Impairments of Synaptic Plasticity Induction Threshold and Network Oscillatory Activity in the Hippocampus Underlie Memory Deficits in a Non-Transgenic Mouse Model of Amyloidosis
Jennifer Mayordomo-Cava,
Guillermo Iborra-Lázaro,
Souhail Djebari,
Sara Temprano-Carazo,
Irene Sánchez-Rodríguez,
Danko Jeremic,
Agnès Gruart,
José María Delgado-García,
Lydia Jiménez-Díaz,
Juan D. Navarro-López
Affiliations
Jennifer Mayordomo-Cava
Neurophysiology and Behavioral Lab, Centro Regional de Investigaciones Biomédicas, School of Medicine of Ciudad Real, University of Castilla-La Mancha, 13071 Ciudad Real, Spain
Guillermo Iborra-Lázaro
Neurophysiology and Behavioral Lab, Centro Regional de Investigaciones Biomédicas, School of Medicine of Ciudad Real, University of Castilla-La Mancha, 13071 Ciudad Real, Spain
Souhail Djebari
Neurophysiology and Behavioral Lab, Centro Regional de Investigaciones Biomédicas, School of Medicine of Ciudad Real, University of Castilla-La Mancha, 13071 Ciudad Real, Spain
Sara Temprano-Carazo
Neurophysiology and Behavioral Lab, Centro Regional de Investigaciones Biomédicas, School of Medicine of Ciudad Real, University of Castilla-La Mancha, 13071 Ciudad Real, Spain
Irene Sánchez-Rodríguez
Neurophysiology and Behavioral Lab, Centro Regional de Investigaciones Biomédicas, School of Medicine of Ciudad Real, University of Castilla-La Mancha, 13071 Ciudad Real, Spain
Danko Jeremic
Neurophysiology and Behavioral Lab, Centro Regional de Investigaciones Biomédicas, School of Medicine of Ciudad Real, University of Castilla-La Mancha, 13071 Ciudad Real, Spain
Agnès Gruart
Division of Neurosciences, Pablo de Olavide University, 41013 Seville, Spain
José María Delgado-García
Division of Neurosciences, Pablo de Olavide University, 41013 Seville, Spain
Lydia Jiménez-Díaz
Neurophysiology and Behavioral Lab, Centro Regional de Investigaciones Biomédicas, School of Medicine of Ciudad Real, University of Castilla-La Mancha, 13071 Ciudad Real, Spain
Juan D. Navarro-López
Neurophysiology and Behavioral Lab, Centro Regional de Investigaciones Biomédicas, School of Medicine of Ciudad Real, University of Castilla-La Mancha, 13071 Ciudad Real, Spain
In early Alzheimer disease (AD) models synaptic failures and upstreaming aberrant patterns of network synchronous activity result in hippocampal-dependent memory deficits. In such initial stage, soluble forms of Amyloid-β (Aβ) peptides have been shown to play a causal role. Among different Aβ species, Aβ25–35 has been identified as the biologically active fragment, as induces major neuropathological signs related to early AD stages. Consequently, it has been extensively used to acutely explore the pathophysiological events related with neuronal dysfunction induced by soluble Aβ forms. However, the synaptic mechanisms underlying its toxic effects on hippocampal-dependent memory remain unresolved. Here, in an in vivo model of amyloidosis generated by intracerebroventricular injections of Aβ25–35 we studied the synaptic dysfunction mechanisms underlying hippocampal cognitive deficits. At the synaptic level, long-term potentiation (LTP) of synaptic excitation and inhibition was induced in CA1 region by high frequency simulation (HFS) applied to Schaffer collaterals. Aβ25–35 was found to alter metaplastic mechanisms of plasticity, facilitating long-term depression (LTD) of both types of LTP. In addition, aberrant synchronization of hippocampal network activity was found while at the behavioral level, deficits in hippocampal-dependent habituation and recognition memories emerged. Together, our results provide a substrate for synaptic disruption mechanism underlying hippocampal cognitive deficits present in Aβ25–35 amyloidosis model.