Amyloid-? induces synaptic dysfunction through G protein-gated inwardly rectifying potassium channels in the fimbria-CA3 hippocampal synapse
Título de la revista
Nava Mesa, Mauricio Orlando
Navarro-Lopez, Juan D.
ISSN de la revista
Título del volumen
Last evidences suggest that, in Alzheimer's disease (AD) early stage, Amyloid-? (A?) 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 A? 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. A? perfusion induced recorded cells to depolarize, increase their input resistance and decrease the late IPSP. A? 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 A? effects previously described.
Septohippocampal system , Fimbria-CA3 synapse , Amyloid-?25–35 peptide , GABAB , GirK channels , Alzheimer's disease , Brain slices , Intracellular recordings