Title: Release of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala
Abstract: The FASEB JournalVolume 26, Issue 9 p. 3649-3657 Research CommunicationFree to Read Release of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala Jimmy Stehberg, Corresponding Author Jimmy Stehberg [email protected] Laboratorio de Neurobiologia, Universidad Andres Bello, Santiago, Chile Centro de Investigaciones Biomédicas, Universidad Andres Bello, Santiago, ChileCorrespondence: Laboratorio de Neurobiologia, Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas and Facultad de Medicina, Universidad Andres Bello, Santiago, Chile. E-mail: [email protected]Search for more papers by this authorRodrigo Moraga-Amaro, Rodrigo Moraga-Amaro Laboratorio de Neurobiologia, Universidad Andres Bello, Santiago, ChileSearch for more papers by this authorChristian Salazar, Christian Salazar Laboratorio de Neurobiologia, Universidad Andres Bello, Santiago, ChileSearch for more papers by this authorAlvaro Becerra, Alvaro Becerra Laboratorio de Fisiopatologia Integrativa, Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas and Facultad de Medicina, Universidad Andres Bello, Santiago, ChileSearch for more papers by this authorCesar Echeverría, Cesar Echeverría Laboratorio de Fisiopatologia Integrativa, Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas and Facultad de Medicina, Universidad Andres Bello, Santiago, ChileSearch for more papers by this authorJuan A. Orellana, Juan A. Orellana Departamento de Neurología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, ChileSearch for more papers by this authorGeert Bultynck, Geert Bultynck Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, Katholieke Universiteit Leuven, Leuven, BelgiumSearch for more papers by this authorRaf Ponsaerts, Raf Ponsaerts Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, Katholieke Universiteit Leuven, Leuven, BelgiumSearch for more papers by this authorLuc Leybaert, Luc Leybaert Department of Basic Medical Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, BelgiumSearch for more papers by this authorFelipe Simon, Felipe Simon Laboratorio de Fisiopatologia Integrativa, Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas and Facultad de Medicina, Universidad Andres Bello, Santiago, Chile Millennium Institute on Immunology and Immunotherapy, Santiago, ChileSearch for more papers by this authorJuan C. Sáez, Juan C. Sáez Departamento de Fisiología, Pontificia Universidad Católica de Chile, Santiago, Chile Instituto Milenio, Centro Interdiciplinario de Neurociencias de Valparaíso, Valparaíso, ChileSearch for more papers by this authorMauricio A. Retamal, Mauricio A. Retamal Departamento de Fisiología, Facultad de Medicina, Clínica Alemana-Universidad del Desarrollo, Santiago, ChileSearch for more papers by this author Jimmy Stehberg, Corresponding Author Jimmy Stehberg [email protected] Laboratorio de Neurobiologia, Universidad Andres Bello, Santiago, Chile Centro de Investigaciones Biomédicas, Universidad Andres Bello, Santiago, ChileCorrespondence: Laboratorio de Neurobiologia, Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas and Facultad de Medicina, Universidad Andres Bello, Santiago, Chile. E-mail: [email protected]Search for more papers by this authorRodrigo Moraga-Amaro, Rodrigo Moraga-Amaro Laboratorio de Neurobiologia, Universidad Andres Bello, Santiago, ChileSearch for more papers by this authorChristian Salazar, Christian Salazar Laboratorio de Neurobiologia, Universidad Andres Bello, Santiago, ChileSearch for more papers by this authorAlvaro Becerra, Alvaro Becerra Laboratorio de Fisiopatologia Integrativa, Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas and Facultad de Medicina, Universidad Andres Bello, Santiago, ChileSearch for more papers by this authorCesar Echeverría, Cesar Echeverría Laboratorio de Fisiopatologia Integrativa, Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas and Facultad de Medicina, Universidad Andres Bello, Santiago, ChileSearch for more papers by this authorJuan A. Orellana, Juan A. Orellana Departamento de Neurología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, ChileSearch for more papers by this authorGeert Bultynck, Geert Bultynck Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, Katholieke Universiteit Leuven, Leuven, BelgiumSearch for more papers by this authorRaf Ponsaerts, Raf Ponsaerts Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, Katholieke Universiteit Leuven, Leuven, BelgiumSearch for more papers by this authorLuc Leybaert, Luc Leybaert Department of Basic Medical Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, BelgiumSearch for more papers by this authorFelipe Simon, Felipe Simon Laboratorio de Fisiopatologia Integrativa, Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas and Facultad de Medicina, Universidad Andres Bello, Santiago, Chile Millennium Institute on Immunology and Immunotherapy, Santiago, ChileSearch for more papers by this authorJuan C. Sáez, Juan C. Sáez Departamento de Fisiología, Pontificia Universidad Católica de Chile, Santiago, Chile Instituto Milenio, Centro Interdiciplinario de Neurociencias de Valparaíso, Valparaíso, ChileSearch for more papers by this authorMauricio A. Retamal, Mauricio A. Retamal Departamento de Fisiología, Facultad de Medicina, Clínica Alemana-Universidad del Desarrollo, Santiago, ChileSearch for more papers by this author First published: 04 June 2012 https://doi.org/10.1096/fj.11-198416Citations: 20Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL 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.—Stehberg, J., Moraga-Amaro, R., Salazar, C., Becerra, A., Echeverría, C., Orellana, J. A., Bultynck, G., Ponsaerts, R., Leybaert, L., Simon, F., Sáez, J. C., Retamal, M. A. Release of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala. FASEB J. 26, 3649–3657 (2012). www.fasebj.org Citing Literature Volume26, Issue9September 2012Pages 3649-3657 RelatedInformation