Modulation of Neural Spiking in Motor Cortex–Cerebellar Networks during Sleep Spindles

eNeuro, Journal Year: 2024, Volume and Issue: 11(5), P. ENEURO.0150 - 23.2024

Published: April 19, 2024

Sleep spindles appear to play an important role in learning new motor skills. Motor skill engages several brain regions with two areas being the cortex (M1) and cerebellum (CB). However, neurophysiological processes these during sleep, especially how spindle oscillations affect local cross-region spiking, are not fully understood. We recorded activity from M1 cerebellar eight rats spontaneous investigate sleep related spiking as well spiking. found that firing was significantly changed both CB spindles, this occurred at a preferred phase of spindle. On average, neurons showed most or peaks. These also developed preferential locking cross-area greatest phase-locking value peaks; however, significant for when compared spindles. Additionally, we percentage task-modulated cells fired nonuniform spike distribution M1/CB peaks were greater learned reach-to-grasp task robustly. Finally, band LFP coherence (for LFPs) positive correlation success rate task. findings support idea recruit participate awake memory consolidation.

Language: Английский

A variant of the autophagic receptor NDP52 counteracts phospho-TAU accumulation and emerges as a protective factor for Alzheimer Disease

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 14, 2024

ABSTRACT Selective elimination of early pathological TAU species may be a promising therapeutic strategy to reduce accumulation that contributes neurodegeneration and hallmarks Alzheimer disease (AD). By performing genetic analysis cohort 435 patients with AD, we defined the NDP52 GE variant (rs550510) autophagic receptor (also known as CALCOCO2) protective factor for AD. We provide evidence in vitro systems Drosophila melanogaster model TAU-induced reduces forms through process rescues typical neurodegenerative phenotypes induced by hTAU-toxicity. More importantly, showed is much more effective this respect than WT . Mechanistically, directly binds phospho-TAU, bind them comparable efficiency. On contrary, machinery (LC3C LC3B) efficiently also first time direct target protein phosphatase 2A (PP2A) , opening way possibility fine-tune function Finally, found positive correlation between worldwide distribution allele encoding incidence or prevalence Overall, our work highlights resilience AD shows robust effectiveness drive degradation.

Language: Английский

Long-term motor and cognitive outcome of Deep Brain Stimulation in GBA-PD: the Italian PARKNET study

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 28, 2024

Abstract Deep brain stimulation (DBS) is an established therapeutic option for Parkinson Disease (PD), with demonstrated efficacy on motor symptoms also in patients carrying GBA1 variants (GBA-PD). However, it was recently suggested that DBS may accelerate cognitive decline this frequent genetic subgroup, raising major concerns its indication. Primary aim of study to investigate the possible additive effects genotype and implant deterioration other non-motor features long term. As secondary aims, we assessed clinical outcomes DBS-GBA-PD stratified by variant classes (severe/complex, mild, risk, unknown), different targets (subthalamic nucleus or globus pallidus). This a multicenter retrospective, controlled, Italian cohort involving 15 tertiary level Movement Disorder Centers contributing PARKNET cohort. Demographic, motor, were collected at baseline after 1, 3 5 years, between years 2005 2021. We selected 615 PD participants who either underwent surgery (430 DBS-nonGBA-PD 109 DBS-GBA-PD) fulfilled same criteria eligibility but eventually not operated (76 nonDBS-GBA-PD). Assessments included features, as well long-term complications, across all groups time points. Within-group longitudinal outcome changes, between-group differences, subgroups analyses performed. At baseline, three cohorts largely matched demographic, features. Longitudinally, both showed marked improvements quality life, benefit which absent nonDBS-GBA-PD. Cognitive deterioration, hallucinations urinary problems, significantly increased GBA-PD compared nonGBA-PD, regardless DBS. No relevant differences emerged upon stratification targets, up surgery. represents valid GBA-PD, generates prolonged benefits life while modifying occurrence

Language: Английский