Project 454730

In dementia, brain cells that secrete an important chemical messenger named acetylcholine malfunction. Acetylcholine is a well-known neurotransmitter that regulates many brain processes, including attention, learning and memory. Part of acetylcholine action in the brain depends on a type of support cell called astrocyte, however we know little about the acetylcholine-astrocyte connection. I propose to investigate how loss of acetylcholine affects brain cells and impairs several cognitive processes. In addition, I aim to improve acetylcholine communication with astrocytes in an Alzheimer's disease (AD) mouse model and determine whether this approach prevents/ameliorates cognitive deficits. For this, I will use a state-of-the-art technique to mimic how acetylcholine controls astrocytes and test mice that have been submitted to this treatment to behavioral tasks that assess memory. Behavioral tasks will be done in automated touchscreens, similar to iPADs, and paradigms used will be comparable to those applied in humans, which facilitates translation. I will also determine how acetylcholine modulation of astrocytes affects brain chemicals while mice are performing behavioral tests. For that, I will use highly sensitive sensors that shine light upon the presence of specific brain chemicals. This procedure will allow me to determine how brain chemicals change when mice are doing specific activities during the behavioral test (touching the screen, collecting reward) or after an outcome (correct answer, wrong answer). These experiments can establish how acetylcholine modulation of astrocyte activity influences brain functions and lead to new directions to prevent memory deficits and improve cognitive function in neurodegenerative diseases, including Alzheimer's disease.