Laura Volpicelli-Daley, PhD
Name of Institution:
University of Alabama at Birmingham, Birmingham, AL
mGluR4 activation to rescue amygdala defects caused by aggregated alpha-synuclein
Dr. Laura Volpicelli-Daley is an Associate Professor of Neurology at University of Alabama at Birmingham, and Parkinson Association of Alabama Endowed Professor. She earned her PhD in Neuroscience at Emory University in Atlanta, GA, and received training in Cell Biology and neurodegenerative disease at both Yale University in New Haven, CT, and University of Pennsylvania in Philadelphia, PA.. The goal of Dr. Volpicelli-Daley’s lab is to prevent the progression Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB) which are characterized by abnormal α-synuclein. The lab is interested in how α-synuclein inclusions in limbic and cortical brain areas disrupt neuronal function and contribute to cognitive changes in PD and DLB. The lab is also interested in how genes implicated in PD and DLB such as LRRK2, GBA1 and MAPT, impact normal α-synuclein localization in neurons, formation of abnormal α-synuclein aggregates, and their impact on neuronal function and behavioral phenotypes.
To determine how abnormal aggregates of α-synuclein disrupt neurotransmission in the amygdala and contribute to cognitive and psychiatric dysfunction (such as anxiety) in PD.
Abnormal aggregates of α-synuclein characterize PD and DLB. These aggregates are particularly abundant in the amygdala, a brain region critical for emotional control. Our lab has shown using a mouse model of α-synuclein aggregates, that these inclusions cause behavioral defects associated with amygdala dysfunction. Our project seeks to determine how abnormal aggregates of α-synuclein disrupt neurotransmission in the amygdala.
α-synuclein aggregates can be generated in a test tube that resemble those found in the PD brains, forming a structure called amyloid fibrils. These fibrils can be injected into the mouse brain where they gain access to the neuron and corrupt the normal α-synuclein to form inclusions in brain regions such as the cortex and amygdala. Using this mouse model of α-synuclein aggregation, we will use biosensor and neurochemistry techniques to determine how the inclusions cause changes in neurotransmitters in the amygdala. We will also treat these mice with activators of metabotropic glutamate receptors which have been shown in other mouse models of PD to rescues amygdala dysfunction.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
If successful, this project could determine if pharmacologic compounds targeting metabotropic glutamate receptors could rescue defects in the amygdala and prevent development of cognitive and psychiatric disturbances in PD.