BME PhD Proposal Presentation 

Date: Monday, September 16th, 2019

Time: 1:00 pm

Location: HSRB E160

Committee Members: 

Annabelle Singer, PhD (Advisor) 

James Lah, MD, PhD 

Robert Liu, PhD

Joseph Manns, PhD

Garrett Stanley, PhD 

Title: Bringing gamma back: the effects of non-invasive gamma stimulation on neural activity 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. The hippocampus, an area of the brain crucial for spatial learning and memory, is affected early in the course of AD. Previously, we discovered that acute exposure to 40 Hz auditory and light flicker stimulation drives gamma frequency neural activity in the hippocampus. Furthermore, extending gamma stimulation exposure from acute presentations to multiple days of stimulation periods reduces amyloid beta levels, recruits microglia to engulf amyloid beta, and improves performance in spatial memory tasks in a mouse model of AD. However, it is unknown how prolonged manipulation of hippocampal activity impacts deficits in neural activity crucial for learning and memory. Thus, the goal of this proposal is to study the functional effects of gamma frequency sensory stimulation on deficits in neural connections and neural codes essential for learning and memory in the hippocampus of a mouse model of AD. Aim 1 will establish how prolonged gamma stimulation affects deficient inhibition of excitatory pyramidal cells in the hippocampus. Aim 2 will examine the effects of prolonged gamma stimulation on deficits in patterns of hippocampal activity that are important for learning and memory. To achieve these aims, local field potentials and spiking activity will be recorded from many single neurons in head-fixed mice as they navigate through a virtual reality (VR) environment. This innovative approach will allow neural activity to be recorded from awake, behaving mice, the primary animal model of disease, with the high temporal resolution and large number of cells needed to study precise neural activity in the hippocampus. The proposed work has the potential to result in a non-invasive method to rescue neural activity deficits, carrying promising translational applications to Alzheimer’s disease, as well as other neurological diseases with altered oscillatory neural activity.