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How disruption of the excitation/inhibition (E/I) ratio in the hippocampus of young transgenic mouse models of Alzheimer's disease affects synaptic plasticity and memory processes in adults

Objectifs

Investigate the cellular mechanisms involved in the disruption of E/I ratio in a young mouse model of Alzheimer disease and how these perturbations affect glutamatergic synaptic transmission in the hippocampus of adults.
 

Résumé

Neurons and circuits coordinate their excitatory and inhibitory inputs to establish and maintain a constant Excitatory/Inhibitory (E/I) ratio that is thought to be essential for circuit function and stability. Experimental evidence supports the idea that balanced excitation and inhibition within neural circuits facilitates their function, and that failure to maintain E/I balance underlies circuit dysfunction seen in many neurological diseases. The hippocampus is one of the first brain regions to be affected in Alzheimer’s disease and is important for forming memories and emotions. We showed that E/I ratio is disrupted in the hippocampus of young APP/PS1 mice, a mouse model of Alzheimer disease. We reveal that these perturbations require the expression of APP, a transmembrane protein essential for synapses to form and work correctly. The main objective of this project will consist to investigate how these perturbations in young animals can affect neuronal network function in the hippocampus of adults.
 

Méthodes

We will use different electrophysiological techniques to measure basal glutamatergic and GABAergic transmission as well as synaptic plasticity phenomenon (Long term potentiation) in the hippocampus. Morphology of dendritic spine will be assessed using confocal microscopy. By targeting the mechanism involved in E/I disruption with pharmacological treatment in young animal, we may stop the propagation of the disease at latter stage.
 

Références

 

Domaines d'expertise requis

Electrophysiology, Confocal microscopy, Cellular Biology.
 

Contacts

Fabien Lanté MCF
Email : fabien.lante@univ-grenoble-alpes.fr
Phone : +33 4 56 52 06 39

Téléchargement(s)

Mise à jour le 8 juillet 2022

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