Browsing by Author "Fuenzalida, Marco"

Now showing 1 - 6 of 6
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    Coordinated prefrontal-hippocampal activity and navigation strategy-related prefrontal firing during spatial memory formation
    (2018) Negron-Oyarzo, Ignacio; Espinosa, Nelson; Aguilar, Marcelo; Fuenzalida, Marco; Aboitiz, Francisco; Fuentealba, Pablo
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    In vivo Activation of Wnt Signaling Pathway Enhances Cognitive Function of Adult Mice and Reverses Cognitive Deficits in an Alzheimer's Disease Model
    (2014) Vargas, Jessica Y.; Fuenzalida, Marco; Inestrosa, Nibaldo C.
    The role of the Wnt signaling pathway during synaptic development has been well established. In the adult brain, different components of Wnt signaling are expressed, but little is known about its role in mature synapses. Emerging in vitro studies have implicated Wnt signaling in synaptic plasticity. Furthermore, activation of Wnt signaling has shown to protect against amyloid-beta-induced synaptic impairment. The present study provides the first evidence that in vivo activation of Wnt signaling improves episodic memory, increases excitatory synaptic transmission, and enhances long-term potentiation in adult wild-type mice. Moreover, the activation of Wnt signaling also rescues memory loss and improves synaptic dysfunction in APP/PS1-transgenic mice that model the amyloid pathology of Alzheimer's diseases. These findings indicate that Wnt signaling modulates cognitive function in the adult brain and could be a novel promising target for Alzheimer's disease therapy.
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    Ketamine-Treatment During Late Adolescence Impairs Inhibitory Synaptic Transmission in the Prefrontal Cortex and Working Memory in Adult Rats
    (2019) Angel Perez, Miguel; Morales, Camila; Santander, Odra; Garcia, Francisca; Gomez, Isabel; Penaloza-Sancho, Valentin; Fuentealba, Pablo; Dagnino-Subiabre, Alexies; Moya, Pablo R.; Fuenzalida, Marco
    Schizophrenia (SZ) is associated with changes in the structure and function of several brain areas. Several findings suggest that these impairments are related to a dysfunction in gamma-aminobutyric acid (GABA) neurotransmission in brain areas such as the medial prefrontal cortex (mPFC), the hippocampus (HPC) and the primary auditory cortex (A1); however, it is still unclear how the GABAergic system is disrupted in these brain areas. Here, we examined the effect of ketamine (Ket) administration during late adolescence in rats on inhibition in the mPFC-, ventral HPC (vHPC), and A1. We observe that Ket treatment reduced the expression of the calcium-binding protein parvalbumin (PV) and the GABA-producing enzyme glutamic acid decarboxylase 67 (GAD67) as well as decreased inhibitory synaptic efficacy in the mPFC. In addition, Ket- treated rats performed worse in executive tasks that depend on the integrity and proper functioning of the mPFC. Conversely, we do not find such changes in vHPC or A1. Together, our results provide strong experimental support for the hypothesis that during adolescence, the function of the mPFC is more susceptible than that of HPC or A1 to NMDAR hypofunction, showing apparent structure specificity. Thus, the impairment of inhibitory circuitry in mPFC could be a convergent primary site of SZ-like behavior during the adulthood.
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    WASP-1, a canonical Wnt signaling potentiator, rescues hippocampal synaptic impairments induced by Aβ oligomers
    (2015) Vargas, Jessica Y.; Ahumada, Juan; Arrázola, Macarena S.; Fuenzalida, Marco; Inestrosa Cantín, Nibaldo
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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.
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    Wnt-5a Signaling Mediates Metaplasticity at Hippocampal CA3-CA1 Synapses in Mice
    (2024) Parodi, Jorge; Mira, Rodrigo G.; Fuenzalida, Marco; Cerpa, Waldo; Serrano, Felipe G.; Tapia-Rojas, Cheril; Martinez-Torres, Ataulfo; Inestrosa, Nibaldo C.
    Wnt signaling plays a role in synaptic plasticity, but the specific cellular events and molecular components involved in Wnt signaling-mediated synaptic plasticity are not well defined. Here, we report a change in the threshold required to induce synaptic plasticity that facilitates the induction of long-term potentiation (LTP) and inhibits the induction of long-term depression (LTD) during brief exposure to the noncanonical ligand Wnt-5a. Both effects are related to the metaplastic switch of hippocampal CA3-CA1 synaptic transmission, a complex mechanism underlying the regulation of the threshold required to induce synaptic plasticity and of synaptic efficacy. We observed an early increase in the amplitude of field excitatory postsynaptic potentials (fEPSPs) that persisted over time, including after washout. The first phase involves an increase in the fEPSP amplitude that is required to trigger a spontaneous second phase that depends on Jun N-terminal kinase (JNK) and N-methyl D-aspartate receptor (NMDAR) activity. These changes are prevented by treatment with secreted frizzled-related protein 2 (sFRP-2), an endogenous antagonist of Wnt ligands. Here, we demonstrate the contribution of Wnt-5a signaling to a process associated with metaplasticity at CA3-CA1 synapses that favors LTP over LTD.