PMID- 17264839
OWN - NLM
STAT- MEDLINE
DCOM- 20070828
LR  - 20191210
IS  - 1359-4184 (Print)
IS  - 1476-5578 (Electronic)
IS  - 1359-4184 (Linking)
VI  - 12
IP  - 7
DP  - 2007 Jul
TI  - Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and 
      extinction of aversive memories.
PG  - 656-70
AB  - 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.
FAU - Heldt, S A
AU  - Heldt SA
AD  - Department of Psychiatry and Behavioral Sciences, Emory University School of 
      Medicine, Atlanta, GA, USA.
FAU - Stanek, L
AU  - Stanek L
FAU - Chhatwal, J P
AU  - Chhatwal JP
FAU - Ressler, K J
AU  - Ressler KJ
LA  - eng
GR  - T32 GM008169/GM/NIGMS NIH HHS/United States
GR  - MH069884/MH/NIMH NIH HHS/United States
GR  - P51 RR000165/RR/NCRR NIH HHS/United States
GR  - R01 DA019624-01A2/DA/NIDA NIH HHS/United States
GR  - K01 MH069884/MH/NIMH NIH HHS/United States
GR  - P51RR000165/RR/NCRR NIH HHS/United States
GR  - R01 DA019624/DA/NIDA NIH HHS/United States
GR  - F30 MH070218/MH/NIMH NIH HHS/United States
GR  - MH070218/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20070130
PL  - England
TA  - Mol Psychiatry
JT  - Molecular psychiatry
JID - 9607835
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Animals
MH  - Avoidance Learning/*physiology
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Extinction, Psychological/*physiology
MH  - Fear/physiology
MH  - Gene Deletion
MH  - Gene Targeting
MH  - Hippocampus/*metabolism/physiopathology
MH  - Male
MH  - Maze Learning/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - RNA, Messenger/analysis
MH  - Recognition, Psychology/physiology
MH  - Reflex, Startle/physiology
MH  - Spatial Behavior/*physiology
PMC - PMC2442923
MID - NIHMS55848
EDAT- 2007/02/01 09:00
MHDA- 2007/08/29 09:00
PMCR- 2008/07/03
CRDT- 2007/02/01 09:00
PHST- 2007/02/01 09:00 [pubmed]
PHST- 2007/08/29 09:00 [medline]
PHST- 2007/02/01 09:00 [entrez]
PHST- 2008/07/03 00:00 [pmc-release]
AID - 4001957 [pii]
AID - 10.1038/sj.mp.4001957 [doi]
PST - ppublish
SO  - Mol Psychiatry. 2007 Jul;12(7):656-70. doi: 10.1038/sj.mp.4001957. Epub 2007 Jan 
      30.