Alzheimer?s disease is the most common neurodegenerative disorder and the leading cause of dementia in the elderly. Aberrant brain activity has become recognized as a key symptom in the prodromal period of Alzheimer?s disease, raising the possibility that brain stimulation in an early phase could prevent and restore cognitive decline in Alzheimer?s disease. In the current proposal, using mouse model of Alzheimer?s disease, we will investigate how the excitatory pyramidal neurons and inhibitory interneurons underlie the aberrant cortical activity and affect the progression of the disease.
In Aim 1, we will visualize the activity of pyramidal neurons and interneurons longitudinally using in vivo two-photon imaging, and examine how the activity changes during the formation of amyloid-beta plaques.
In Aim 2, we will manipulate the activity of pyramidal neurons and interneurons using optogenetics and examine how such manipulation will affect the aberrant activity and the progress of the disease. The findings in this project will provide pivotal information on how we can intervene and prevent cognitive decline, informing much- needed solutions for patients who suffer from Alzheimer?s disease.
Alzheimer?s disease is the most prevalent type of dementia, for which there is no effective treatment. Aberrant brain activity is increasingly viewed as one of the early symptoms of this disease, and could be a therapeutic entry point for an effective treatment. The proposed studies will uncover the circuit- level mechanisms of aberrant brain activity in Alzheimer?s disease using advanced optical techniques, and identify how we can modify the aberrant activity to prevent dementia.
