PMID- 35061296
OWN - NLM
STAT- MEDLINE
DCOM- 20220214
LR  - 20220214
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 36
IP  - 2
DP  - 2022 Feb
TI  - Astroglial gliotransmitters released via Cx43 hemichannels regulate 
      NMDAR-dependent transmission and short-term fear memory in the basolateral 
      amygdala.
PG  - e22134
LID - 10.1096/fj.202100798RR [doi]
AB  - Astrocytes release gliotransmitters via connexin 43 (Cx43) hemichannels into 
      neighboring synapses, which can modulate synaptic activity and are necessary for 
      fear memory consolidation. However, the gliotransmitters released, and their 
      mechanisms of action remain elusive. Here, we report that fear conditioning 
      training elevated Cx43 hemichannel activity in astrocytes from the basolateral 
      amygdala (BLA). The selective blockade of Cx43 hemichannels by microinfusion of 
      TAT-Cx43L2 peptide into the BLA induced memory deficits 1 and 24 h after 
      training, without affecting learning. The memory impairments were prevented by 
      the co-injection of glutamate and D-serine, but not by the injection of either 
      alone, suggesting a role for NMDA receptors (NMDAR). The incubation with 
      TAT-Cx43L2 decreased NMDAR-mediated currents in BLA slices, effect that was also 
      prevented by the addition of glutamate and D-serine. NMDARs in primary neuronal 
      cultures were unaffected by TAT-Cx43L2, ruling out direct effects of the peptide 
      on NMDARs. Finally, we show that D-serine permeates through purified 
      Cx43 hemichannels reconstituted in liposomes. We propose that the release of 
      glutamate and D-serine from astrocytes through Cx43 hemichannels is necessary for 
      the activation of post-synaptic NMDARs during training, to allow for the 
      formation of short-term and subsequent long-term memory, but not for learning per 
      se.
CI  - (c) 2022 Federation of American Societies for Experimental Biology.
FAU - Linsambarth, Sergio
AU  - Linsambarth S
AD  - Laboratorio de Neurobiologia, Instituto de Ciencias Biomedicas, Facultad de 
      Medicina y Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, 
      Chile.
FAU - Carvajal, Francisco J
AU  - Carvajal FJ
AD  - Laboratorio de Funcion y Patologia Neuronal, Departamento de Biologia Celular y 
      Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de 
      Chile, Santiago, Chile.
FAU - Moraga-Amaro, Rodrigo
AU  - Moraga-Amaro R
AD  - Laboratorio de Neurobiologia, Instituto de Ciencias Biomedicas, Facultad de 
      Medicina y Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, 
      Chile.
FAU - Mendez, Luis
AU  - Mendez L
AD  - Laboratorio de Neurobiologia, Instituto de Ciencias Biomedicas, Facultad de 
      Medicina y Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, 
      Chile.
FAU - Tamburini, Giovanni
AU  - Tamburini G
AD  - Laboratorio de Neurobiologia, Instituto de Ciencias Biomedicas, Facultad de 
      Medicina y Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, 
      Chile.
FAU - Jimenez, Ivanka
AU  - Jimenez I
AD  - Laboratorio de Neurobiologia, Instituto de Ciencias Biomedicas, Facultad de 
      Medicina y Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, 
      Chile.
FAU - Verdugo, Daniel Antonio
AU  - Verdugo DA
AD  - Laboratorio de Neurobiologia, Instituto de Ciencias Biomedicas, Facultad de 
      Medicina y Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, 
      Chile.
FAU - Gomez, Gonzalo I
AU  - Gomez GI
AD  - Instituto de Ciencias Biomedicas, Facultad de Ciencias de la Salud, Universidad 
      Autonoma de Chile, Santiago, Chile.
FAU - Jury, Nur
AU  - Jury N
AD  - Instituto de Ciencias Biomedicas, Facultad de Medicina y Facultad de Ciencias de 
      la Vida, Universidad Andres Bello, Santiago, Chile.
