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

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dc.contributor.authorStehberg, Jimmy
dc.contributor.authorMoraga-Amaro, Rodrigo
dc.contributor.authorSalazar, Christian
dc.contributor.authorBecerra, Alvaro
dc.contributor.authorEcheverría, Cesar
dc.contributor.authorOrellana, Juan
dc.contributor.authorBultynck, Geert
dc.contributor.authorPonsaerts, Raf
dc.contributor.authorLeybaert, Luc
dc.contributor.authorSimon, Felipe
dc.contributor.authorSáez, Juan
dc.contributor.authorRetamal, Mauricio
dc.date.accessioned2017-05-25T15:03:43Z
dc.date.available2017-05-25T15:03:43Z
dc.date.issued2012
dc.descriptionCentro de Fisiología Celular e Integrativa
dc.description.abstractRecent 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.
dc.format.extent8
dc.identifier.citationFASEB J. 2012 Sep 26(9) 3649-57
dc.identifier.urihttp://hdl.handle.net/11447/1328
dc.identifier.urihttp://dx.doi.org/10.1096/fj.11-198416
dc.language.isoen_US
dc.publisherFederation of American Societies for Experimental Biology
dc.subjectAmygdala/physiology
dc.subjectAstrocytes/metabolism
dc.subjectConnexin 43/metabolism
dc.subjectFear
dc.subjectMemory
dc.subjectNeurotransmitter Agents/metabolism
dc.subjectRats
dc.titleRelease of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala
dc.typeArtículo

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