations (Scopus)

Abstract

Brain-derived neurotrophic factor (BDNF) is known to play a critical role in the synaptic plasticity underlying the acquisition and/or consolidation of certain forms of memory. Additionally, a role has been suggested for neurotrophin function within the hippocampus in protection from anxiety and depressive disorders. Understanding the function of this important gene in adult animals has been limited however, because standard knockouts are confounded by gene effects during development. There are no BDNF receptor-specific pharmacological agents, and infusions of neuropeptides or antibodies have other significant limitations. In these studies, we injected a lentivirus expressing Cre recombinase bilaterally into the dorsal hippocampus in adult mice floxed at the BDNF locus to facilitate the site-specific deletion of the BDNF gene in adult animals. Significant decreases in BDNF mRNA expression are demonstrated in the hippocampi of lenti-Cre-infected animals compared with control lenti-GFP-infected animals. Behaviorally, there were no significant effects of BDNF deletion on locomotion or baseline anxiety measured with startle. In contrast, hippocampal-specific BDNF deletions impair novel object recognition and spatial learning as demonstrated with the Morris water maze. Although there were no effects on the acquisition or expression fear, animals with BDNF deletions show significantly reduced extinction of conditioned fear as measured both with fear-potentiated startle and freezing. These data suggest that the cognitive deficits and impairment in extinction of aversive memory found in depression and anxiety disorders may be directly related to decreased hippocampal BDNF.

Original languageEnglish (US)
Pages (from-to)656-670
Number of pages15
JournalMolecular Psychiatry
Volume12
Issue number7
DOIs
StatePublished - Jul 23 2007

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Brain-Derived Neurotrophic Factor
Hippocampus
Fear
Anxiety Disorders
trkB Receptor
Lentivirus
Gene Knockout Techniques
Neuronal Plasticity
Spatial Memory
Psychological Extinction
Nerve Growth Factors
Locomotion
Depressive Disorder
Neuropeptides
Freezing
Genes
Anxiety
Pharmacology
Depression
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memories. / Heldt, Scott; Stanek, L.; Chhatwal, J. P.; Ressler, K. J.

In: Molecular Psychiatry, Vol. 12, No. 7, 23.07.2007, p. 656-670.

Research output: Contribution to journalArticle

Heldt, Scott ; Stanek, L. ; Chhatwal, J. P. ; Ressler, K. J. / Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memories. In: Molecular Psychiatry. 2007 ; Vol. 12, No. 7. pp. 656-670.
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