Cortical Alpha-synuclein Preformed Fibrils Do Not Affect Interval Timing in Mice

Overview

Journal Neurosci Lett

Specialty Neurology

Date 2021 Oct 3

PMID 34601038

Citations 7

Authors

Qiang Zhang

Hisham Abdelmotilib

Travis Larson

Cameron Keomanivong

Mackenzie Conlon

Georgina M Aldridge

Nandakumar S Narayanan

Affiliations

Soon will be listed here.

Abstract

One hallmark feature of Parkinson's disease (PD) is Lewy body pathology associated with misfolded alpha-synuclein. Previous studies have shown that striatal injection of alpha-synuclein preformed fibrils (PFF) can induce misfolding and aggregation of native alpha-synuclein in a prion-like manner, leading to cell death and motor dysfunction in mouse models. Here, we tested whether alpha-synuclein PFFs injected into the medial prefrontal cortex results in deficits in interval timing, a cognitive task which is disrupted in human PD patients and in rodent models of PD. We injected PFF or monomers of human alpha-synuclein into the medial prefrontal cortex of mice pre-injected with adeno-associated virus (AAV) coding for overexpression of human alpha-synuclein or control protein. Despite notable medial prefrontal cortical synucleinopathy, we did not observe consistent deficits in fixed-interval timing. These results suggest that cortical alpha-synuclein does not reliably disrupt fixed-interval timing.

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