PMID- 23284764
OWN - NLM
STAT- MEDLINE
DCOM- 20130617
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 12
DP  - 2012
TI  - Pannexin1 stabilizes synaptic plasticity and is needed for learning.
PG  - e51767
LID - 10.1371/journal.pone.0051767 [doi]
LID - e51767
AB  - Pannexin 1 (Panx1) represents a class of vertebrate membrane channels, bearing 
      significant sequence homology with the invertebrate gap junction proteins, the 
      innexins and more distant similarities in the membrane topologies and 
      pharmacological sensitivities with gap junction proteins of the connexin family. 
      In the nervous system, cooperation among pannexin channels, adenosine receptors, 
      and K(ATP) channels modulating neuronal excitability via ATP and adenosine has 
      been recognized, but little is known about the significance in vivo. However, the 
      localization of Panx1 at postsynaptic sites in hippocampal neurons and astrocytes 
      in close proximity together with the fundamental role of ATP and adenosine for 
      CNS metabolism and cell signaling underscore the potential relevance of this 
      channel to synaptic plasticity and higher brain functions. Here, we report 
      increased excitability and potently enhanced early and persistent LTP responses 
      in the CA1 region of acute slice preparations from adult Panx1(-/-) mice. 
      Adenosine application and N-methyl-D-aspartate receptor (NMDAR)-blocking 
      normalized this phenotype, suggesting that absence of Panx1 causes chronic 
      extracellular ATP/adenosine depletion, thus facilitating postsynaptic NMDAR 
      activation. Compensatory transcriptional up-regulation of metabotropic glutamate 
      receptor 4 (grm4) accompanies these adaptive changes. The physiological 
      modification, promoted by loss of Panx1, led to distinct behavioral alterations, 
      enhancing anxiety and impairing object recognition and spatial learning in 
      Panx1(-/-) mice. We conclude that ATP release through Panx1 channels plays a 
      critical role in maintaining synaptic strength and plasticity in CA1 neurons of 
      the adult hippocampus. This result provides the rationale for in-depth analysis 
      of Panx1 function and adenosine based therapies in CNS disorders.
FAU - Prochnow, Nora
AU  - Prochnow N
AD  - Neuroanatomy, Medical Faculty, Ruhr-University Bochum, Bochum, Germany.
FAU - Abdulazim, Amr
AU  - Abdulazim A
FAU - Kurtenbach, Stefan
AU  - Kurtenbach S
FAU - Wildforster, Verena
AU  - Wildforster V
FAU - Dvoriantchikova, Galina
AU  - Dvoriantchikova G
FAU - Hanske, Julian
AU  - Hanske J
FAU - Petrasch-Parwez, Elisabeth
AU  - Petrasch-Parwez E
FAU - Shestopalov, Valery I
AU  - Shestopalov VI
FAU - Dermietzel, Rolf
AU  - Dermietzel R
FAU - Manahan-Vaughan, Denise
AU  - Manahan-Vaughan D
FAU - Zoidl, Georg
AU  - Zoidl G
LA  - eng
GR  - EY021517/EY/NEI NIH HHS/United States
GR  - CAPMC/CIHR/Canada
GR  - EY017991/EY/NEI NIH HHS/United States
GR  - R21 EY017991/EY/NEI NIH HHS/United States
GR  - R01 EY021517/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121220
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Connexins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Panx1 protein, mouse)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
EIN - PLoS One. 2013;8(1). doi:10.1371/annotation/d0972416-5fef-4f89-9c09-cb4cb0c6295d
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Anxiety
MH  - Astrocytes/cytology/*metabolism
MH  - Blotting, Western
MH  - Connexins/*physiology
MH  - Electrophysiology
MH  - Female
MH  - Fluorescent Antibody Technique
MH  - Hippocampus/cytology/*metabolism
MH  - Immunoenzyme Techniques
MH  - Learning/*physiology
MH  - Long-Term Potentiation
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Nerve Tissue Proteins/*physiology
MH  - Neurons/cytology/*metabolism
MH  - RNA, Messenger/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Recognition, Psychology/physiology
MH  - Reflex, Startle/physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Synaptic Transmission/*physiology
PMC - PMC3527502
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/01/04 06:00
MHDA- 2013/06/19 06:00
PMCR- 2012/12/20
CRDT- 2013/01/04 06:00
PHST- 2012/08/02 00:00 [received]
PHST- 2012/11/07 00:00 [accepted]
PHST- 2013/01/04 06:00 [entrez]
PHST- 2013/01/04 06:00 [pubmed]
PHST- 2013/06/19 06:00 [medline]
PHST- 2012/12/20 00:00 [pmc-release]
AID - PONE-D-12-23109 [pii]
AID - 10.1371/journal.pone.0051767 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(12):e51767. doi: 10.1371/journal.pone.0051767. Epub 2012 Dec 20.