Release of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala.
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.
Laboratorio de Neurobiologia, Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas and Facultad de Medicina, Universidad Andres Bello, Santiago, Chile. jstehberg@unab.cl
Jimmy
J
Stehberg
Rodrigo
R
Moraga-Amaro
Christian
C
Salazar
Alvaro
A
Becerra
Cesar
C
Echeverría
Juan A
JA
Orellana
Geert
G
Bultynck
Raf
R
Ponsaerts
Luc
L
Leybaert
Felipe
F
Simon
Juan C
JC
Sáez
Mauricio A
MA
Retamal
D000679:Amygdala / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D018031:Connexin 43 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005239:Fear; D007150:Immunohistochemistry; D008568:Memory; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018031:Connexin 43; D018377:Neurotransmitter Agents