Browsing by Author "Stehberg, Jimmy"

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    Astroglial gliotransmitters released via Cx43 hemichannels regulate NMDAR-dependent transmission and short-term fear memory in the basolateral amygdala
    (2022) Linsambarth, Sergio; Carvajal Cachaña, Francisco Javier; Moraga Amaro, Rodrigo; Mendez, Luis; Tamburini, Giovanni; Jimenez, Ivanka; Antonio Verdugo, Daniel; Gomez, Gonzalo, I; Jury, Nur; Martinez, Pablo; van Zundert, Brigitte; Varela Nallar, Lorena; Retamal, Mauricio A.; Martin, Claire; Altenberg, Guillermo A.; Fiori, Mariana C.; Cerpa Nebott, Waldo Francisco; Orellana Roca, Juan Andrés; Stehberg, Jimmy
    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.
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    Deep Transcranial Magnetic Stimulation for the Treatment of Negative Symptoms in Schizophrenia Beyond an Antidepressant Effect
    (2019) Linsambarth, Sergio; Jeria Durán, Álvaro; Avirame, Keren; Doron, Todder; Riquelme, Raúl; Stehberg, Jimmy
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    GABAergic Regulation of Astroglial Gliotransmission through Cx43 Hemichannels
    (2022) Jimenez-Dinamarca, Ivanka; Reyes-Lizana, Rachel; Lemunao-Inostroza, Yordan; Cardenas, Kevin; Castro-Lazo, Raimundo; Peña, Francisca; Lucero, Claudia M.; Prieto Villalobos, Juan Carlos; Retamal, Mauricio Antonio; Orellana Roca, Juan Andrés; Stehberg, Jimmy
    Gamma-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain. It is produced by interneurons and recycled by astrocytes. In neurons, GABA activates the influx of Cl- via the GABA(A) receptor or efflux or K+ via the GABA(B) receptor, inducing hyperpolarization and synaptic inhibition. In astrocytes, the activation of both GABA(A) and GABA(B) receptors induces an increase in intracellular Ca2+ and the release of glutamate and ATP. Connexin 43 (Cx43) hemichannels are among the main Ca2+-dependent cellular mechanisms for the astroglial release of glutamate and ATP. However, no study has evaluated the effect of GABA on astroglial Cx43 hemichannel activity and Cx43 hemichannel-mediated gliotransmission. Here we assessed the effects of GABA on Cx43 hemichannel activity in DI NCT1 rat astrocytes and hippocampal brain slices. We found that GABA induces a Ca2+-dependent increase in Cx43 hemichannel activity in astrocytes mediated by the GABA(A) receptor, as it was blunted by the GABA(A) receptor antagonist bicuculline but unaffected by GABA(B) receptor antagonist CGP55845. Moreover, GABA induced the Cx43 hemichannel-dependent release of glutamate and ATP, which was also prevented by bicuculline, but unaffected by CGP. Gliotransmission in response to GABA was also unaffected by pannexin 1 channel blockade. These results are discussed in terms of the possible role of astroglial Cx43 hemichannel-mediated glutamate and ATP release in regulating the excitatory/inhibitory balance in the brain and their possible contribution to psychiatric disorders.
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    Role of Astroglial Hemichannels and Pannexons in Memory and Neurodegenerative Diseases
    (2016) Orellana Roca, Juan Andrés; Retamal, Mauricio A.; Moraga Amaro, Rodrigo; Stehberg, Jimmy