Nucleus accumbens circuit disinhibits lateral hypothalamus glutamatergic neurons contributing to morphine withdrawal memory in male mice DOI Creative Commons
Sheng Huan, Chao Lei, Yu Yuan

et al.

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

Published: Jan. 5, 2023

The lateral hypothalamus (LH) is physiologically critical in brain functions. LH also plays an important role drug addiction. However, neural circuits underlying involvement of addiction remain obscure. In the present study,our results showed that male mice, during context-induced expression morphine withdrawal memory, glutamatergic neurons played role; dopamine D1 receptor-expressing medium spiny (D1-MSNs) projecting from core nucleus accumbens (NAcC) to were upstream circuit activate neurons; D1-MSNs NAcC activated through inhibiting local gamma-aminobutyric acid (GABA) neurons. These suggest disinhibited by importantly contribute memory.

Language: Английский

What is a cell type and how to define it? DOI Creative Commons
Hongkui Zeng

Cell, Journal Year: 2022, Volume and Issue: 185(15), P. 2739 - 2755

Published: July 1, 2022

Language: Английский

Citations

278
The emerging landscape of spatial profiling technologies DOI
Jeffrey R. Moffitt, Emma Lundberg, Holger Heyn

et al.

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(12), P. 741 - 759

Published: July 20, 2022

Language: Английский

Citations

277
The expanding vistas of spatial transcriptomics DOI
Luyi Tian, Fei Chen, Evan Z. Macosko

et al.

Nature Biotechnology, Journal Year: 2022, Volume and Issue: 41(6), P. 773 - 782

Published: Oct. 3, 2022

Language: Английский

Citations

260
Molecular and spatial signatures of mouse brain aging at single-cell resolution DOI Creative Commons
William E. Allen, Timothy R. Blosser, Zuri A. Sullivan

et al.

Cell, Journal Year: 2022, Volume and Issue: 186(1), P. 194 - 208.e18

Published: Dec. 28, 2022

The diversity and complex organization of cells in the brain have hindered systematic characterization age-related changes its cellular molecular architecture, limiting our ability to understand mechanisms underlying functional decline during aging. Here, we generated a high-resolution cell atlas aging within frontal cortex striatum using spatially resolved single-cell transcriptomics quantified gene expression spatial major types these regions over mouse lifespan. We observed substantially more pronounced state, expression, non-neuronal neurons. Our data revealed signatures glial immune activation aging, particularly enriched subcortical white matter, identified both similarities notable differences cell-activation patterns induced by systemic inflammatory challenge. These results provide critical insights into inflammation brain.

Language: Английский

Citations

239
Molecularly defined and spatially resolved cell atlas of the whole mouse brain DOI Creative Commons
Meng Zhang, Xingjie Pan, Won Jung

et al.

Nature, Journal Year: 2023, Volume and Issue: 624(7991), P. 343 - 354

Published: Dec. 13, 2023

In mammalian brains, millions to billions of cells form complex interaction networks enable a wide range functions. The enormous diversity and intricate organization have impeded our understanding the molecular cellular basis brain function. Recent advances in spatially resolved single-cell transcriptomics enabled systematic mapping spatial molecularly defined cell types tissues1-3, including several regions (for example, refs. 1-11). However, comprehensive atlas whole is still missing. Here we imaged panel more than 1,100 genes approximately 10 million across entire adult mouse brains using multiplexed error-robust fluorescence situ hybridization12 performed resolved, expression profiling at whole-transcriptome scale by integrating hybridization RNA sequencing data. Using this approach, generated 5,000 transcriptionally distinct clusters, belonging 300 major types, with high resolution. Registration common coordinate framework allowed quantifications cell-type composition individual regions. We further identified modules characterized compositions gradients featuring gradual changes cells. Finally, high-resolution map cells, each transcriptome-wide profile, us infer cell-type-specific interactions between hundreds pairs predict (ligand-receptor) functional implications these cell-cell interactions. These results provide rich insights into architecture foundation for investigations neural circuits their dysfunction health disease.

Language: Английский

Citations

220
Spatial atlas of the mouse central nervous system at molecular resolution DOI Creative Commons
Hailing Shi, Yichun He, Yiming Zhou

et al.

