Affiliated with Université Laval & CERVO Research Centre
Ph.D. (2016-2022) - Imbalance of inhibitory control and excitatory drive associated with cognitive deficits in Alzheimer’s disease and aging
Alzheimer disease (AD) has been associated with an abnormal brain activity common to other brain disorders. This aberrant brain activity appears to arise from disrupted GABAA-mediated inhibitory signaling near amyloid-β plaques, leading to neocortical and hippocampal hyperactivity, impaired network oscillations and under certain conditions to epileptiform activity and seizures both in mice and humans. Several hypotheses have been emerged on the origin of GABAergic neurotransmission disruption, but impaired chloride homeostasis arises as a promising mechanism. Hence, the objective of this project is to test whether several AD-related symptoms can be prevented or attenuated by restoring chloride extrusion and GABAA-mediated inhibition in AD.
Follow the link bellow, if you wish to have a brief overview of this project:
Disruption of inhibition in Alzheimer's disease
Aging is the most impactful risk factor for neurodegeneration. However, given that in elderly populations neurodegeneration is common and that in very old individuals cognitive decline is prominent, one could argue that neurodegenerative disorders are a manifestation of accelerated aging. Yet, the mechanisms underlying age-related cognitive decline and senile dementia are distinct to the mechanisms inducing Alzheimer's disease (the most common neurodegenerative disorder). Thus, this project aims to understand which are the specific changes in synaptic transmission associated with aging-related neurodegeneration and cognitive decline.
Evoked hippocampal hyperactivity in transgenic mice carrying AD-linked mutations has been shown to increase significantly amyloid-β deposition. In addition, neuronal hyperactivity seems to contribute to neural circuit disruption in early stages of AD. However, it still remains unknown which are the overall effects of this neuronal hyperactivity in cellular proteostasis, and whether any of these proteome alterations could further facilitate neuronal hyperexcitability and the over-production of amyloid-β in AD.
In vivo and in vitro optogenetics; in vivo electrophysiology; in vivo and ex vivo cellular calcium and chloride imaging; cognitive and social behavioral measurements; immunoblots; immunohistochemistry; single neuron morphology reconstruction
