Defining the Effects of A-Synuclein Pathology on the Amygdala Circuitry: Relevance to Neuropsychiatric Dysfunction in Parkinson's Disease
Abstract
We propose to use an experimental approach that recapitulates alpha-synuclein (a-syn) pathology in the amygdala and allows us to define its impact on the amygdala circuitry (at the molecular and cellular levels) and on emotional behavior. The objective of this project is to improve our understanding of the amygdala dysfunction associate with a-syn pathology, contributing to the design of better treatments for psychiatric symptoms in PD. In Year 1, following intrastriatal PBS or PFFs injections, we determined the temporal development of a-syn pathology in the amygdala, performed behavior studies to assess the impact of a-syn pathology on motor and nonmotor function of mice at 1, 3,and 6 mpi. We observed a gradual accumulation of a-syn pathology in the amygdala, which peaked at 3 mpi, and the pathology caused mild motor deficits at 6 mpi, indicating the associated circuits dysfunction. Using electrophysiology, we detected dynamic changes in cellular properties of amygdala neurons from 1 to 3 mpi, and such changes were caused by different molecular and circuit mechanisms. This is the first set of experimental evidence showing pathophysiological consequences of a-syn pathology on the amygdala function. We are currently continuing on this line of work to seek in-depth mechanistic understanding of circuitry dysfunction related to the amygdala. Part of this supported work contributed to a recent publication on eLife .
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1193032
Entities
People
- Hong-yuan Chu