FAU - Martinez, Pablo
AU  - Martinez P
AD  - Instituto de Ciencias Biomedicas, Facultad de Medicina y Facultad de Ciencias de 
      la Vida, Universidad Andres Bello, Santiago, Chile.
FAU - van Zundert, Brigitte
AU  - van Zundert B
AD  - Instituto de Ciencias Biomedicas, Facultad de Medicina y Facultad de Ciencias de 
      la Vida, Universidad Andres Bello, Santiago, Chile.
FAU - Varela-Nallar, Lorena
AU  - Varela-Nallar L
AD  - Instituto de Ciencias Biomedicas, Facultad de Medicina y Facultad de Ciencias de 
      la Vida, Universidad Andres Bello, Santiago, Chile.
FAU - Retamal, Mauricio A
AU  - Retamal MA
AD  - Centro de Fisiologia Celular e Integrativa. Facultad de Medicina, Clinica Alemana 
      Universidad del Desarrollo, Santiago, Chile.
FAU - Martin, Claire
AU  - Martin C
AD  - Unite de Biologie Fonctionnelle et Adaptative, Centre National la Recherche 
      Scientifique, Unite Mixte de Recherche 8251, Universite Paris Diderot, Sorbonne 
      Paris Cite, Paris, France.
FAU - Altenberg, Guillermo A
AU  - Altenberg GA
AD  - Department of Cell Physiology and Molecular Biophysics, Center for Membrane 
      Protein Research, Texas Tech University Health Sciences Center, Lubbock, Texas, 
      USA.
FAU - Fiori, Mariana C
AU  - Fiori MC
AD  - Department of Cell Physiology and Molecular Biophysics, Center for Membrane 
      Protein Research, Texas Tech University Health Sciences Center, Lubbock, Texas, 
      USA.
FAU - Cerpa, Waldo
AU  - Cerpa W
AD  - Laboratorio de Funcion y Patologia Neuronal, Departamento de Biologia Celular y 
      Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de 
      Chile, Santiago, Chile.
FAU - Orellana, Juan A
AU  - Orellana JA
AD  - Departamento de Neurologia, Escuela de Medicina, Pontificia Universidad Catolica 
      de Chile, Santiago, Chile.
FAU - Stehberg, Jimmy
AU  - Stehberg J
AD  - Laboratorio de Neurobiologia, Instituto de Ciencias Biomedicas, Facultad de 
      Medicina y Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, 
      Chile.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Connexin 43)
RN  - 0 (Gja1 protein, rat)
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 452VLY9402 (Serine)
SB  - IM
MH  - Animals
MH  - Astrocytes/*metabolism
MH  - Basolateral Nuclear Complex/*metabolism
MH  - Connexin 43/*metabolism
MH  - Fear/*physiology
MH  - Glutamic Acid/metabolism
MH  - Male
MH  - Memory, Short-Term/*physiology
MH  - Neurons/metabolism
MH  - Neurotransmitter Agents/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Serine/metabolism
OTO - NOTNLM
OT  - Connexin 43 hemichannels
OT  - Cx43
OT  - HCs
OT  - NMDA receptor
OT  - astrocytes
OT  - basolateral amygdala
OT  - d-serine
OT  - fear conditioning
OT  - memory
OT  - short-term memory
EDAT- 2022/01/22 06:00
MHDA- 2022/02/15 06:00
CRDT- 2022/01/21 12:18
PHST- 2021/12/16 00:00 [revised]
PHST- 2021/05/17 00:00 [received]
PHST- 2021/12/17 00:00 [accepted]
PHST- 2022/01/21 12:18 [entrez]
PHST- 2022/01/22 06:00 [pubmed]
PHST- 2022/02/15 06:00 [medline]
AID - 10.1096/fj.202100798RR [doi]
PST - ppublish
SO  - FASEB J. 2022 Feb;36(2):e22134. doi: 10.1096/fj.202100798RR.