PMID- 30127343
OWN - NLM
STAT- MEDLINE
DCOM- 20190326
LR  - 20231004
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 43
IP  - 13
DP  - 2018 Dec
TI  - Alteration of BDNF in the medial prefrontal cortex and the ventral hippocampus 
      impairs extinction of avoidance.
PG  - 2636-2644
LID - 10.1038/s41386-018-0176-8 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) is critical for establishing 
      activity-related neural plasticity. There is increasing interest in the 
      mechanisms of active avoidance and its extinction, but little is known about the 
      role of BDNF in these processes. Using the platform-mediated avoidance task 
      combined with local infusions of an antibody against BDNF, we show that blocking 
      BDNF in either prelimbic (PL) or infralimbic (IL) medial prefrontal cortex during 
      extinction training impairs subsequent recall of extinction of avoidance, 
      differing from extinction of conditioned freezing. By combining retrograde 
      tracers with BDNF immunohistochemistry, we show that extinction of avoidance 
      increases BDNF expression in ventral hippocampal (vHPC) neurons, but not amygdala 
      neurons, projecting to PL and IL. Using the CRISPR/Cas9 system, we further show 
      that reducing BDNF production in vHPC neurons impairs recall of avoidance 
      extinction. Thus, the vHPC may mediate behavioral flexibility in avoidance by 
      driving extinction-related plasticity via BDNFergic projections to both PL and 
      IL. These findings add to the growing body of knowledge implicating the 
      hippocampal-prefrontal pathway in anxiety-related disorders and extinction-based 
      therapies.
FAU - Rosas-Vidal, Luis E
AU  - Rosas-Vidal LE
AUID- ORCID: 0000-0002-9849-0161
AD  - Departments of Psychiatry and Anatomy & Neurobiology, School of Medicine, 
      University of Puerto Rico, San Juan, Puerto Rico, USA.
AD  - Department of Psychiatry, Vanderbilt University Medical Center, Nashville, TN, 
      37232, USA.
FAU - Lozada-Miranda, Valeria
AU  - Lozada-Miranda V
AD  - Departments of Psychiatry and Anatomy & Neurobiology, School of Medicine, 
      University of Puerto Rico, San Juan, Puerto Rico, USA.
FAU - Cantres-Rosario, Yisel
AU  - Cantres-Rosario Y
AD  - Department of Microbiology and Medical Zoology, School of Medicine, University of 
      Puerto Rico, San Juan, Puerto Rico, USA.
FAU - Vega-Medina, Alexis
AU  - Vega-Medina A
AD  - Departments of Psychiatry and Anatomy & Neurobiology, School of Medicine, 
      University of Puerto Rico, San Juan, Puerto Rico, USA.
FAU - Melendez, Loyda
AU  - Melendez L
AD  - Department of Microbiology and Medical Zoology, School of Medicine, University of 
      Puerto Rico, San Juan, Puerto Rico, USA.
FAU - Quirk, Gregory J
AU  - Quirk GJ
AD  - Departments of Psychiatry and Anatomy & Neurobiology, School of Medicine, 
      University of Puerto Rico, San Juan, Puerto Rico, USA. gregoryjquirk@gmail.com.
LA  - eng
GR  - U54 MD007600/MD/NIMHD NIH HHS/United States
GR  - R25 GM086262/GM/NIGMS NIH HHS/United States
GR  - SC1 GM113691/GM/NIGMS NIH HHS/United States
GR  - R36 MH106332/MH/NIMH NIH HHS/United States
GR  - P50 MH106435/MH/NIMH NIH HHS/United States
GR  - R37 MH058883/MH/NIMH NIH HHS/United States
GR  - R01 MH058883/MH/NIMH NIH HHS/United States
PT  - Journal Article
DEP - 20180811
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Bdnf protein, rat)
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Animals
MH  - Avoidance Learning/*physiology
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis
MH  - CRISPR-Cas Systems/physiology
MH  - Cell Line, Tumor
MH  - Extinction, Psychological/*physiology
MH  - Hippocampus/*metabolism
MH  - Male
MH  - Neural Pathways/metabolism
MH  - Neuronal Plasticity/*physiology
MH  - Prefrontal Cortex/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC6224579
COIS- The authors declare that they have no conflict of interest.
EDAT- 2018/08/22 06:00
MHDA- 2019/03/27 06:00
PMCR- 2019/12/01
CRDT- 2018/08/22 06:00
PHST- 2017/11/23 00:00 [received]
PHST- 2018/07/24 00:00 [accepted]
PHST- 2018/07/11 00:00 [revised]
PHST- 2018/08/22 06:00 [pubmed]
PHST- 2019/03/27 06:00 [medline]
PHST- 2018/08/22 06:00 [entrez]
PHST- 2019/12/01 00:00 [pmc-release]
AID - 10.1038/s41386-018-0176-8 [pii]
AID - 176 [pii]
AID - 10.1038/s41386-018-0176-8 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2018 Dec;43(13):2636-2644. doi: 
      10.1038/s41386-018-0176-8. Epub 2018 Aug 11.