Npas4 Regulates Excitatory-Inhibitory Balance within Neural Circuits through Cell-Type-Specific Gene Programs

Cell, Journal Year: 2014, Volume and Issue: 157(5), P. 1216 - 1229

Published: May 1, 2014

Language: Английский

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Transcriptional co-regulation of neuronal migration and laminar identity in the neocortex

Development, Journal Year: 2012, Volume and Issue: 139(9), P. 1535 - 1546

Published: April 3, 2012

The cerebral neocortex is segregated into six horizontal layers, each containing unique populations of molecularly and functionally distinct excitatory projection (pyramidal) neurons inhibitory interneurons. Development the requires orchestrated execution a series crucial processes, including migration young appropriate positions within nascent neocortex, acquisition layer-specific neuronal identities axonal projections. Here, we discuss emerging evidence supporting notion that final laminar positioning cortical are also co-regulated by cell type- transcription factors play concomitant roles in determining molecular identity connectivity these neurons. These transcriptional programs thus provide direct links between mechanisms controlling position

Language: Английский

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Genetic and activity-dependent mechanisms underlying interneuron diversity

Nature reviews. Neuroscience, Journal Year: 2017, Volume and Issue: 18(5), P. 299 - 309

Published: April 6, 2017

Language: Английский

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Neuronal activity is required for the development of specific cortical interneuron subtypes

Nature, Journal Year: 2011, Volume and Issue: 472(7343), P. 351 - 355

Published: April 1, 2011

Language: Английский

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Pyramidal cell regulation of interneuron survival sculpts cortical networks

Nature, Journal Year: 2018, Volume and Issue: 557(7707), P. 668 - 673

Published: May 1, 2018

Language: Английский

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Early emergence of cortical interneuron diversity in the mouse embryo

Science, Journal Year: 2018, Volume and Issue: 360(6384), P. 81 - 85

Published: Feb. 22, 2018

GABAergic interneurons (GABA, γ-aminobutyric acid) regulate neural-circuit activity in the mammalian cerebral cortex. These cortical are structurally and functionally diverse. Here, we use single-cell transcriptomics to study origins of this diversity mouse. We identify distinct types progenitor cells newborn neurons ganglionic eminences, embryonic proliferative regions that give rise interneurons. precursors show temporally spatially restricted transcriptional patterns lead different classes adult Our findings suggest shortly after become postmitotic, their is already patent diverse programs, which subsequently guide further differentiation developing

Language: Английский

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Spatial transcriptomic survey of human embryonic cerebral cortex by single-cell RNA-seq analysis

Cell Research, Journal Year: 2018, Volume and Issue: 28(7), P. 730 - 745

Published: June 4, 2018

The cellular complexity of human brain development has been intensively investigated, although a regional characterization the entire cerebral cortex based on single-cell transcriptome analysis not reported. Here, we performed RNA-seq over 4,000 individual cells from 22 regions mid-gestation embryos. We identified 29 cell sub-clusters, which showed different proportions in each region and pons especially high percentage astrocytes. Embryonic neurons were as diverse adult neurons, they possessed important features their destinies adults. Neuron was unsynchronized cortex, dorsal appeared to be more mature than ventral at this stage. Region-specific genes comprehensively neuronal sub-cluster, large proportion these neural disease related. Our results present systematic landscape regionalized gene expression neuron maturation cortex.

Language: Английский

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Early Somatostatin Interneuron Connectivity Mediates the Maturation of Deep Layer Cortical Circuits

Neuron, Journal Year: 2016, Volume and Issue: 89(3), P. 521 - 535

Published: Feb. 1, 2016

Language: Английский

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Current view on the functional regulation of the neuronal K+-Cl− cotransporter KCC2

Frontiers in Cellular Neuroscience, Journal Year: 2014, Volume and Issue: 8

Published: Jan. 1, 2014

In the mammalian central nervous system, inhibitory strength of chloride (Cl-)-permeable GABAA and glycine receptors (GABAAR GlyR) depends on intracellular Cl- concentration ([Cl-]i). Lowering [Cl-]i enhances inhibition, whereas raising facilitates neuronal activity. A neuron’s basal level [Cl-]i, as well its extrusion capacity, is critically dependent activity electroneutral K+-Cl- cotransporter KCC2, a member SLC12 cation-Cl- (CCC) family. KCC2 deficiency compromises migration, formation maturation GABAergic glutamatergic synaptic connections, results in network hyperexcitability seizure Several neurological disorders including multiple epilepsy subtypes, neuropathic pain, schizophrenia, various insults such trauma ischemia, are associated with significant decreases capacity that result increases subsequent networks. Accordingly, identifying key upstream molecular mediators governing functional regulation modifying these signalling pathways small molecules, might constitute novel neurotherapeutic strategy for diseases. Here, we discuss recent advances understanding mechanisms regulating activity, role play homeostasis neurotransmission. As mediates transport, experimental recording constitutes an important research challenge; therefore also, provide overview different methodological approaches utilized to monitor function both physiological pathological conditions.

Language: Английский

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The Timing of the Excitatory-to-Inhibitory GABA Switch Is Regulated by the Oxytocin Receptor via KCC2

Cell Reports, Journal Year: 2016, Volume and Issue: 15(1), P. 96 - 103

Published: March 24, 2016

Highlights•Oxtr is necessary for the correct timing of GABA switch in developing neurons•Oxtr modulates by directly regulating Cl− transporter KCC2•OXT actions on KCC2 are restricted to an early and narrow time window•Oxtr deficit causes long-lasting defects excitation/inhibition balance neuronsSummaryOxytocin its receptor (Oxtr) play a crucial role postnatal transition neuronal neurotransmission from excitatory inhibitory, developmental process known as switch. Using hippocampal neurons Oxtr-null mice, we show that (1) Oxtr upregulating activity chloride cotransporter KCC2, (2) Oxtr, very window, functional promoting phosphorylation insertion/stabilization at surface, (3) absence electrophysiological alterations recorded mature neurons, finding consistent with reduced level increased susceptibility seizures observed adult mice. These data identify key target oxytocin events may be linked pathogenesis neurodevelopmental disorders.Graphical abstract

Language: Английский

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