Project aim: Investigating GABA-dependent neuronal inhibition in cognitive and behavioral deficits associated with Alzheimer’s disease
Alzheimer disease (AD) is associated with an abnormal brain activity common to other brain disorders such as epilepsy, Down syndrome, autism and frontotemporal dementia. A growing number of evidence suggest that an imbalance between synaptic excitation and inhibition (E/I ratio) may result into an abnormal neuronal network functioning underlying the behavioral and cognitive deficits observed in those diseases. Such a disruption has been reported as early as the pre-symptomatic phase in animal models of Alzheimer’s disease. Specifically, transient seizure-like network hyperactivity has been described in the prefrontal cortex and the hippocampus of patients and in animal models of AD with the hyperactive neurons being observed near amyloid plaques in vivo. Several hypotheses have emerged on the origin of this hyperexcitability. Among these, recent findings implicate amyloid-β-mediated disruption of GABAA-mediated transmission, potentially underlying neuronal hyperactivity observed in AD.
The objective of this project is to test whether the cognitive and behavioral impairments observed in an animal model of Alzheimer’s disease can be prevented or attenuated by restoring GABAergic inhibition and subsequently the normal excitation/inhibition ratio in the prefrontal cortex.
In vivo optogenetics; in vivo wireless electrophysiology; in-vivo micro-optrode recordings; cognitive and social behavioral measurments; immunoblots; immunostainings; confocal microscopy; Luficer yellow injections; neurons morphology reconstruction