Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memories
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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.
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Selective BDNF deletion in the mouse hippocampus disrupted NOP memory.
“selective BDNF deletion in the mouse hippocampus disrupted NOP memory”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Heldt et al., 2007
Manipulation of brain-derived neurotrophic factor expression directly impacts upon performance in spatial and contextual memory tasks.
“The importance of BDNF to hippocampal neuroplasticity is epitomized by animal studies, which have found that the manipulation of BDNF expression directly impacts upon performance in spatial and contextual memory tasks (Linnarsson et al., 1997; Alonso et al., 2002; Heldt et al., 2007; Peters et al., 2010), and also that the downregulation of BDNF inhibits AE induced improvements in spatial memory”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Heldt et al., 2007
Hippocampal expression of BDNF is required for the neural plasticity underlying the acquisition or consolidation of extinction memories.
“More recently, Heldt et al (2007) demonstrated that the hippocampal expression of BDNF is required for the neural plasticity underlying the acquisition or consolidation of extinction memories.”
From Effects of Single Prolonged Stress and D-Cycloserine on Contextual Fear Extinction and Hippocampal NMDA Receptor Expression in a Rat Model of PTSD (2008) · cites this paper as Heldt et al (2007)
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- Authors
- Heldt, S. A., Stanek, L., Chhatwal, J. P., & Ressler, K. J.
- Affiliations
- Emory University (US)
- Corresponding author
- Ressler, K J
- Venue
- Molecular Psychiatry
- Published
- 2007-01-30
- Volume
- 12
- Issue
- 7
- Pages
- 656-670
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC2442923
- OpenAlex
- W2047731623
- Cited by
- 684
- References
- 93
- Citations by year
- 2026: 22 · 2025: 18 · 2024: 25 · 2023: 26 · 2022: 40 · 2021: 45 · 2020: 35 · 2019: 37 · 2018: 40 · 2017: 42 · 2016: 40 · 2015: 43 · 2014: 42 · 2013: 38 · 2012: 43
- FWCI
- 17.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (MH069884, F30MH070218, MH070218, K01MH069884)
- National Institute on Drug Abuse (R01DA019624)
- National Institute of General Medical Sciences (T32GM008169)
- National Center for Research Resources (P51RR000165)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- brain-derived neurotrophic factor, hippocampus, gene deletion, spatial memory, fear extinction, fear conditioning, novel object recognition, anxiety, depression, synaptic plasticity
- MeSH terms
- Animals, Avoidance Learning, Extinction, Psychological, Fear, Hippocampus, Male, Mice, Transgenic, RNA, Messenger, Spatial Behavior, Reflex, Startle, Gene Deletion, Mice, Knockout, Gene Targeting, Maze Learning, Brain-Derived Neurotrophic Factor, Recognition, Psychology, Mice
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