Regulation of input excitability in human and mouse parvalbumin interneurons by Kir potassium channels DOI Creative Commons
Szabina Furdan,

Abdennour Douida,

Emőke Bakos

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Compared to rodents, inhibitory interneurons in the human neocortex exhibit high input excitability because of reduced passive ion leakage across their extracellular membrane. However, regulation intrinsic by voltage-gated channels activated over a wide range membrane potentials remains poorly understood. We performed whole-cell patch-clamp microelectrode recordings mouse and neocortical slices obtained from surgically resected non-pathological brain tissue finding that Kir control electrical resistance parvalbumin (Pvalb) neurons an identical manner mouse. Molecular analyses revealed predominantly Kir3.1 Kir3.2 Pvalb both species. Using synaptically connected neuron pairs computational model, we demonstrated physiological activation inhibits during postsynaptic evoked presynaptic neurogliaform cells. The similarity Kir-mediated inhibition species suggests it is archetypal property neurons.

Language: Английский

Signature morphoelectric properties of diverse GABAergic interneurons in the human neocortex DOI
Brian Lee, Rachel Dalley, Jeremy A. Miller

et al.

Science, Journal Year: 2023, Volume and Issue: 382(6667)

Published: Oct. 12, 2023

Human cortex transcriptomic studies have revealed a hierarchical organization of γ-aminobutyric acid-producing (GABAergic) neurons from subclasses to high diversity more granular types. Rapid GABAergic neuron viral genetic labeling plus Patch-seq (patch-clamp electrophysiology single-cell RNA sequencing) sampling in human brain slices was used reliably target and analyze individual This characterization elucidated transitions between PVALB SST subclasses, morphological heterogeneity within an abundant type, identified multiple spatially distinct types the primate-specialized double bouquet cells (DBCs), shed light on cellular differences homologous mouse neocortical These results highlight importance multimodal phenotypic for refinement emerging cell type taxonomies understanding conserved specialized properties

Language: Английский

Citations

81

Integrated multimodal cell atlas of Alzheimer’s disease DOI Creative Commons
Mariano I. Gabitto, Kyle J. Travaglini, Victoria M. Rachleff

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 14, 2024

Alzheimer's disease (AD) is the leading cause of dementia in older adults. Although AD progression characterized by stereotyped accumulation proteinopathies, affected cellular populations remain understudied. Here we use multiomics, spatial genomics and reference atlases from BRAIN Initiative to study middle temporal gyrus cell types 84 donors with varying pathologies. This cohort includes 33 male 51 female donors, an average age at time death 88 years. We used quantitative neuropathology place along a pseudoprogression score. Pseudoprogression analysis revealed two phases: early phase slow increase pathology, presence inflammatory microglia, reactive astrocytes, loss somatostatin

Language: Английский

Citations

68

A molecular and cellular perspective on human brain evolution and tempo DOI
Feline W Lindhout, Fenna M. Krienen, Katherine S. Pollard

et al.

Nature, Journal Year: 2024, Volume and Issue: 630(8017), P. 596 - 608

Published: June 19, 2024

Language: Английский

Citations

22

Making Ramón y Cajal proud: Development of cell identity and diversity in the cerebral cortex DOI
Daniela J. Di Bella, Nuria Domıńguez-Iturza, Juliana Brown

et al.

Neuron, Journal Year: 2024, Volume and Issue: 112(13), P. 2091 - 2111

Published: May 15, 2024

Language: Английский

Citations

19

Integrated multimodal cell atlas of Alzheimer’s disease DOI Creative Commons
Mariano I. Gabitto, Kyle J. Travaglini,

