{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:59:48Z","timestamp":1768525188004,"version":"3.49.0"},"posted":{"date-parts":[[2024,5,15]]},"group-title":"Neuroscience","reference-count":46,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Parkinson\u2019s disease (PD) and Dementia with Lewy bodies (DLB) are characterized by neuronal \u03b1-synuclein (\u03b1-syn) inclusions termed Lewy Pathology, which are abundant in the amygdala. The basolateral amygdala (BLA), in particular, receives projections from the thalamus and cortex. These projections play a role in cognition and emotional processing, behaviors which are impaired in \u03b1-synucleinopathies. To understand if and how pathologic \u03b1-syn impacts the BLA requires animal models of \u03b1-syn aggregation. Injection of \u03b1-synuclein pre-formed fibrils (PFFs) into the striatum induces robust \u03b1-synuclein aggregation in excitatory neurons in the BLA that corresponds with reduced contextual fear conditioning. At early time points after aggregate formation, cortico-amygdala excitatory transmission is abolished. The goal of this project was to determine if \u03b1-syn inclusions in the BLA induce synaptic degeneration and\/or morphological changes. In this study, we used C57BL\/6J mice injected bilaterally with PFFs in the dorsal striatum to induce \u03b1-syn aggregate formation in the BLA. A method was developed using immunofluorescence and three-dimensional reconstruction to analyze excitatory cortico-amygdala and thalamo-amygdala presynaptic terminals closely juxtaposed to postsynaptic densities. The abundance and morphology of synapses were analyzed at 6- or 12-weeks post-injection of PFFs. \u03b1-Syn aggregate formation in the BLA did not cause a significant loss of synapses, but cortico-amygdala and thalamo-amygdala presynaptic terminals and postsynaptic densities with aggregates of \u03b1-synuclein show increased volumes, similar to previous findings in human DLB cortex, and in non-human primate models of PD. Transmission electron microscopy showed that PFF-injected mice showed reduced intervesicular distances similar to a recent study showing phospho-serine-129 \u03b1-synuclein increases synaptic vesicle clustering. Thus, pathologic \u03b1-synuclein causes major alterations to synaptic architecture in the BLA, potentially contributing to behavioral impairment and amygdala dysfunction observed in synucleinopathies.<\/jats:p>","DOI":"10.1101\/2024.05.15.594419","type":"posted-content","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T04:10:20Z","timestamp":1715832620000},"source":"Crossref","is-referenced-by-count":0,"title":["Cortico-amygdala synaptic structural abnormalities produced by templated aggregation of \u03b1-synuclein"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9708-6119","authenticated-orcid":false,"given":"Nolwazi Z.","family":"Gcwensa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dreson L.","family":"Russell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khaliah Y.","family":"Long","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8871-2453","authenticated-orcid":false,"given":"Charlotte F.","family":"Brzozowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinran","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3813-8577","authenticated-orcid":false,"given":"Karen L.","family":"Gamble","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5814-9412","authenticated-orcid":false,"given":"Rita M.","family":"Cowell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8934-4018","authenticated-orcid":false,"given":"Laura 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