Abigail Paulson
BME PhD Defense Presentation
Date: 2023-05-04
Time: 11:00 AM
Location / Meeting Link: Dalney Street Building, room 180 / https://gatech.zoom.us/j/92436692515?pwd=a2NmTUI2UHd3SEFpTEc2RGwzOFFDdz09
Committee Members:
Annabelle Singer, PhD (advisor); James Lah, MD, PhD; Robert Liu, PhD; Joseph Manns, PhD; Garrett Stanley, PhD
Title: Rhythms to the rescue: the effects of non-invasive gamma stimulation on neural mechanisms of memory in a mouse model of Alzheimer’s disease
Abstract:
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder that is characterized by the accumulation of toxic proteins, aberrant neural activity, and deficits in spatial learning and memory. Recent work has shown that gamma frequency (40 Hz) light flicker stimulation recruits microglia to engulf pathogenic proteins that accumulate in visual cortex in AD. However, AD pathology affects many brain regions, including higher-order areas such as the hippocampus, an area of the brain crucial for spatial learning and memory. Thus, the goals of this dissertation were to adapt gamma frequency sensory stimulation to affect higher-order brain regions and to characterize the effects of this stimulation on neural circuits important for memory. First, we found that acute exposure to 40 Hz auditory and light flicker stimulation modulates neural activity in the hippocampus. Extending the duration of 40 Hz audio-visual flicker stimulation exposure to multiple days of regular stimulation reduces hippocampal amyloid-beta levels, recruits microglia to engulf amyloid-beta, and improves performance in spatial memory tasks in a mouse model of AD. We next investigated how prolonged exposure to 40 Hz flicker stimulation impacts neural communication and neural codes in the hippocampal circuit of 5XFAD mice. We found increased CA3-CA1 communication, a pathway implicated in memory retrieval and neural coding, and increased representation of future information during neural codes following 40 Hz flicker. This work shows that 40 Hz sensory flicker affects hippocampal communication important for memory retrieval, neural codes that support behavior, multiple aspects of AD-associated pathology, and improves cognition in the 5XFAD mouse model of Alzheimer’s disease. This non-invasive method to impact neural activity essential for cognitive function carries promising translational applications to Alzheimer’s disease, as well as other neurological diseases with altered rhythmic neural activity.