A deep learning framework for automated and generalized synaptic event analysis DOI Creative Commons
Philipp S O’Neill, Martıń Baccino-Calace, Peter Rupprecht

и другие.

eLife, Год журнала: 2025, Номер 13

Опубликована: Март 5, 2025

Quantitative information about synaptic transmission is key to our understanding of neural function. Spontaneously occurring events carry fundamental function and plasticity. However, their stochastic nature low signal-to-noise ratio present major challenges for the reliable consistent analysis. Here, we introduce miniML, a supervised deep learning-based method accurate classification automated detection spontaneous events. Comparative analysis using simulated ground-truth data shows that miniML outperforms existing event methods in terms both precision recall. enables precise quantification electrophysiological recordings. We demonstrate learning approach generalizes easily diverse preparations, different optical recording techniques, across animal species. provides not only comprehensive robust framework automated, reliable, standardized events, but also opens new avenues high-throughput investigations dysfunction.

Язык: Английский

Developmental mechanisms underlying the evolution of human cortical circuits DOI
Pierre Vanderhaeghen, Franck Polleux

Nature reviews. Neuroscience, Год журнала: 2023, Номер 24(4), С. 213 - 232

Опубликована: Фев. 15, 2023

Язык: Английский

Процитировано

98

Evolution of cortical neurons supporting human cognition DOI Creative Commons
Anna A. Galakhova, Sarah Hunt, René Wilbers

и другие.

