Early emergence of cortical interneuron diversity in the mouse embryo

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

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Foxg1 Regulates the Postnatal Development of Cortical Interneurons

Cerebral Cortex ◽

10.1093/cercor/bhy051 ◽

2018 ◽

Vol 29 (4) ◽

pp. 1547-1560 ◽

Cited By ~ 12

Author(s):

Wei Shen ◽

Ru Ba ◽

Yan Su ◽

Yang Ni ◽

Dongsheng Chen ◽

...

Keyword(s):

Postnatal Development ◽

Neural Circuit ◽

Neurological Diseases ◽

Cortical Interneuron ◽

Conditional Deletion ◽

Cortical Interneurons ◽

Migration Capacity ◽

Dendritic Complexity ◽

Foxg1 Syndrome

AbstractAbnormalities in cortical interneurons are closely associated with neurological diseases. Most patients with Foxg1 syndrome experience seizures, suggesting a possible role of Foxg1 in the cortical interneuron development. Here, by conditional deletion of Foxg1, which was achieved by crossing Foxg1fl/fl with the Gad2-CreER line, we found the postnatal distributions of somatostatin-, calretinin-, and neuropeptide Y-positive interneurons in the cortex were impaired. Further investigations revealed an enhanced dendritic complexity and decreased migration capacity of Foxg1-deficient interneurons, accompanied by remarkable downregulation of Dlx1 and CXCR4. Overexpression of Dlx1 or knock down its downstream Pak3 rescued the differentiation detects, demonstrated that Foxg1 functioned upstream of Dlx1-Pak3 signal pathway to regulate the postnatal development of cortical interneurons. Due to the imbalanced neural circuit, Foxg1 mutants showed increased seizure susceptibility. These findings will improve our understanding of the postnatal development of interneurons and help to elucidate the mechanisms underlying seizure in patients carrying Foxg1 mutations.

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Implications of Extended Inhibitory Neuron Development

International Journal of Molecular Sciences ◽

10.3390/ijms22105113 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5113

Author(s):

Jae-Yeon Kim ◽

Mercedes F. Paredes

Keyword(s):

Neural Circuit ◽

Inhibitory Neuron ◽

Postnatal Period ◽

Specific Pattern ◽

Inhibitory Neurons ◽

Gabaergic Interneuron ◽

Gabaergic Interneurons ◽

Neuron Development ◽

Cortical Regions ◽

Circuit Formation

A prolonged developmental timeline for GABA (γ-aminobutyric acid)-expressing inhibitory neurons (GABAergic interneurons) is an amplified trait in larger, gyrencephalic animals. In several species, the generation, migration, and maturation of interneurons take place over several months, in some cases persisting after birth. The late integration of GABAergic interneurons occurs in a region-specific pattern, especially during the early postnatal period. These changes can contribute to the formation of functional connectivity and plasticity, especially in the cortical regions responsible for higher cognitive tasks. In this review, we discuss GABAergic interneuron development in the late gestational and postnatal forebrain. We propose the protracted development of interneurons at each stage (neurogenesis, neuronal migration, and network integration), as a mechanism for increased complexity and cognitive flexibility in larger, gyrencephalic brains. This developmental feature of interneurons also provides an avenue for environmental influences to shape neural circuit formation.

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ADENOSINE INHIBITION OF γ-AMINOBUTYRIC ACID RELEASE FROM SLICES OF RAT CEREBRAL CORTEX

British Journal of Pharmacology ◽

10.1111/j.1476-5381.1980.tb10888.x ◽

1980 ◽

Vol 69 (1) ◽

pp. 107-112 ◽

Cited By ~ 136

Author(s):

CAROLYN HOLLINS ◽

TREVOR W. STONE

Keyword(s):

Cerebral Cortex ◽

Aminobutyric Acid ◽

Rat Cerebral Cortex ◽

Acid Release

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Studies on the collectability of3H-γ-aminobutyric acid from rat cerebral cortex; Effects of lithium

Cellular and Molecular Life Sciences ◽

10.1007/bf01926330 ◽

1974 ◽

Vol 30 (5) ◽

pp. 525-526 ◽

Cited By ~ 6

Author(s):

F. V. DeFeudis

Keyword(s):

Cerebral Cortex ◽

Aminobutyric Acid ◽

Rat Cerebral Cortex

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Effect of maternal protein malnutrition on the developing cerebral cortex of mouse embryo: An electron microscopic study

Experimental Neurology ◽

10.1016/0014-4886(80)90081-3 ◽

1980 ◽

Vol 68 (2) ◽

pp. 228-239 ◽

Cited By ~ 5

Author(s):

Tsunekazu Yamano ◽

Morimi Shimada ◽

Syosaku Yamazaki ◽

Masakatsu Goto ◽

Noriaki Ohoya

Keyword(s):

Cerebral Cortex ◽

Microscopic Study ◽

Electron Microscopic Study ◽

Mouse Embryo ◽

Protein Malnutrition ◽

Electron Microscopic

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Effects of calcium on the potassium-stimulated release of radioactive β-alanine and γ-aminobutyric acid from slices of rat cerebral cortex and spinal cord

Brain Research ◽

10.1016/0006-8993(77)90449-8 ◽

1977 ◽

Vol 121 (1) ◽

pp. 179-181 ◽

Cited By ~ 41

Author(s):

