Bi-allelic genetic variants in the translational GTPases GTPBP1 and GTPBP2 cause a distinct identical neurodevelopmental syndrome DOI Creative Commons

Vincenzo Salpietro,

Reza Maroofian, Maha S. Zaki

et al.

The American Journal of Human Genetics, Journal Year: 2023, Volume and Issue: 111(1), P. 200 - 210

Published: Dec. 20, 2023

The homologous genes GTPBP1 and GTPBP2 encode GTP-binding proteins 1 2, which are involved in ribosomal homeostasis. Pathogenic variants were recently shown to be an ultra-rare cause of neurodegenerative or neurodevelopmental disorders (NDDs). Until now, no human phenotype has been linked GTPBP1. Here, we describe individuals carrying bi-allelic that display identical with characterize the overall spectrum protein (1/2)-related disorders. In this study, 20 from 16 families distinct NDDs syndromic facial features investigated by whole-exome (WES) whole-genome (WGS) sequencing. To assess functional impact identified genetic variants, semi-quantitative PCR, western blot, ribosome profiling assays performed fibroblasts affected individuals. We also effect reducing expression CG2017, ortholog GTPBP1/2, fruit fly Drosophila melanogaster. Individuals presented microcephaly, profound impairment, pathognomonic craniofacial features, ectodermal defects. Abnormal vision and/or hearing, progressive spasticity, choreoathetoid movements, refractory epilepsy, brain atrophy part core syndrome. Cell line studies a loss-of-function (LoF) disease-associated but significant abnormalities on profiling. Reduced CG2017 isoforms was associated locomotor impairment Drosophila. conclusion, LoF identical, Mutant knockout flies motor highlighting conserved role for CNS development across species.

Language: Английский

Neuronal wiring diagram of an adult brain DOI Creative Commons
Sven Dorkenwald, Arie Matsliah, Amy Sterling

et al.

Nature, Journal Year: 2024, Volume and Issue: 634(8032), P. 124 - 138

Published: Oct. 2, 2024

Language: Английский

Citations

134
Neuronal wiring diagram of an adult brain DOI Creative Commons
Sven Dorkenwald, Arie Matsliah, Amy Sterling

et al.

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

Published: June 30, 2023

Abstract Connections between neurons can be mapped by acquiring and analyzing electron microscopic (EM) brain images. In recent years, this approach has been applied to chunks of brains reconstruct local connectivity maps that are highly informative, yet inadequate for understanding function more globally. Here, we present the first neuronal wiring diagram a whole adult brain, containing 5×10 7 chemical synapses ∼130,000 reconstructed from female Drosophila melanogaster . The resource also incorporates annotations cell classes types, nerves, hemilineages, predictions neurotransmitter identities. Data products available download, programmatic access, interactive browsing made interoperable with other fly data resources. We show how derive projectome, map projections regions, connectome. demonstrate tracing synaptic pathways analysis information flow inputs (sensory ascending neurons) outputs (motor, endocrine, descending neurons), across both hemispheres, central optic lobes. Tracing subset photoreceptors all way motor illustrates structure uncover putative circuit mechanisms underlying sensorimotor behaviors. technologies open ecosystem FlyWire Consortium set stage future large-scale connectome projects in species.

Language: Английский

Citations

132
Brain-wide representations of behavior spanning multiple timescales and states in C. elegans DOI Creative Commons

Adam A. Atanas,

Jung Soo Kim, Ziyu Wang

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(19), P. 4134 - 4151.e31

Published: Aug. 21, 2023

Changes in an animal's behavior and internal state are accompanied by widespread changes activity across its brain. However, how neurons the brain encode this is impacted poorly understood. We recorded brain-wide diverse motor programs of freely moving C. elegans built probabilistic models that explain each neuron encodes quantitative behavioral features. By determining identities neurons, we created atlas defined classes connectome behavior. Many have conjunctive representations multiple behaviors. Moreover, although many current actions, others integrate recent actions. behavior, identify these flexible nodes connectome. Our results provide a global map cell types

Language: Английский

Citations

47
Ascending neurons convey behavioral state to integrative sensory and action selection brain regions DOI Creative Commons
Chin‐Lin Chen, Florian Aymanns, Ryo Minegishi

et al.

