{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T19:11:04Z","timestamp":1788462664483,"version":"build-2803163510"},"posted":{"date-parts":[[2023,2,3]]},"group-title":"Animal Behavior and Cognition","reference-count":65,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Parkinson\u2019s disease dementia (PDD) and dementia with Lewy bodies (DLB) are characterized by diffuse spread of alpha-synuclein (\u03b1-syn) throughout the brain. Patients with PDD and DLB have a neuropsychological pattern of deficits that include executive dysfunction, such as abnormalities in planning, timing, working memory, and behavioral flexibility. The prefrontal cortex (PFC) plays a major role in normal executive function and often develops \u03b1-syn aggregates in DLB and PDD. To investigate the consequences of \u03b1-syn pathology in the cortex, we injected human \u03b1-syn pre-formed fibrils into the PFC of wildtype mice. We report that PFC PFFs: 1) induced \u03b1-syn aggregation in multiple cortical and subcortical regions with sparse aggregation in midbrain and brainstem nuclei; 2) did not affect interval timing or spatial learning acquisition but did mildly alter behavioral flexibility as measured by intraday reversal learning; 3) increased open field exploration; and 4) did not affect susceptibility to an inflammatory challenge. This model of cortical-dominant pathology aids in our understanding of how local \u03b1-syn aggregation might impact some symptoms in PDD and DLB.<\/jats:p>","DOI":"10.1101\/2023.01.31.526365","type":"posted-content","created":{"date-parts":[[2023,2,4]],"date-time":"2023-02-04T00:05:14Z","timestamp":1675469114000},"source":"Crossref","is-referenced-by-count":2,"title":["Alpha-synuclein pre-formed fibrils injected into prefrontal cortex primarily spread to cortical and subcortical structures and lead to isolated behavioral symptoms"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0488-1792","authenticated-orcid":false,"given":"Matthew 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