Large-scale death of retinal astrocytes during normal development is non-apoptotic and implemented by microglia DOI Creative Commons
Vanessa M. Puñal, Caitlin E. Paisley, Federica S. Brecha

и другие.

PLoS Biology, Год журнала: 2019, Номер 17(10), С. e3000492 - e3000492

Опубликована: Окт. 18, 2019

Naturally occurring cell death is a fundamental developmental mechanism for regulating numbers and sculpting developing organs. This particularly true in the nervous system, where large of neurons oligodendrocytes are eliminated via apoptosis during normal development. Given profound impact upon these two major populations, it surprising that another type—the astrocyte—has rarely been studied. It presently unclear whether astrocytes subject to significant death, if so, how occurs. Here, we address questions using mouse retinal as our model system. We show total number declines by over 3-fold period spanning postnatal days 5–14. Surprisingly, do not die apoptosis, canonical underlying vast majority death. Instead, find microglia engulf promote their removal. Genetic ablation inhibits astrocyte leading larger population size at end period. However, completely blocked absence microglia, apparently due ability each other. Nevertheless, mice lacking showed anatomical changes network, with functional consequences astrocyte-associated vasculature hemorrhage. These results establish novel modality naturally demonstrate its importance formation integrity gliovascular network.

Язык: Английский

An increase of inhibition drives the developmental decorrelation of neural activity DOI Creative Commons
Mattia Chini, Thomas Pfeffer, Ileana L. Hanganu‐Opatz

и другие.

eLife, Год журнала: 2022, Номер 11

Опубликована: Авг. 17, 2022

Throughout development, the brain transits from early highly synchronous activity patterns to a mature state with sparse and decorrelated neural activity, yet mechanisms underlying this process are poorly understood. The developmental transition has important functional consequences, as latter is thought allow for more efficient storage, retrieval, processing of information. Here, we show that, in mouse medial prefrontal cortex (mPFC), during first two postnatal weeks decorrelates following specific spatial patterns. This accompanied by concomitant tilting excitation-inhibition (E-I) ratio toward inhibition. Using optogenetic manipulations network modeling, that phenomena mechanistically linked, relative increase inhibition drives decorrelation activity. Accordingly, mice mimicking etiology neurodevelopmental disorders, subtle alterations E-I associated impairments correlational structure spike trains. Finally, capitalizing on EEG data newborn babies, an analogous takes place also human brain. Thus, changes control (de)correlation and, these means, its imbalance might contribute pathogenesis disorders.

Язык: Английский

Процитировано

118
Massively parallel in vivo Perturb-seq reveals cell-type-specific transcriptional networks in cortical development DOI Creative Commons

Xinhe Zheng,

Boli Wu,

Yuejia Liu

и другие.

Cell, Год журнала: 2024, Номер 187(13), С. 3236 - 3248.e21

Опубликована: Май 20, 2024

Leveraging AAVs' versatile tropism and labeling capacity, we expanded the scale of in vivo CRISPR screening with single-cell transcriptomic phenotyping across embryonic to adult brains peripheral nervous systems. Through extensive tests 86 vectors AAV serotypes combined a transposon system, substantially amplified efficacy accelerated gene delivery from weeks days. Our proof-of-principle utero screen identified pleiotropic effects Foxg1, highlighting its tight regulation distinct networks essential for cell fate specification Layer 6 corticothalamic neurons. Notably, our platform can label >6% cerebral cells, surpassing current state-of-the-art at <0.1% by lentivirus, achieve analysis over 30,000 cells one experiment enable massively parallel Perturb-seq. Compatible various phenotypic measurements (single-cell or spatial multi-omics), it presents flexible approach interrogate function types vivo, translating variants their causal function.

Язык: Английский

Процитировано

27
Somatostatin interneurons control the timing of developmental desynchronization in cortical networks DOI Creative Commons
Laura Mòdol, Monika Moissidis, Martijn Selten

и другие.

Neuron, Год журнала: 2024, Номер 112(12), С. 2015 - 2030.e5

Опубликована: Апрель 9, 2024

Synchronous neuronal activity is a hallmark of the developing brain. In mouse cerebral cortex, decorrelates during second week postnatal development, progressively acquiring characteristic sparse pattern underlying integration sensory information. The maturation inhibition seems critical for this process, but interneurons involved in crucial transition network cortex remain unknown. Using vivo longitudinal two-photon calcium imaging period that precedes change from highly synchronous to decorrelated activity, we identify somatostatin-expressing (SST+) as modulators switch mice. Modulation SST+ cells accelerates or delays decorrelation cortical process involves regulating parvalbumin-expressing (PV+) interneurons. critically link inputs with local circuits, controlling neural dynamics while modulating other into nascent circuits.

Язык: Английский

Процитировано

20
Developmental Cell Death in the Cerebral Cortex DOI
Fong Kuan Wong, Oscar Marı́n

Annual Review of Cell and Developmental Biology, Год журнала: 2019, Номер 35(1), С. 523 - 542

Опубликована: Июль 8, 2019

In spite of the high metabolic cost cellular production, brain contains only a fraction neurons generated during embryonic development. rodent cerebral cortex, first wave programmed cell death surges at stages and affects primarily progenitor cells. A second, larger unfolds early postnatal development ultimately determines final number cortical neurons. Programmed in developing cortex is particularly dependent on neuronal activity cell-specific manner with precise temporal control. Pyramidal cells interneurons adjust their numbers sync, which likely crucial for establishment balanced networks excitatory inhibitory contrast, several other populations are almost completely eliminated through apoptosis two weeks development, highlighting importance sculpting mature cortex.

