Article Archive

The used array fiber photometry in mice to investigate how ACh release across the striatum evolves during learning and extinction of Pavlovian associations.

The authors tested different detergents for their ability to solubilize human α-synuclein carrying the pathological mutation A53T from the brains of aged flies.

Evidence is mounting that injury and inflammation in the gut and locus coeruleus (LC), respectively, underlie Parkinson's disease symptoms, and the injury of these systems is central to the progression of PD. In this study, the authors generate a novel two-hit mouse model that captures both features.

To identify shared and distinct features of the PD and IBD microbiome, the authors performed a joint analysis of 54 PD, 26 IBD, and 16 healthy control gut metagenomes recruited from clinics at the University of Florida and directly compared the gut microbiomes from PD and IBD persons.

Many motor behaviors require learning through repeated practice. Among the brain’s motor regions, the cortico-basal ganglia circuit is particularly crucial for acquiring and executing motor skills, and neuronal activity in these regions is directly linked to movement parameters. Here, the authors detail the cortico-basal ganglia plasticity in motor learning.

This article summarizes the most up-to-date knowledge in pharmacomicrobiomics in PD, and discusses how the manipulation of gut microbiota represents a potential new therapeutic avenue for PD.

The authors explored the cellular and synaptic mechanisms of levodopa-induced dyskinesia (LID), a complication of Parkinson’s disease therapy characterized by involuntary movements. Findings suggest how the intrinsic and synaptic properties of heterogeneous dMSN subpopulations integrate to support action selection.

Publication: These results suggest that the limited efficiency of autophagy in clearing polyQ aggregates is due to the inability of autophagosomes to interact productively with the non-deformable, fibrillar disease aggregates. View original preprint. 

The authors investigated the impact of SJ1 on DA neurons using iPSC-derived SJ1 KO and SJ1RQKI DA neurons and their isogenic controls. Results suggest that SJ1 may contribute to the control of ciliary protein dynamics in DA neurons, with implications on cilia-mediated signaling.

Here, the authors discuss how the intersection of stem cell biology, population genetics, and cellular genomics can help resolve the functional consequences of human genetic variation.

Here, the authors introduce PINNACLE, a geometric deep-learning approach that generates context-aware protein representations. PINNACLE’s ability to adjust its outputs on the basis of the context in which it operates paves the way for large-scale context-specific predictions in biology.

Aging is the biggest risk factor for the development of Alzheimer’s disease (AD). Here, the authors performed a whole-genome CRISPR screen to identify regulators of neuronal age and show that the neddylation pathway regulates both cellular age and AD neurodegeneration in a human stem cell model.

COVID-19 patients commonly present with signs of central nervous system and/or peripheral nervous system dysfunction. Here, the authors show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Here, the authors map the initiating immune events at the site of infection at the earliest stages with the goal of shedding light on the earliest mechanisms triggering immune-mediated pathological processes relevant to Parkinson's disease.

Loss-of-function mutations in the ATP10B gene have been identified in Parkinson’s disease patients. Previous studies have shown compromised lysosomal functionality upon ATP10B knockdown in human cell lines and primary cortical neurons. However, its role in vivo and specifically in the nigrostriatal dopaminergic system remains poorly understood.

This review focuses on the inherent neurobiology of nigral DAergic neurons and how such neurobiology impacts the primary mechanism of neurotoxicity.

In this study, heterozygous expression of a common glucocerebrosidase variant, namely the L444P mutation, was found to exacerbate α-synuclein aggregation and spreading in a mouse model of Parkinson-like pathology targeting neurons of the medullary vagal system.

Humans increase the speed of their movements when motivated by incentives. The interplay between incentivization and motor output is pertinent for unpacking the profiles of circuits that link the basal ganglia with motor cortical areas. Team Strick analyzed the profile of two circuits involving putamen and motor cortical areas.

Motor cortical regions have undergone evolutionary expansion and specialization from rodents to primates. Studying these regions in non-human primates (NHPs) is relevant to understanding motor control in NHP models of movement disorders. The use of calcium imaging and miniature microscopes allows the study of multiple individual neurons.