Browsing by Author "Bonansco, Christian"

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    Astroglial Ca2+-dependent hyperexcitability requires P2Y 1 purinergic receptors and pannexin-1 channel activation in a chronic model of epilepsy
    (2018) Wellmann, Mario; Alvarez Ferradas, Carla; Maturana, Carola J.; Sáez, Juan Carlos; Bonansco, Christian
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    How Are Synapses Born? A Functional and Molecular View of the Role of the Wnt Signaling Pathway
    (2022) Bonansco, Christian; Cerpa Nebott, Waldo; Inestrosa, Nibaldo C.
    Synaptic transmission is a dynamic process that requires precise regulation. Early in life, we must be able to forge appropriate connections (add and remove) to control our behavior. Neurons must recognize appropriate targets, and external soluble factors that activate specific signaling cascades provide the regulation needed to achieve this goal. Wnt signaling has been implicated in several forms of synaptic plasticity, including functional and structural changes associated with brain development. The analysis of synapses from an electrophysiological perspective allows us to characterize the functional role of cellular signaling pathways involved in brain development. The application of quantal theory to principles of developmental plasticity offers the possibility of dissecting the function of structural changes associated with the birth of new synapses as well as the maturation of immature silent synapses. Here, we focus on electrophysiological and molecular evidence that the Wnt signaling pathway regulates glutamatergic synaptic transmission, specifically N-methyl-d-aspartate receptors (NMDARs), to control the birth of new synapses. We also focus on the role of Wnts in the conversion of silent synapses into functional synapses.
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    Wnt-5a induces the conversion of silent to functional synapses in the hippocampus
    (2022) Alvarez-Ferradas, Carla; Wellmann, Mario; Morales, Koyam; Fuenzalida, Marco; Cerpa, Waldo; Inestrosa, Nibaldo C.; Bonansco, Christian
    Synapse unsilencing is an essential mechanism for experience-dependent plasticity. Here, we showed that the application of the ligand Wnt-5a converts glutamatergic silent synapses into functional ones by increasing both alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) currents (I-AMPA and I-NMDA, respectively). These effects were mimicked by the hexapeptide Foxy-5 and inhibited by secreted frizzled-related protein sFRP-2. I-NMDA potentiation was produced by increased synaptic potency, followed by an increase in the probability of release (Pr), even in the presence of 7-nitro-2,3-dioxo-1,4-dihydroquinoxaline-6-carbonitrile (CNQX). At a longer time of Wnt-5a exposure, the Pr increments were higher in I-NMDA than in I-AMPA. In the presence of NMDAR inhibitors, Wnt-5a-induced conversion was fully inhibited in 69.0% of silent synapses, whereas in the remaining synapses were converted into functional one. Our study findings showed that the Wnt-5a-activated pathway triggers AMPAR insertion into mammalian glutamatergic synapses, unsilencing non-functional synapses and promoting the formation of nascent synapses during the early postnatal development of the brain circuits.