An increase of inhibition drives the developmental decorrelation of neural activity

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

Published: Aug. 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.

Language: Английский

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Astrocyte-secreted neurocan controls inhibitory synapse formation and function

Neuron, Journal Year: 2024, Volume and Issue: 112(10), P. 1657 - 1675.e10

Published: April 3, 2024

Astrocytes strongly promote the formation and maturation of synapses by secreted proteins. Several astrocyte-secreted synaptogenic proteins controlling excitatory synapse development were identified; however, those that induce inhibitory synaptogenesis remain elusive. Here, we identify neurocan as an protein. After secretion from astrocytes, is cleaved into N- C-terminal fragments. We found these fragments have distinct localizations in extracellular matrix. The fragment localizes to controls cortical function. Neurocan knockout mice lacking whole protein or only its domain reduced numbers Through super-resolution microscopy, vivo proximity labeling TurboID, astrocyte-specific rescue approaches, discovered somatostatin-positive regulates their formation. Together, our results unveil a mechanism through which astrocytes control circuit-specific mammalian brain.

Language: Английский

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Somatostatin interneurons control the timing of developmental desynchronization in cortical networks

Neuron, Journal Year: 2024, Volume and Issue: 112(12), P. 2015 - 2030.e5

Published: April 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.

Language: Английский

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Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development

Stem Cell Reports, Journal Year: 2018, Volume and Issue: 10(4), P. 1222 - 1236

Published: March 22, 2018

Human stem cell-derived models of development and neurodegenerative diseases are challenged by cellular immaturity in vitro. Microengineered organ-on-chip (or Organ-Chip) systems designed to emulate microvolume cytoarchitecture enable co-culture distinct cell types. Brain microvascular endothelial cells (BMECs) share common signaling pathways with neurons early development, but their contribution human neuronal maturation is largely unknown. To study this interaction influence microculture, we derived both spinal motor BMECs from induced pluripotent observed increased calcium transient function Chip-specific gene expression Organ-Chips compared 96-well plates. Seeding the Organ-Chip led vascular-neural specific activation that further enhanced vivo-like signatures. The results show vascular system has effects on cord neural tissue, use can move closer an vivo condition.

Language: Английский

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A Transient Translaminar GABAergic Interneuron Circuit Connects Thalamocortical Recipient Layers in Neonatal Somatosensory Cortex

Neuron, Journal Year: 2016, Volume and Issue: 89(3), P. 536 - 549

Published: Feb. 1, 2016

GABAergic activity is thought to influence developing neocortical sensory circuits. Yet the late postnatal maturation of local layer (L)4 circuits suggests alternate sources control in nascent thalamocortical networks. We show that a population L5b, somatostatin (SST)-positive interneuron receives early thalamic synaptic input and, using laser-scanning photostimulation, identify an transient circuit between these cells and L4 spiny stellates (SSNs) disappears by end critical period. Sensory perturbation disrupts transition circuit, suggesting link translaminar SSNs. Conditional silencing SST+ interneurons or conversely biasing toward inhibition overexpression neuregulin-1 type 1 results absence L5b mutants delayed innervation These data role for SSNs neocortex.

Language: Английский

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Developmental Dysfunction of VIP Interneurons Impairs Cortical Circuits

Neuron, Journal Year: 2017, Volume and Issue: 95(4), P. 884 - 895.e9

Published: Aug. 1, 2017

Language: Английский

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Inhibitory Circuits in Cortical Layer 5

Frontiers in Neural Circuits, Journal Year: 2016, Volume and Issue: 10

Published: May 6, 2016

Inhibitory neurons play a fundamental role in cortical computation and behavior. Recent technological advances, such as two photon imaging, targeted vivo recording, molecular profiling, have improved our understanding of the function diversity interneurons, but for technical reasons most work has been directed towards inhibitory superficial layers. Here we review current knowledge specifically on layer 5 microcircuits, which critical controlling output. We focus recent from well-studied rodent barrel cortex, also draw evidence studies primary visual cortex other areas. The both deep their pyramidal cell targets make this challenging essential area study sensory processing.

Language: Английский

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Somatostatin and Somatostatin-Containing Neurons in Shaping Neuronal Activity and Plasticity

Frontiers in Neural Circuits, Journal Year: 2016, Volume and Issue: 10

Published: June 30, 2016

Since its discovery over four decades ago, somatostatin receives growing scientific and clinical interest. Being localized in the nervous system a subset of interneurons acts as neurotransmitter or neuromodulator role fine-tuning neuronal activity involvement synaptic plasticity memory formation are widely recognized recent literature. Combining transgenic animals with electrophysiological, anatomical molecular methods allowed to characterize several subpopulations somatostatin-containing possessing specific physiological features engaged controlling output cortical excitatory neurons. Special characteristic connectivity neurons set them up significant players shaping system. However, is not just marker particular interneuronal subpopulation. Somatostatin itself pre- postsynaptically, modulating excitability responses. In present review we combine knowledge regarding interneurons, trying incorporate it into current view concerning somatostatinergic plasticity.

Language: Английский

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Myelination of parvalbumin interneurons shapes the function of cortical sensory inhibitory circuits

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Oct. 13, 2020

Abstract Myelination of projection neurons by oligodendrocytes is key to optimize action potential conduction over long distances. However, a large fraction myelin enwraps the axons parvalbumin-positive fast-spiking interneurons (FSI), exclusively involved in local cortical circuits. Whether FSI myelination contributes fine‐tuning intracortical networks unknown. Here we demonstrate that required for establishment and maintenance powerful FSI-mediated feedforward inhibition sensory The disruption GABAergic synaptic signaling oligodendrocyte precursor cells prior onset resulted severe defects characterized longer internodes nodes, aberrant branch points proximal axon malformation. Consequently, high-frequency discharges as well FSI-dependent postsynaptic latencies strengths excitatory were reduced. These dysfunctions generated strong excitation-inhibition imbalance correlated with whisker-dependent texture discrimination impairments. therefore critical function mature inhibitory

Language: Английский

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Layer-specific optogenetic activation of pyramidal neurons causes beta–gamma entrainment of neonatal networks

Nature Communications, Journal Year: 2017, Volume and Issue: 8(1)

Published: Feb. 20, 2017

Abstract Coordinated activity patterns in the developing brain may contribute to wiring of neuronal circuits underlying future behavioural requirements. However, causal evidence for this hypothesis has been difficult obtain owing absence tools selective manipulation oscillations during early development. We established a protocol that combines optogenetics with electrophysiological recordings from neonatal mice vivo elucidate substrate network prefrontal cortex. show light-induced activation layer II/III pyramidal neurons are transfected by utero electroporation high-efficiency channelrhodopsin drives frequency-specific spiking and boosts within beta–gamma frequency range. By contrast, V/VI causes nonspecific activation. Thus, entrainment networks fast rhythms relies on neurons. This approach used here be useful further interrogation circuits, their readout.

Language: Английский

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