PhD Proposal by Mercedes Gonzalez
Mercedes Gonzalez BioE Ph.D. Proposal Presentation Time and Date: 9:00 am on Friday, December 9, 2022 Location: Suddath Room 1128, IBB Zoom link: Click here to join the meeting Advisors: Craig Forest, Ph.D. (Mechanical Engineering) Matthew Rowan, Ph.D. (Biological Sciences, Emory) Committee Members: Annabelle Singer, Ph.D. (Biomedical Engineering) Christopher Rozell , Ph.D. (Electrical and Computer Engineering) Bilal Haider, Ph.D. (Biomedical Engineering) Automated cellular electrophysiology to investigate the role of interneurons in Alzheimer's Disease Alzheimer's disease (AD) is the leading cause of dementia, affecting millions of people worldwide each year. AD is characterized by progressive decline in cognition and memory, often detected late in disease progression. A prevailing theory of AD has been that cognitive decline and memory loss is caused by progressive deposition of toxic amyloid and tau proteins. While significant efforts have been made to elucidate mechanisms behind these symptoms based on this idea, effective therapies remain elusive. An alternative hypothesis is that cognitive loss in early AD results from neuronal circuit dysregulation. In particular, parvalbumin-expressing (PV) interneurons are prone to changes in excitability in AD which contributes to circuit dysfunction. However, the spatiotemporal evolution of interneuron dysregulation throughout the brain is unclear. In addition, recent studies have found that 40 Hz optogenetic stimulation of PV-interneurons activates microglia and reduces amyloid beta load in aged AD mice, further supporting the idea that interneuron dysregulation plays a key role in AD progression. They also found that non-invasive light stimulation at 40 Hz effectively mitigated amyloid beta load in aged AD mice. This non-invasive therapeutic approach, however, is not yet thoroughly studied and lacks cell-type-specific characterization. In particular, the role of PV-interneurons in this phenomenon is not yet clear. Studying the intrinsic physiological properties of these PV-interneurons requires patch clamp electrophysiology, a time intensive and low-throughput neuroscience technique which allows one to record sub-threshold current and voltage membrane changes from individual neurons. Recent advances in the field of patch clamp have automated this laborious process; however, there are still bottlenecks that limit the throughput and yield. Thus, the objective of this proposal is to (1) optimize and leverage automated patch clamp electrophysiology, subsequently (2) explore the spatiotemporal emergence of PV-interneuron dysfunction in AD, and (3) investigate and quantify the effects of 40 Hz light and sound sensory stimulation on PV-interneurons in AD.
- Workflow Status: Published
- Created By: Tatianna Richardson
- Created: 11/29/2022
- Modified By: Tatianna Richardson
- Modified: 11/29/2022