Affiliated with Université Laval & CERVO Research Centre

Iason Keramidis

Ph.D. Student

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 proper balance between synaptic excitation and inhibition (E/I ratio) is pivotal for normal brain functioning and subtle disruptions of this balance likely underlies behavioral and cognitive deficits in patients. Such a disruption has been reported in multiple animal models of AD, already in the pre-symptomatic phase. 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 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 by restoring GABAergic inhibition and subsequently the normal excitation/inhibition ratio in the prefrontal cortex we can prevent or attenuate the social and cognitive impairments in an animal model of Alzheimer’s disease.

 

Techniques:

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