Biology subjects

Bjork, R. T.

Publications and source records attributed to Bjork, R. T..

2 recordsLinked to original sources

bioRxiv2025

Alpha-synuclein overexpression reduces neural activity within a basal ganglia vocal nucleus in a zebra finch model

Changes in vocal pitch, loudness, and timing are prevalent in Parkinsons Disease (PD) and a target for early intervention and treatment. The neural mechanisms underlying these impairments are not understood, motivating work in animal models. The adult male zebra finch songbird is uniquely poised for these studies given vocally-dedicated brain nuclei and a quantifiable output (birdsong). Our prior publication revealed that injection of an adeno-associated virus (AAV5) expressing the human (h) alpha-synuclein (hSNCA, a-syn) gene into basal ganglia vocal nucleus Area X results in elevated insoluble a-syn protein and parkinsonian-like changes including softer, shorter, and reduced vocalizations compared to controls. Here, we test the hypothesis that AAV-hSNCA overexpression reduces the firing rate of specific neuronal sub-types in Area X using in vivo recordings in anesthetized finches. Five classes of neurons were differentiated in AAV-treated finches based on waveform width (narrow vs. wide) and firing rates (low vs. fast). Wide-waveform/low-rate activity is a consistent feature of striatal medium spiny neurons (MSNs), a dominant cell type in Area X and in mammalian basal ganglia. Reduced firing rates and enhanced post-peak rebound were detected in the AAV-hSNCA group for putative MSN neurons compared to AAV controls. No differences in firing rate nor waveform shape were detected for the narrow waveform neurons. Our findings provide the first characterization of early a-syn-driven neural activity changes in vocal control neurocircuitry.

neuroscience↗

bioRxiv2022

Modelling dementia in Drosophila uncovers shared and specific targets of TDP-43 proteinopathy across ALS and FTD relevant circuits

Amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD) comprise a spectrum of neurodegenerative diseases linked to TDP-43 proteinopathy, which at the cellular level, is characterized by loss of nuclear TDP-43 and accumulation of cytoplasmic TDP-43 puncta that ultimately cause RNA processing defects including dysregulation of splicing, mRNA transport and translation. Complementing our previous models of ALS, here we report a novel model of FTD based on overexpression of TDP-43 in the Drosophila mushroom body (MB) circuit. This model recapitulates several aspects of FTD pathology including age-dependent neuronal loss, and nuclear depletion and cytoplasmic accumulation of TDP-43, accompanied by behavioral deficits in working memory and sleep that occur before axonal degeneration ensues. RNA immunoprecipitations identify several candidate mRNA targets of TDP-43 in MBs, some of which are unique to the MB circuit while others are shared with motor neurons. Among the latter is the glypican Dally-like-protein (Dlp), a modulator of Wg/Wnt signaling. Using genetic interactions we show that overexpression of Dlp in MBs mitigates TDP-43 dependent working memory deficits. These results highlight the utility of modelling TDP-43 proteinopathy in Drosophila and provide a novel platform for studying the molecular mechanisms underlying FTD, and potentially uncovering shared and circuit specific vulnerabilities in ALS/FTD.

neuroscience↗