Jeannelle Ariza

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: May 23, 2023

Alzheimer's disease (AD) is the most common cause of dementia in older adults. Neuropathological and imaging studies have demonstrated a progressive stereotyped accumulation protein aggregates, but underlying molecular cellular mechanisms driving AD progression vulnerable cell populations affected by remain coarsely understood. The current study harnesses single spatial genomics tools knowledge from BRAIN Initiative Cell Census Network to understand impact on middle temporal gyrus types. We used image-based quantitative neuropathology place 84 donors spanning spectrum pathology along continuous pseudoprogression score multiomic technologies profile nuclei each donor, mapping their transcriptomes, epigenomes, coordinates type reference with unprecedented resolution. Temporal analysis cell-type proportions indicated an early reduction Somatostatin-expressing neuronal subtypes late decrease supragranular intratelencephalic-projecting excitatory Parvalbumin-expressing neurons, increases disease-associated microglial astrocytic states. found complex gene expression differences, ranging global type-specific effects. These effects showed different patterns indicating diverse perturbations as function progression. A subset particularly severe phenotype, which correlated steeper cognitive decline. created freely available public resource explore these data accelerate progress research at SEA-AD.org.

Language: Английский

Citations

32

The coming decade of digital brain research: A vision for neuroscience at the intersection of technology and computing DOI Creative Commons
Katrin Amunts, Markus Axer, Swati Banerjee

et al.

Imaging Neuroscience, Journal Year: 2024, Volume and Issue: 2, P. 1 - 35

Published: April 1, 2024

Abstract In recent years, brain research has indisputably entered a new epoch, driven by substantial methodological advances and digitally enabled data integration modelling at multiple scales—from molecules to the whole brain. Major are emerging intersection of neuroscience with technology computing. This science combines high-quality research, across scales, culture multidisciplinary large-scale collaboration, translation into applications. As pioneered in Europe’s Human Brain Project (HBP), systematic approach will be essential for meeting coming decade’s pressing medical technological challenges. The aims this paper to: develop concept decade digital discuss community large, identify points convergence, derive therefrom scientific common goals; provide framework current future development EBRAINS, infrastructure resulting from HBP’s work; inform engage stakeholders, funding organisations institutions regarding research; address transformational potential comprehensive models artificial intelligence, including machine learning deep learning; outline collaborative that integrates reflection, dialogues, societal engagement on ethical opportunities challenges as part research.

Language: Английский

Citations

17

Layer 1 NDNF interneurons are specialized top-down master regulators of cortical circuits DOI Creative Commons
Jan Hartung, Anna Schroeder,

Rodrigo Alejandro Péréz Vázquez

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(5), P. 114212 - 114212

Published: May 1, 2024

Diverse types of inhibitory interneurons (INs) impart computational power and flexibility to neocortical circuits. Whereas markers for different IN in cortical layers 2-6 (L2-L6) have been instrumental generating a wealth functional insights, only the recent identification selective marker (neuron-derived neurotrophic factor [NDNF]) has opened comparable opportunities INs L1 (L1INs). However, at present we know very little about connectivity NDNF L1INs with other types, their input-output conversion, existence potential L1IN subtypes. Here, report pervasive inhibition L2/3 (including parvalbumin vasoactive intestinal peptide INs) by L1INs. Intersectional genetics revealed similar physiology subpopulation co-expressing neuropeptide Y. Finally, prominently selectively engage persistent firing, physiological hallmark disconnecting output from current input. Collectively, our work therefore identifies as specialized master regulators superficial neocortex according top-down afferents.

Language: Английский

Citations

15

Layer 1 neocortex: Gating and integrating multidimensional signals DOI Creative Commons
Shuhan Huang, Jingjing Sherry Wu, Giulia Sansone

et al.

Neuron, Journal Year: 2023, Volume and Issue: 112(2), P. 184 - 200

Published: Oct. 31, 2023

Language: Английский

Citations

18

The cell-type underpinnings of the human functional cortical connectome DOI
Xi-Han Zhang,

Kevin M. Anderson,

Hao-Ming Dong

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 21, 2024

Language: Английский

Citations

9

Advances and applications in single-cell and spatial genomics DOI
Jingjing Wang, Fang Ye, Haoxi Chai

et al.

Science China Life Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Language: Английский

Citations

8