Trends in Cognitive Sciences, Год журнала: 2022, Номер 26(11), С. 909 - 922

Опубликована: Сен. 15, 2022

Cortical expansion in humans might be driven by changes neuronal properties and connectivity rather than sheer increase numbers.Recent breakthroughs large-scale transcriptomic analyses of cortical neurons make it now possible to identify the genetic signature neuron types compare across species.Human upper layers contain with large complex dendrites that allow a single human perform computations similar multilayered network.Strong reliable synapses recover quickly from synaptic activity, fast signaling properties, help these efficiently process information.Several features neurons, such as dendritic size complexity also associate cognitive ability individuals, supporting link between function not only but within species. Human abilities are generally thought arise over course brain evolution. In addition increased numbers, this adaptations their local circuits. We review recent findings on distinct structural, functional, organization microstructure. focus supragranular layers, which showed most prominent during evolution, principal cells: pyramidal neurons. argue evolutionary accompany cortex partially underlie interindividual variability abilities. Compared other animals, cognition clearly stands out. Many species can display very intelligent behavior, typically tuned ecological niche. However, brains capable developing unique skills (e.g., sharing storing information through symbolic language), without civilization would possible. For thousands years, one fundamental questions philosophy neuroscience has been biological origin intelligence. What neurobiological principles species? A major development evolution mammalian is immense neocortex [1.DeFelipe J. The brain, nature circuits, intellectual creativity.Front. Neuroanat. 2011; 5: 29Crossref PubMed Scopus (307) Google Scholar]. supports higher functions characterize humans. Relative total size, cerebral largest among mammals, its grey white matter occupies 75–82% entire mass or volume [2.Herculano-Houzel S. remarkable, yet extraordinary, scaled-up primate associated cost.Proc. Natl. Acad. Sci. U. A. 2012; 109: 10661-10668Crossref (363) Scholar] noticeably larger number gyri [3.Fernández V. et al.Cerebral folding: what have we learned?.EMBO 2016; 35: 1021-1044Crossref (210) Larger cortices more thus computational units store information. comparison 75 mammals birds demonstrated avian pallium (see Glossary) correlates measurements [4.Herculano-Houzel Numbers capability.Curr. Opin. Behav. 2017; 16: 1-7Crossref (95) compared primates, both 'remarkable, extraordinary' key puzzle should sought solely overall anatomy. fact, just expected for same Furthermore, frontal often linked advantage (although relatively non-allometrically expanded [5.Preuss T.M. Wise S.P. Evolution prefrontal cortex.Neuropsychopharmacology. 2022; 47: 3-19Crossref (36) Scholar]) disproportionately [6.Semendeferi K. al.Humans great apes share cortex.Nat. Neurosci. 2002; 272-276Crossref (406) Scholar,7.Smaers J.B. al.Exceptional humans.Curr. Biol. 27: 714-720Abstract Full Text PDF (84) Moreover, species, including humans, invariably contains 20–25% all even though relative reach 82% Hence, increases reflect non-neuronal Our activity almost hundred billion connections, form building blocks coding, processing, storage ultimately giving rise cognition. Given astronomic order 1014 1015 Scholar,8.DeFelipe al.Microstructure neocortex: comparative aspects.J. Neurocytol. 31: 299-316Crossref (480) Scholar], slightest efficiency transfer translate into impact power brain. Accelerated took place at scales organization: scale genes [9.Florio M. al.Evolution cell-type specificity human-specific preferentially expressed progenitors fetal neocortex.eLife. 2018; 7e32332Google regulation [10.Bozek al.Organization lipidome revealed analysis human, chimpanzee, macaque, mouse tissues.Neuron. 2015; 85: 695-702Abstract (108) proteins [11.Grant S.G.N. general basis synapse complexes.Cold Spring Harb. Symp. Quant. 2009; 74: 249-257Google lipids influencing how [12.Elston G.N. al.The cell cognition: study monkey.J. 2001; 21: RC163Crossref networks [13.Ardesch D.J. al.Evolutionary multimodal association areas chimpanzees.Proc. 2019; 116: 7101-7106Crossref (71) [14.Changeux J.P. al.A connectomic hypothesis hominization brain.Cereb. Cortex. 2021; 2425-2449Crossref (33) evolve. result multiscale diversity structure connections. Thus, speed accomplish tasks rooted deeper hierarchy characteristics basic elements: [15.Dorus al.Accelerated nervous system Homo sapiens.Cell. 2004; 119: 1027-1040Abstract (344) Scholar, 16.Goriounova N.A. al.Large intelligence.eLife. 7e41714Crossref (63) 17.Lee al.Human vitro systems examining plasticity brain.J. Neurophysiol. 2020; 123: 945-965Crossref (7) 18.Hill R.S. Walsh C.A. Molecular insights evolution.Nature. 2005; 437: 64-67Crossref (163) Do specialized properties? Recent advances single-cell transcriptomics well identification types, physiological, morphological, molecular, us answer question. [19.Berg neocortical involves glutamatergic diversification.Nature. 598: 151-158Crossref (66) 20.Bakken T.E. al.Comparative cellular motor marmoset mouse.Nature. 111-119Crossref (143) 21.Hodge R.D. al.Conserved divergent versus cortex.Nature. 