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Release of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala

Jimmy Stehberg, Rodrigo Moraga-Amaro, Christian Salazar, Alvaro Becerra, Cesar Echeverría, Juan A Orellana, Geert Bultynck, Raf Ponsaerts, Luc Leybaert UGent and Felipe Simon, et al. (2012) FASEB JOURNAL. 26(9). p.3649-3657
abstract
Recent in vitro evidence indicates that astrocytes can modulate synaptic plasticity by releasing neuroactive substances (gliotransmitters). However, whether gliotransmitter release from astrocytes is necessary for higher brain function in vivo, particularly for memory, as well as the contribution of connexin (Cx) hemichannels to gliotransmitter release, remain elusive. Here, we microinfused into the rat basolateral amygdala (BLA) TAT-Cx43L2, a peptide that selectively inhibits Cx43-hemichannel opening while maintaining synaptic transmission or interastrocyte gap junctional communication. In vivo blockade of Cx43 hemichannels during memory consolidation induced amnesia for auditory fear conditioning, as assessed 24 h after training, without affecting short-term memory, locomotion, or shock reactivity. The amnesic effect was transitory, specific for memory consolidation, and was confirmed after microinfusion of Gap27, another Cx43-hemichannel blocker. Learning capacity was recovered after coinfusion of TAT-Cx43L2 and a mixture of putative gliotransmitters (glutamate, glutamine, lactate, D-serine, glycine, and ATP). We propose that gliotransmitter release from astrocytes through Cx43 hemichannels is necessary for fear memory consolidation at the BLA. Thus, the present study is the first to demonstrate a physiological role for astroglial Cx43 hemichannels in brain function, making these channels a novel pharmacological target for the treatment of psychiatric disorders, including post-traumatic stress disorder.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
amnesia, astrocyte, gliotransmitters, learning, GAP-JUNCTION HEMICHANNELS, LONG-TERM POTENTIATION, GLUTAMATE RELEASE, SYNAPTIC-TRANSMISSION, CULTURED ASTROCYTES, CORTICAL ASTROCYTES, EXOCYTOTIC RELEASE, GLIAL-CELLS, D-SERINE, ATP
journal title
FASEB JOURNAL
Faseb J.
volume
26
issue
9
pages
3649 - 3657
Web of Science type
Article
Web of Science id
000308391600007
JCR category
BIOLOGY
JCR impact factor
5.704 (2012)
JCR rank
7/83 (2012)
JCR quartile
1 (2012)
ISSN
0892-6638
DOI
10.1096/fj.11-198416
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2950378
handle
http://hdl.handle.net/1854/LU-2950378
date created
2012-06-30 12:11:24
date last changed
2013-07-08 16:41:28
@article{2950378,
  abstract     = {Recent in vitro evidence indicates that astrocytes can modulate synaptic plasticity by releasing neuroactive substances (gliotransmitters). However, whether gliotransmitter release from astrocytes is necessary for higher brain function in vivo, particularly for memory, as well as the contribution of connexin (Cx) hemichannels to gliotransmitter release, remain elusive. Here, we microinfused into the rat basolateral amygdala (BLA) TAT-Cx43L2, a peptide that selectively inhibits Cx43-hemichannel opening while maintaining synaptic transmission or interastrocyte gap junctional communication. In vivo blockade of Cx43 hemichannels during memory consolidation induced amnesia for auditory fear conditioning, as assessed 24 h after training, without affecting short-term memory, locomotion, or shock reactivity. The amnesic effect was transitory, specific for memory consolidation, and was confirmed after microinfusion of Gap27, another Cx43-hemichannel blocker. Learning capacity was recovered after coinfusion of TAT-Cx43L2 and a mixture of putative gliotransmitters (glutamate, glutamine, lactate, D-serine, glycine, and ATP). We propose that gliotransmitter release from astrocytes through Cx43 hemichannels is necessary for fear memory consolidation at the BLA. Thus, the present study is the first to demonstrate a physiological role for astroglial Cx43 hemichannels in brain function, making these channels a novel pharmacological target for the treatment of psychiatric disorders, including post-traumatic stress disorder.},
  author       = {Stehberg, Jimmy and Moraga-Amaro, Rodrigo and Salazar, Christian and Becerra, Alvaro and Echeverr{\'i}a, Cesar and Orellana, Juan A and Bultynck, Geert and Ponsaerts, Raf and Leybaert, Luc and Simon, Felipe and S{\'a}ez, Juan C and Retamal, Mauricio A},
  issn         = {0892-6638},
  journal      = {FASEB JOURNAL},
  keyword      = {amnesia,astrocyte,gliotransmitters,learning,GAP-JUNCTION HEMICHANNELS,LONG-TERM POTENTIATION,GLUTAMATE RELEASE,SYNAPTIC-TRANSMISSION,CULTURED ASTROCYTES,CORTICAL ASTROCYTES,EXOCYTOTIC RELEASE,GLIAL-CELLS,D-SERINE,ATP},
  language     = {eng},
  number       = {9},
  pages        = {3649--3657},
  title        = {Release of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala},
  url          = {http://dx.doi.org/10.1096/fj.11-198416},
  volume       = {26},
  year         = {2012},
}

Chicago
Stehberg, Jimmy, Rodrigo Moraga-Amaro, Christian Salazar, Alvaro Becerra, Cesar Echeverría, Juan A Orellana, Geert Bultynck, et al. 2012. “Release of Gliotransmitters Through Astroglial Connexin 43 Hemichannels Is Necessary for Fear Memory Consolidation in the Basolateral Amygdala.” Faseb Journal 26 (9): 3649–3657.
APA
Stehberg, J., Moraga-Amaro, R., Salazar, C., Becerra, A., Echeverría, C., Orellana, J. A., Bultynck, G., et al. (2012). Release of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala. FASEB JOURNAL, 26(9), 3649–3657.
Vancouver
1.
Stehberg J, Moraga-Amaro R, Salazar C, Becerra A, Echeverría C, Orellana JA, et al. Release of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala. FASEB JOURNAL. 2012;26(9):3649–57.
MLA
Stehberg, Jimmy, Rodrigo Moraga-Amaro, Christian Salazar, et al. “Release of Gliotransmitters Through Astroglial Connexin 43 Hemichannels Is Necessary for Fear Memory Consolidation in the Basolateral Amygdala.” FASEB JOURNAL 26.9 (2012): 3649–3657. Print.