Excitatory synaptic structural abnormalities produced by templated aggregation of α-syn in the basolateral amygdala
Nolwazi Z Gcwensa1, Dreson L Russell1, Khaliah Y Long1
1Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Neurobiology of Disease
|July 7, 2024
Summary
Pathologic alpha-synuclein (α-syn) aggregates in the basolateral amygdala (BLA) alter synaptic structure, not cause loss. These changes in synaptic architecture may explain behavioral impairments in synucleinopathies like Parkinson's disease.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) feature alpha-synuclein (α-syn) Lewy pathology, particularly in the amygdala.
- The basolateral amygdala (BLA) is crucial for cognition and emotion, behaviors impaired in α-synucleinopathies.
Purpose of the Study:
- To investigate if α-syn inclusions in the BLA induce synaptic degeneration or morphological changes.
- To analyze the impact of α-syn aggregation on synaptic architecture in the BLA using an animal model.
Main Methods:
- Induced α-syn aggregate formation in the BLA of C57BL/6J mice via striatal injection of α-syn pre-formed fibrils (PFFs).
- Developed a method using immunofluorescence and 3D reconstruction to analyze cortico-amygdala and thalamo-amygdala presynaptic terminals and postsynaptic densities.
- Utilized transmission electron microscopy to examine synaptic vesicle arrangement.
Main Results:
- α-Syn aggregate formation did not significantly reduce synapse numbers in the BLA.
- Presynaptic terminals and postsynaptic densities containing α-syn aggregates showed increased volumes.
- Synapses exhibited reduced inter-vesicular distances, indicating altered synaptic vesicle clustering.
Conclusions:
- Pathologic α-syn causes significant alterations to synaptic architecture within the BLA.
- These synaptic changes likely contribute to the observed behavioral impairments and amygdala dysfunction in synucleinopathies.
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