536: 171-178Google By comparing those evolutionarily conserved distinguished review, discuss vantage point attempt put forward may explain observed gap mental provide an overview evidence this. primarily adult abundant type, acknowledge neurotransmitter [22.Berto oligodendrocytes brain.Proc. 24334-24342Crossref (31) Scholar,23.Oberheim al.Astrocytic distinguishes brain.Trends 2006; 29: 547-553Abstract (516) likely contribute developmental timing play important role Although topic falls outside scope like reader excellent reviews [24.Doan R.N. transcriptional regulation: behavior neurological conditions.Annu. Rev. 41: 185-206Crossref (13) 25.Espinós mechanisms regulating neurogenesis.Dev. Neurobiol. 82: 428-453Google 26.Fenlon L.R. Timing mechanism cortex.Brain Evol. 97: 8-32Google Finally, our morpho-electric extensively studied layers. Comparing multiple orders [27.Butti C. cetartiodactyls: I. Golgi morphology bottlenose dolphin (Tursiops truncatus), minke whale (Balaenoptera acutorostrata), humpback (Megaptera novaeangliae).Brain Struct. Funct. 220: 3339-3368Crossref (27) 28.Jacobs B. gigantopyramidal primary mammals.J. Comp. Neurol. 526: 496-536Google 29.Jardim-Messeder D. al.Dogs brain: trade-off body carnivoran species.Front. 11: 118Crossref (54) primates [30.Sherwood C.C. al.Invariant density scaling evolution.Cereb. 30: 5604-5615Crossref reveals does surface gyrencephalization thickness tends while densities decrease Scholar,31.Balaram P. Kaas J.H. Towards unified scheme lamination visual primates: NeuN VGLUT2 immunoreactivity.Front. 2014; 8: 81Crossref (41) Scholar,32.Semendeferi al.Spatial pole sets apart apes.Cereb. 1485-1497Crossref (157) six-layered (Box 1), there substantial variations cytoarchitectonic organization. This variation reflects functional [33.Elston Cortex, cell: new function.Cereb. 2003; 13: 1124-1138Crossref (329) Scholar,34.Elston Specialization evolution.in: Kass Nervous Systems. Elsevier, 2007: 191-242Crossref (94) As sensory flows progressively integrative temporal parietal lobes [35.Maunsell J.H.R. Functional streams.Curr. 1992; 2: 506-510Crossref (81) Scholar,36.Bizley J.K. Cohen Y.E. what, where auditory-object perception.Nat. 2013; 14: 693-707Crossref (269) stimuli combined along way finally create representation. Similarly, laminar follows From areas, gradient increasingly thicker [37.Wagstyl al.Cortical gradients structural hierarchies.Neuroimage. 111: 241-250Crossref (104) (supported mostly 3 (L3) 5 (L5), [38.Wagstyl al.BigBrain 3D atlas layers: diverge cortices.PLoS 18e3000678Crossref (68) Scholar]), arbors [39.Behav evolutions mammals: "over-700-gram club quartet".Brain 68-78Google Scholar,40.Elston Fujita Pyramidal development: postnatal spinogenesis, growth, axon electrophysiology.Front. 78Crossref (102) greater spines contacts [41.Jacobs al.Regional spine cortex: quantitative study.Cereb. 558-571Crossref (343) (Figure 1). particularly pronounced higher-order Scholar,42.Bianchi al.Dendritic chimpanzee regional specializations humans.Cereb. 23: 2429-2436Crossref (98) Even Betz cells cortex, although having soma covering big cats, longest length [20.Bakken Scholar,28.Jacobs Yet, remain constant, resulting highest per Scholar,30.Sherwood Scholar,43.Benavides-Piccione R. area differences morphology.J. 337-346Crossref (138) Scholar].Box 1Cortical neuronsIn arranged Scholar,47.Mohan H. axonal architecture individual neocortex.Cereb. 25: 4839-4853Crossref (116) 2–6 (L2–L6) predominantly (70–80%) projection cortex. They accumulate integrate vast pass locally subcortical excitatory synapses. load transmission lies strongly regulated shaped diverse population inhibitory interneurons [8.DeFelipe Scholar].The broad species: consist pyramidal-shaped gives apical basal dendrites. dendrite orientated towards ends distal tuft, extend radially layers.The stereotypical long tempted neuroscientists derive generalized rules connectivity. L1 mainly axons sparse regulate inputs [101.Genescu Garel Being superficial: viewpoint layer 1 wiring.Curr. 66: 125-134Crossref Based neuroanatomical physiological evidence, L2/L3, recurrent computation happens: L2/L3 many re-excitatory preamplify information, send output L5/L6 [102.Shepherd G.M. microcircuit concept applied evolution: three-layer six-layer cortex.Front. 30Crossref (76) L3 main source feedforward projections receive input superficial deep cells. L5 part direct thalamocortical cortico-cortical microcircuits dictate structures [103.Takahashi N. al.Active currents gate descending outputs 1277-1285Crossref (70) Scholar].Supragranular seem especially Figure 2 text). monkeys progressive shift connections (L5/L6) (L2/L3). proportion originate [44.Goulas mammals.Trends 775-788Abstract These proportionately [46.Hutsler J.J. layering enlargement rodent carnivore species.Brain Res. 1052: 71-81Crossref integration Supragranular Such represent intracortical L2 L3, Scholar,45.Semendeferi al.Prefrontal apes: 10.Am. Phys. Anthropol. 114: 224-241Crossref (493) proportionally thickest (~50%) followed (46%), carnivores (36%), then rodents (19%) suggesting distinctions devoted 2). effects do cells? Neurons connect making dendrites, physical space potential distinctive feature macaque On average, three times [47.Mohan 3, Key figure). Importantly, simp