Язык: Английский

Процитировано

113
Cell migration promotes dynamic cellular interactions to control cerebral cortex morphogenesis DOI
Carla G. Silva, Elise Peyre, Laurent Nguyen

и другие.

Nature reviews. Neuroscience, Год журнала: 2019, Номер 20(6), С. 318 - 329

Опубликована: Март 15, 2019

Язык: Английский

Процитировано

104
A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture DOI Creative Commons
Alfredo Llorca, Gabriele Ciceri, Robert Beattie

и другие.

eLife, Год журнала: 2019, Номер 8

Опубликована: Ноя. 18, 2019

The cerebral cortex contains multiple areas with distinctive cytoarchitectonic patterns, but the cellular mechanisms underlying emergence of this diversity remain unclear. Here, we have investigated neuronal output individual progenitor cells in developing mouse neocortex using a combination methods that together circumvent biases and limitations approaches. Our experimental results indicate generate pyramidal cell lineages wide range sizes laminar configurations. Mathematical modeling indicates these outcomes are compatible stochastic model cortical neurogenesis which undergo series probabilistic decisions lead to specification very heterogeneous progenies. findings support mechanism for whose flexibility would make it capable diverse cytoarchitectures characterize distinct neocortical areas.

Язык: Английский

Процитировано

104
Fast, cell-resolution, contiguous-wide two-photon imaging to reveal functional network architectures across multi-modal cortical areas DOI Creative Commons

Keisuke Ota,

Yasuhiro Oisi, Takayuki Suzuki

и другие.

Neuron, Год журнала: 2021, Номер 109(11), С. 1810 - 1824.e9

Опубликована: Апрель 20, 2021

Язык: Английский

Процитировано

104
Deletion of Autism Risk Gene Shank3 Disrupts Prefrontal Connectivity DOI Open Access
Marco Pagani, Alice Bertero, Adam Liska

и другие.

Journal of Neuroscience, Год журнала: 2019, Номер 39(27), С. 5299 - 5310

Опубликована: Май 6, 2019

Mutations in the synaptic scaffolding protein SHANK3 are a major cause of autism and associated with prominent intellectual language deficits. However, neural mechanisms whereby deficiency affects higher-order socio-communicative functions remain unclear. Using high-resolution functional structural MRI adult male mice, here we show that loss Shank3 (Shank3B−/−) results disrupted local long-range prefrontal frontostriatal connectivity. We document hypoconnectivity is reduced short-range cortical projections density, gray matter volume. Finally, disconnectivity predictive social communication deficits, as assessed ultrasound vocalization recordings. Collectively, our reveal critical role development anatomy function, suggest may predispose to disability impairments via dysregulation SIGNIFICANCE STATEMENT commonly autism, intellectual, Previous research has linked basal ganglia dysfunction, motor stereotypies, mechanism gene mutations connectivity Here mice largely abnormal areas. also disruption tightly Our findings orchestrator frontocortical areas underpin observed mutation carriers.

Язык: Английский

Процитировано

103
Shifting Developmental Trajectories During Critical Periods of Brain Formation DOI Creative Commons
Nathalie Dehorter, Isabel del Pino

Frontiers in Cellular Neuroscience, Год журнала: 2020, Номер 14

Опубликована: Сен. 10, 2020

Research on critical periods of brain development is greatly expanding our understanding the cellular and molecular mechanisms underlying epochs heightened plasticity driven by environmental influence. Novel studies have started to reveal that timely interventions during hold potential reorient abnormal developmental trajectories in animal models neurological neuropsychiatric disorders. In this review, we re-examine fundamental criteria characterize a period, highlighting recently discovered health disease. addition, touch upon technological improvements modelling human-derived neural networks vitro. These scientific advances associated with use manipulations immature represent promising new preclinical setting will allow future translatability into clinical applications for neurodevelopmental disorders such as intellectual disability, autism spectrum schizophrenia.

Язык: Английский

Процитировано

103
Activity-Dependent Plasticity of Axo-axonic Synapses at the Axon Initial Segment DOI Creative Commons
Alejandro Pan-Vazquez, Winnie Wefelmeyer, Victoria Gonzalez Sabater

и другие.

Neuron, Год журнала: 2020, Номер 106(2), С. 265 - 276.e6

Опубликована: Фев. 27, 2020

The activity-dependent rules that govern the wiring of GABAergic interneurons are not well understood. Chandelier cells (ChCs) a type interneuron control pyramidal cell output through axo-axonic synapses target axon initial segment. In vivo imaging ChCs during development uncovered narrow window (P12–P18) over which axons arborized and formed connections. We found increases in activity either or individual this temporal result reversible decrease Voltage transmission at segment (AIS) showed were depolarizing period. Identical manipulations network older mice (P40–P46), when ChC inhibitory, resulted instead an increase synapses. propose direction synaptic plasticity follows homeostatic depend on polarity

Язык: Английский

Процитировано

95