title: Amyloid-β induces synaptic dysfunction through G protein-gated inwardly rectifying potassium channels in the fimbria-CA3 hippocampal synapse.
abstract: Last evidences suggest that, in Alzheimer's disease (AD) early stage, Amyloid-β (Aβ) peptide induces an imbalance between excitatory and inhibitory neurotransmission systems resulting in the functional impairment of neural networks. Such alterations are particularly important in the septohippocampal system where learning and memory processes take place depending on accurate oscillatory activity tuned at fimbria-CA3 synapse. Here, the acute effects of Aβ on CA3 pyramidal neurons and their synaptic activation from septal part of the fimbria were studied in rats. A triphasic postsynaptic response defined by an excitatory potential (EPSP) followed by both early and late inhibitory potentials (IPSP) was evoked. The EPSP was glutamatergic acting on ionotropic receptors. The early IPSP was blocked by GABAA antagonists whereas the late IPSP was removed by GABAB antagonists. Aβ perfusion induced recorded cells to depolarize, increase their input resistance and decrease the late IPSP. Aβ action mechanism was localized at postsynaptic level and most likely linked to GABAB-related ion channels conductance decrease. In addition, it was found that the specific pharmacological modulation of the GABAB receptor effector, G-protein-coupled inward rectifier potassium (GirK) channels, mimicked all Aβ effects previously described. Thus, our findings suggest that Aβ altering GirK channels conductance in CA3 pyramidal neurons might have a key role in the septohippocampal activity dysfunction observed in AD.
authors.affiliation: Laboratorio Neurofisiología y Comportamiento, Facultad de Medicina de Ciudad Real, Universidad de Castilla-La Mancha Ciudad Real, Spain ; Department of Fisiología y Farmacología, Universidad de Salamanca Salamanca, Spain.
authors.forename: Mauricio O
authors.initials: MO
authors.lastname: Nava-Mesa
authors.forename: Lydia
authors.initials: L
authors.lastname: Jiménez-Díaz
authors.forename: Javier
authors.initials: J
authors.lastname: Yajeya
authors.forename: Juan D
authors.initials: JD
authors.lastname: Navarro-Lopez
keywords: Alzheimer's disease; GABAB; GirK channels; amyloid-β25–35 peptide; brain slices; fimbria-CA3 synapse; intracellular recordings; septohippocampal system
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