Aging-Dependent Loss of Connectivity in Alzheimer’s Model Mice with Rescue by mGluR5 Modulator

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 16, 2023

Abstract Amyloid accumulation in Alzheimer’s disease (AD) is associated with synaptic damage and altered connectivity brain networks. While measures of amyloid biochemical changes mouse models have utility for translational studies certain therapeutics, preclinical analysis using clinically relevant fMRI has not been well developed agents intended to improve neural Here, we conduct a longitudinal study double knock-in model AD ( App NL-G-F /hMapt ), monitoring by means resting-state fMRI. the 4-month-old mice are indistinguishable from wild-type controls (WT), decreased default-mode network significant relative WT 6 months age pronounced 9 age. In second cohort 20-month-old persistent functional deficits WT, assess impact two-months oral treatment silent allosteric modulator mGluR5 (BMS-984923) known rescue density. Functional aged reversed mGluR5-directed treatment. The application enabled us define time trajectory AD-related connectivity, demonstrate translatable metric emergence, progression, response synapse-rescuing

Language: Английский

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Repetitive mild closed-head injury induced synapse loss and increased local BOLD-fMRI signal homogeneity

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

Published: May 27, 2024

Repeated mild head injuries due to sports, or domestic violence and military service are increasingly linked debilitating symptoms in the long term. Although may take decades manifest, potentially treatable neurobiological alterations must begin shortly after injury. Better means diagnose treat traumatic brain injuries, requires an improved understanding of mechanisms underlying progression through which they can be measured. Here, we employ a repetitive closed-head injury (rmTBI) chronic variable stress (CVS) mouse model investigate emergent structural functional abnormalities. Brain imaging is achieved with [

Language: Английский

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Open Science Under Debate: Disentangling the Interest on Twitter and Scholarly Research

SAGE Open, Journal Year: 2024, Volume and Issue: 14(3)

Published: July 1, 2024

Open science movement gains attention since it might enable a second scientific revolution that fundamentally changes research methods and standards across science. However, the discussion topics towards opens both from academia environments outside scholarly communication process have not been formally identified. This paper contributes to end by analyzing 145,716 open-science-related tweets 3,200 papers in Scopus 2011 2022. The results show there is increasing interest about open on Twitter academia. There are similar foci for public Scopus, including cloud computing COVID-19 pandemic. When focus events citizen science, more concerned detailed aspects novel innovation research. findings policy-maker offering evidence facilitate policies practices.

Language: Английский

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Nonparanormal graph quilting with applications to calcium imaging

Stat, Journal Year: 2023, Volume and Issue: 12(1)

Published: Jan. 1, 2023

Abstract Probabilistic graphical models have become an important unsupervised learning tool for detecting network structures a variety of problems, including the estimation functional neuronal connectivity from two‐photon calcium imaging data. However, in context imaging, technological limitations only allow partially overlapping layers neurons brain region interest to be jointly recorded. In this case, graph full data requires inference edge selection when many pairs no simultaneous observations. This leads quilting problem, which seeks estimate presence block‐missingness empirical covariance matrix. Solutions problem previously been studied Gaussian models; however, neural activity are often non‐Gaussian, thereby requiring more flexible modelling approach. Thus, our work, we study two approaches nonparanormal based on copula model, namely, maximum likelihood procedure and low rank‐based framework. We provide theoretical guarantees recovery former approach under similar conditions those developed setting, investigate performance both methods using simulations as well real Our yield scientifically meaningful estimates compared existing set.

Language: Английский

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Multimodal measures of spontaneous brain activity reveals both common and divergent patterns of cortical functional organization

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Dec. 15, 2022

Abstract Work in humans and animals shows that the brain can be decomposed into large-scale functional networks. Whereas most studies, especially humans, use blood-oxygenation-level-dependent (BOLD) signal, relationship between BOLD neuronal activity is complex incompletely understood. This limits our ability to interpret apply measures derived from fMRI-BOLD. Here, we employ wide-field Ca 2+ imaging simultaneously recorded with fMRI-BOLD highly-sampled mice expressing GCaMP6f excitatory neurons. These unique data enabled us characterize similarities differences networks discoverable by each modality. Importantly, applied a network partitioning approach uses mixed-membership algorithm, which allows regions participate multiple varying strengths. contrasts assuming belong only one network. Our findings demonstrate (1) are detected via signals. (2) There considerable overlapping—as opposed disjoint—network organization evident both modalities. (3) Large-scale determined signals at low temporal frequencies (0.01 – 0.5 Hz )—as higher (0.5 5 )—are more similar those BOLD. (4) Despite many similarities, emerge across modes including spatial distribution of membership diversity (the extent affiliate networks). In sum, neurons confirms mouse cortex functionally organized overlapping manner reflects many, but not all, properties observable simultaneous fMRI-BOLD; affirming neural origins patterns clinically accessible neuroimaging

Language: Английский

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