Язык: Английский

Процитировано

84

Cortical somatostatin interneuron subtypes form cell-type-specific circuits DOI
Jingjing Sherry Wu, Elaine Sevier, Deepanjali Dwivedi

и другие.

Neuron, Год журнала: 2023, Номер 111(17), С. 2675 - 2692.e9

Опубликована: Июнь 29, 2023

Язык: Английский

Процитировано

76

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

и другие.

Nature Neuroscience, Год журнала: 2024, Номер unknown

Опубликована: Окт. 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

Язык: Английский

Процитировано

66

Cell-type-specific inhibitory circuitry from a connectomic census of mouse visual cortex DOI Creative Commons
Casey M Schneider-Mizell, Ágnes L. Bodor, Derrick Brittain

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Янв. 24, 2023

Mammalian cortex features a vast diversity of neuronal cell types, each with characteristic anatomical, molecular and functional properties. Synaptic connectivity powerfully shapes how type participates in the cortical circuit, but mapping rules at resolution distinct types remains difficult. Here, we used millimeter-scale volumetric electron microscopy 1 to investigate all inhibitory neurons across densely-segmented population 1352 cells spanning layers mouse visual cortex, producing wiring diagram connections more than 70,000 synapses. Taking data-driven approach inspired by classical neuroanatomy, classified based on relative targeting dendritic compartments other developed novel classification excitatory morphological synaptic input The between revealed class disinhibitory specialist basket cells, addition familiar subclasses. Analysis onto found widespread specificity, many interneurons exhibiting differential certain subpopulations spatially intermingled potential targets. Inhibitory was organized into “motif groups,” diverse sets that collectively target both perisomatic same Collectively, our analysis identified new organizing principles for inhibition will serve as foundation linking modern multimodal atlases diagram.

Язык: Английский

Процитировано

60

The proteomic landscape of synaptic diversity across brain regions and cell types DOI Creative Commons
Marc van Oostrum, Thomas M. Blok, Stefano L. Giandomenico

и другие.

Cell, Год журнала: 2023, Номер 186(24), С. 5411 - 5427.e23

Опубликована: Ноя. 1, 2023

Neurons build synaptic contacts using different protein combinations that define the specificity, function, and plasticity potential of synapses; however, diversity proteomes remains largely unexplored. We prepared synaptosomes from 7 transgenic mouse lines with fluorescently labeled presynaptic terminals. Combining microdissection 5 brain regions fluorescent-activated synaptosome sorting (FASS), we isolated analyzed 18 synapse types. discovered ∼1,800 unique synapse-type-enriched proteins allocated thousands to types synapses (https://syndive.org/). identify shared modules highlight proteomic hotspots for specialization. reveal common features striatal dopaminergic proteome discover signatures relate functional properties interneuron classes. This study provides a molecular systems-biology analysis framework integrate information subtypes interest cellular or circuit-level experiments.

Язык: Английский

Процитировано

59

A ubiquitous spectrolaminar motif of local field potential power across the primate cortex DOI Creative Commons
Diego Mendoza-Halliday, Alex J. Major,

Noah Lee

и другие.

Nature Neuroscience, Год журнала: 2024, Номер 27(3), С. 547 - 560

Опубликована: Янв. 18, 2024

Abstract The mammalian cerebral cortex is anatomically organized into a six-layer motif. It currently unknown whether corresponding laminar motif of neuronal activity patterns exists across the cortex. Here we report such in power local field potentials (LFPs). Using probes, recorded LFPs from 14 cortical areas hierarchy five macaque monkeys. locations recordings were histologically identified by electrolytic lesions. Across all areas, found ubiquitous spectrolaminar pattern characterized an increasing deep-to-superficial layer gradient high-frequency peaking layers 2/3 and superficial-to-deep alpha-beta 5/6. Laminar additional species showed that highly preserved among primates—macaque, marmoset human—but more dissimilar mouse. Our results suggest existence canonical layer-based frequency-based mechanism for computation.