Nature, Journal Year: 2023, Volume and Issue: 622(7983), P. 552 - 561

Published: Sept. 27, 2023

Abstract Spatially charting molecular cell types at single-cell resolution across the 3D volume is critical for illustrating basis of brain anatomy and functions. Single-cell RNA sequencing has profiled in mouse 1,2 , but cannot capture their spatial organization. Here we used an situ method, STARmap PLUS 3,4 to profile 1,022 genes a voxel size 194 × 345 nm 3 mapping 1.09 million high-quality cells adult spinal cord. We developed computational pipelines segment, cluster annotate 230 by gene expression 106 tissue regions niche expression. Joint analysis enabled systematic cell-type nomenclature identification architectures that were undefined established anatomy. To create transcriptome-wide atlas, integrated measurements with published RNA-sequencing atlas 1 imputing profiles 11,844 genes. Finally, delineated viral tropisms brain-wide transgene delivery tool, AAV-PHP.eB 5,6 . Together, this annotated dataset provides resource integrates accessibility genetic manipulation mammalian central nervous system.

Language: Английский

Citations

110
The molecular cytoarchitecture of the adult mouse brain DOI Creative Commons
Jonah Langlieb, Nina Sachdev, Karol S. Balderrama

et al.

Nature, Journal Year: 2023, Volume and Issue: 624(7991), P. 333 - 342

Published: Dec. 13, 2023

Abstract The function of the mammalian brain relies upon specification and spatial positioning diversely specialized cell types. Yet, molecular identities types their positions within individual anatomical structures remain incompletely known. To construct a comprehensive atlas in each structure, we paired high-throughput single-nucleus RNA sequencing with Slide-seq 1,2 —a recently developed transcriptomics method near-cellular resolution—across entire mouse brain. Integration these datasets revealed type composition neuroanatomical structure. Cell diversity was found to be remarkably high midbrain, hindbrain hypothalamus, most clusters requiring combination at least three discrete gene expression markers uniquely define them. Using data, framework for genetically accessing type, comprehensively characterized neuropeptide neurotransmitter signalling, elucidated region-specific specializations activity-regulated ascertained heritability enrichment neurological psychiatric phenotypes. These available as an online resource ( www.BrainCellData.org ), should find diverse applications across neuroscience, including construction new genetic tools prioritization specific circuits study diseases.

Language: Английский

Citations

97
SODB facilitates comprehensive exploration of spatial omics data DOI
Zhiyuan Yuan, Wentao Pan, Xuan Zhao

et al.

Nature Methods, Journal Year: 2023, Volume and Issue: 20(3), P. 387 - 399

Published: Feb. 16, 2023

Language: Английский

Citations

70
Spatial transcriptomics reveal neuron–astrocyte synergy in long-term memory DOI Creative Commons
Wenfei Sun, Zhihui Liu, Xian Jiang

et al.

Nature, Journal Year: 2024, Volume and Issue: 627(8003), P. 374 - 381

Published: Feb. 7, 2024

Abstract Memory encodes past experiences, thereby enabling future plans. The basolateral amygdala is a centre of salience networks that underlie emotional experiences and thus has key role in long-term fear memory formation 1 . Here we used spatial single-cell transcriptomics to illuminate the cellular molecular architecture memory. We identified transcriptional signatures subpopulations neurons astrocytes were memory-specific persisted for weeks. These implicate neuropeptide BDNF signalling, MAPK CREB activation, ubiquitination pathways, synaptic connectivity as components Notably, upon formation, neuronal subpopulation defined by increased Penk decreased Tac expression constituted most prominent component engram amygdala. changes observed both with RNA sequencing single-molecule intact slices, providing rich map engram. data enabled us determine this interacts adjacent astrocytes, functional experiments show require interactions encode

Language: Английский

Citations

58
Neuronal types in the mouse amygdala and their transcriptional response to fear conditioning DOI Creative Commons
Hannah Hochgerner, Shelly Singh, Muhammad Tibi

et al.

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(12), P. 2237 - 2249

Published: Oct. 26, 2023

Abstract The amygdala is a brain region primarily associated with emotional response. use of genetic markers and single-cell transcriptomics can provide insights into behavior-associated cell state changes. Here we present detailed cell-type taxonomy the adult mouse during fear learning memory consolidation. We perform RNA sequencing on naïve fear-conditioned mice, identify 130 neuronal types validate their spatial distributions. A subset all transcriptionally responsive to retrieval. activated engram cells upregulate activity-response genes coordinate expression neurite outgrowth, synaptic signaling, plasticity development. known previously undescribed candidate learning. Our molecular atlas may be used generate hypotheses unveil neuron neural circuits regulating component memory.

Language: Английский

Citations

49