G.A.R. Johnston

Keyword(s):

Spinal Cord ◽

Cerebral Cortex ◽

Aminobutyric Acid ◽

Rat Cerebral Cortex

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Semaphorin 3C attracts MGE-derived cortical interneurons in the deep migratory stream guiding them into the developing neocortex

10.1101/2021.03.18.435991 ◽

2021 ◽

Author(s):

Kiara Aiello ◽

Jurgen Bolz

Keyword(s):

Potential Role ◽

Inhibitory Neurons ◽

Semaphorin 3A ◽

Cortical Interneuron ◽

Guidance Cue ◽

Cortical Interneurons ◽

Developing Neocortex ◽

Dorsal Telencephalon ◽

Migratory Stream

While it is known that Semaphorin 3C acts as a guidance cue for axons during brain development, their potential role during interneuron migration is largely unknown. One striking observation is that Sema3C demarcates the pallial/subpallial border and the intracortical pathway of cortical interneurons in the dorsal telencephalon. Moreover, migrating cortical interneurons express Neuropilin1 and Neuropilin2, described receptors for Semaphorin 3A, 3F and 3C. All these reasons prompt us to examine possible roles for Sema3C on cortical interneuron migration. Using several in vitro approaches, we showed that Nrp1-expressing MGE-derived interneurons from the deep migratory stream migrate towards the increasing Sema3C gradients. In contrast, inhibitory neurons from the superficial migratory stream that express Nrp2, do not respond to this guidance cue. In the present study, we proposed that diffusible Sema3C expressed in the Pallium provides a permissive corridor that attracts the Nrp1- expressing interneurons from the DMS into the dorsal telencephalon.

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Perceptual detection depends on spike count integration

10.1101/865410 ◽

2019 ◽

Author(s):

Jackson J. Cone ◽

Morgan L. Bade ◽

Nicolas Y. Masse ◽

Elizabeth A. Page ◽

David J. Freedman ◽

...

Keyword(s):

Neural Networks ◽

Cerebral Cortex ◽

Visual Cortex ◽

Recurrent Neural Networks ◽

Neural Circuit ◽

Visual Detection ◽

Spike Count ◽

Neuronal Responses ◽

Neuronal Populations ◽

And Behavior

AbstractWhenever the retinal image changes some neurons in visual cortex increase their rate of firing, while others decrease their rate of firing. Linking specific sets of neuronal responses with perception and behavior is essential for understanding mechanisms of neural circuit computation. We trained mice to perform visual detection tasks and used optogenetic perturbations to increase or decrease neuronal spiking primary visual cortex (V1). Perceptual reports were always enhanced by increments in V1 spike counts and impaired by decrements, even when increments and decrements were delivered to the same neuronal populations. Moreover, detecting changes in cortical activity depended on spike count integration rather than instantaneous changes in spiking. Recurrent neural networks trained in the task similarly relied on increments in neuronal activity when activity was costly. This work clarifies neuronal decoding strategies employed by cerebral cortex to translate cortical spiking into percepts that can be used to guide behavior.

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Clinically Relevant Concentrations of Propofol but Not Midazolam Alter In Vitro Dendritic Development of Isolated γ-Aminobutyric Acid-positive Interneurons

Anesthesiology ◽

10.1097/00000542-200505000-00016 ◽

2005 ◽

Vol 102 (5) ◽

pp. 970-976 ◽

Cited By ~ 78

Author(s):

Laszlo Vutskits ◽

Eduardo Gascon ◽

Edomer Tassonyi ◽

Jozsef Zoltan Kiss

Keyword(s):

Cell Death ◽

Dendritic Growth ◽

Molecular Mechanisms ◽

Neuronal Development ◽

Nervous System Development ◽

Gabaergic Neurons ◽

Aminobutyric Acid ◽

Gabaergic Interneurons ◽

Short Term Exposure ◽

Dendritic Development

Background Recent laboratory studies showed that exposure to supraclinical concentrations of propofol can induce cell death of immature neurons. However, no data are available regarding the effects of clinically relevant concentrations of this agent on neuronal development. The authors addressed this issue by evaluating the effect of propofol on dendritic growth and arbor expansion of developing gamma-aminobutyric acid-positive (GABAergic) interneurons. Methods Immature neuroblasts were isolated from the newborn rat subventricular zone and differentiated into GABAergic interneurons in culture. In addition to cell death, the effects of increasing concentrations and durations of propofol exposure on neuronal dendritic development were evaluated using the following morphologic parameters: total dendritic length, primary dendrites, branching point, and Scholl analysis. Results The authors demonstrate that propofol induced cell death of GABAergic neurons at concentrations of 50 microg/ml or greater. As little as 1 microg/ml propofol significantly altered several aspects of dendritic development, and as little as 4 h of exposure to this agent resulted in a persistent decrease in dendritic growth. In contrast, application of midazolam did not affect neuronal development. Conclusion Short-term exposure of immature developing GABAergic neurons to clinically relevant concentrations of propofol can induce long-term changes in dendritic arbor development. These results suggest that propofol anesthesia during central nervous system development could interfere with the molecular mechanisms driving the differentiation of GABAergic neurons and thus could potentially lead to impairment of neural networks.

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