Язык: Английский

Процитировано

52

The logic of recurrent circuits in the primary visual cortex DOI Creative Commons
Ian Antón Oldenburg, William D. Hendricks, Gregory Handy

и другие.

Nature Neuroscience, Год журнала: 2024, Номер 27(1), С. 137 - 147

Опубликована: Янв. 1, 2024

Abstract Recurrent cortical activity sculpts visual perception by refining, amplifying or suppressing input. However, the rules that govern influence of recurrent remain enigmatic. We used ensemble-specific two-photon optogenetics in mouse cortex to isolate impact from external found spatial arrangement and feature preference stimulated ensemble neighboring neurons jointly determine net effect activity. Photoactivation these ensembles drives suppression all cells beyond 30 µm but uniformly activation closer similarly tuned cells. In nonsimilarly cells, compact, cotuned drive suppression, while diffuse, activation. Computational modeling suggests highly local excitatory connectivity selective convergence onto inhibitory explain effects. Our findings reveal a straightforward logic which space their on

Язык: Английский

Процитировано

37

Whole-cortex in situ sequencing reveals input-dependent area identity DOI Creative Commons
Xiaoyin Chen, Stephan Fischer,

M. Rué

и другие.

Nature, Год журнала: 2024, Номер unknown

Опубликована: Апрель 24, 2024

The cerebral cortex is composed of neuronal types with diverse gene expression that are organized into specialized cortical areas. These areas, each characteristic cytoarchitecture1,2, connectivity3,4 and activity5,6, wired modular networks3,4,7. However, it remains unclear whether these spatial organizations reflected in transcriptomic signatures how such established development. Here we used BARseq, a high-throughput situ sequencing technique, to interrogate the 104 cell-type marker genes 10.3 million cells, including 4,194,658 neurons over nine mouse forebrain hemispheres, at cellular resolution. De novo clustering single revealed consistent previous single-cell RNA studies8,9. composition highly predictive area identity. Moreover, areas similar compositions types, which defined as modules, overlap connected, suggesting same organization both connectivity. To explore profiles depend on development, assessed distributions after neonatal binocular enucleation. Notably, enucleation caused shifting compositional visual towards neighbouring within module, peripheral inputs sharpen distinct identities modules. Enabled by high throughput, low cost reproducibility our study provides proof principle for use large-scale reveal brain-wide molecular architecture understand its

Язык: Английский

Процитировано

24

Inhibitory specificity from a connectomic census of mouse visual cortex DOI Creative Commons
Casey M Schneider-Mizell, Ágnes L. Bodor, Derrick Brittain

и другие.

Nature, Год журнала: 2025, Номер 640(8058), С. 448 - 458

Опубликована: Апрель 9, 2025

Mammalian cortex features a vast diversity of neuronal cell types, each with characteristic anatomical, molecular and functional properties1. Synaptic connectivity shapes how type participates in the cortical circuit, but mapping rules at resolution distinct types remains difficult. Here we used millimetre-scale volumetric electron microscopy2 to investigate all inhibitory neurons across densely segmented population 1,352 cells spanning layers mouse visual cortex, producing wiring diagram inhibition more than 70,000 synapses. Inspired by classical neuroanatomy, classified based on targeting dendritic compartments developed an excitatory neuron classification reconstructions whole-cell maps synaptic input. Single-cell showed class disinhibitory specialist that targets basket cells. Analysis onto found widespread specificity, many interneurons exhibiting differential spatially intermingled subpopulations. Inhibitory was organized into 'motif groups', diverse sets collectively target both perisomatic same targets. Collectively, our analysis identified new organizing principles for will serve as foundation linking contemporary multimodal atlases diagram.

Язык: Английский

Процитировано

8