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(4), P. 682 - 695

Published: March 23, 2023

Knowing one's own behavioral state has long been theorized as critical for contextualizing dynamic sensory cues and identifying appropriate future behaviors. Ascending neurons (ANs) in the motor system that project to brain are well positioned provide such signals. However, what ANs encode where they convey these signals remains largely unknown. Here, through large-scale functional imaging behaving animals morphological quantification, we report encoding targeting of hundreds genetically identifiable adult fly, Drosophila melanogaster. We reveal states, specifically conveying self-motion anterior ventrolateral protocerebrum, an integrative hub, discrete actions gnathal ganglia, a locus action selection. Additionally, AN projection patterns within predictive their encoding. Thus, ascending populations poised inform distinct hubs ongoing behaviors may important substrate computations required adaptive behavior.

Language: Английский

Citations

45
Network statistics of the whole-brain connectome of Drosophila DOI Creative Commons
Albert Lin, Runzhe Yang, Sven Dorkenwald

et al.

Nature, Journal Year: 2024, Volume and Issue: 634(8032), P. 153 - 165

Published: Oct. 2, 2024

Language: Английский

Citations

26
The spatial and temporal structure of neural activity across the fly brain DOI Creative Commons
Evan Schaffer, Neeli Mishra, Matthew R Whiteway

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 11, 2023

What are the spatial and temporal scales of brainwide neuronal activity? We used swept, confocally-aligned planar excitation (SCAPE) microscopy to image all cells in a large volume brain adult Drosophila with high spatiotemporal resolution while flies engaged variety spontaneous behaviors. This revealed neural representations behavior on multiple scales. The activity most neurons correlated (or anticorrelated) running flailing over timescales that ranged from seconds minute. Grooming elicited weaker global response. Significant residual not directly was dimensional reflected small clusters spatially organized may correspond genetically defined cell types. These participate dynamics, indicating reflects combination local broadly distributed components. suggests microcircuits highly specified functions provided knowledge larger context which they operate.

Language: Английский

Citations

27
Neural circuit mechanisms underlying context-specific halting in Drosophila DOI Creative Commons

Neha Sapkal,

Nino Mancini,

Divya Sthanu Kumar

et al.

Nature, Journal Year: 2024, Volume and Issue: 634(8032), P. 191 - 200

Published: Oct. 2, 2024

Language: Английский

Citations

15
The fly connectome reveals a path to the effectome DOI Creative Commons
Dean A. Pospisil, Max Jameson Aragon, Sven Dorkenwald

et al.

Nature, Journal Year: 2024, Volume and Issue: 634(8032), P. 201 - 209

Published: Oct. 2, 2024

Language: Английский

Citations

10
Fast, efficient, and accurate neuro-imaging denoising via supervised deep learning DOI Creative Commons
Shivesh Chaudhary, Sihoon Moon, Hang Lu

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Sept. 2, 2022

Volumetric functional imaging is widely used for recording neuron activities in vivo, but there exist tradeoffs between the quality of extracted calcium traces, speed, and laser power. While deep-learning methods have recently been applied to denoise images, their applications downstream analyses, such as recovering high-SNR limited. Further, these require temporally-sequential pre-registered data acquired at ultrafast rates. Here, we demonstrate a supervised deep-denoising method circumvent several applications, including whole-brain imaging, large-field-of-view freely moving animals, complex neurite structures C. elegans. Our framework has 30× smaller memory footprint, fast training inference (50-70 ms); it highly accurate generalizable, further, trained with only small, non-temporally-sequential, independently-acquired datasets (∼500 pairs images). We envision that will enable faster long-term experiments necessary study neuronal mechanisms many behaviors.

Language: Английский

Citations

32
Descending neuron population dynamics during odor-evoked and spontaneous limb-dependent behaviors DOI Creative Commons
Florian Aymanns, Chin‐Lin Chen, Pavan P Ramdya

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Oct. 25, 2022

Deciphering how the brain regulates motor circuits to control complex behaviors is an important, long-standing challenge in neuroscience. In fly, Drosophila melanogaster , this coordinated by a population of ~ 1100 descending neurons (DNs). Activating only few DNs known be sufficient drive like walking and grooming. However, what additional role larger plays during natural remains largely unknown. For example, they may modulate core behavioral commands or comprise parallel pathways that are engaged depending on sensory context. We evaluated these possibilities recording populations nearly 100 individual tethered flies while generated limb-dependent behaviors, including found largest fraction recorded encode fewer active head grooming resting. A large walk-encoding turning far weakly speed. Although odor context does not determine which behavior-encoding recruited, odors rather than behaviors. Lastly, we illustrate one can identify from DN recordings using their spatial, functional, morphological properties. These results set stage for comprehensive, population-level understanding brain’s signals regulate actions.

Language: Английский

Citations

32