Development, Diversity, and Death of MGE-Derived Cortical Interneurons

Williams, Rhîannan H.; Riedemann, Therese

doi:10.3390/ijms22179297

Cited by 17 publications

(21 citation statements)

References 267 publications

(341 reference statements)

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“…Though INs comprise only ∼20% of cortical neurons, they are the only GABAergic neurons in cortex, and are critical to regulating activity of cortical circuits through a variety of mechanisms ( Takada et al, 2014 ). This diversity of inhibitory signaling is mediated by a number of functionally distinct subtypes, such as parvalbumin (PV) and somatostatin (SST) INs, which have different birth origins ( Wonders and Anderson, 2006 ; Lim et al, 2018 ) and properties at maturity ( Markram et al, 2004 ; Kepecs and Fishell, 2014 ; Williams and Riedemann, 2021 ). Deficits in IN development and function underlie neurologic and psychiatric disorders, such as epilepsy ( Bozzi et al, 2012 ; Righes Marafiga et al, 2021 ), schizophrenia, bipolar disorder, and autism spectrum disorders ( Rossignol, 2011 ; Marin, 2012 ; Ruden et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Loss of KCC2 in GABAergic Neurons Causes Seizures and an Imbalance of Cortical Interneurons

Zavalin

Hassan

et al. 2022

Front. Mol. Neurosci.

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K-Cl transporter KCC2 is an important regulator of neuronal development and neuronal function at maturity. Through its canonical transporter role, KCC2 maintains inhibitory responses mediated by γ-aminobutyric acid (GABA) type A receptors. During development, late onset of KCC2 transporter activity defines the period when depolarizing GABAergic signals promote a wealth of developmental processes. In addition to its transporter function, KCC2 directly interacts with a number of proteins to regulate dendritic spine formation, cell survival, synaptic plasticity, neuronal excitability, and other processes. Either overexpression or loss of KCC2 can lead to abnormal circuit formation, seizures, or even perinatal death. GABA has been reported to be especially important for driving migration and development of cortical interneurons (IN), and we hypothesized that properly timed onset of KCC2 expression is vital to this process. To test this hypothesis, we created a mouse with conditional knockout of KCC2 in Dlx5-lineage neurons (Dlx5 KCC2 cKO), which targets INs and other post-mitotic GABAergic neurons in the forebrain starting during embryonic development. While KCC2 was first expressed in the INs of layer 5 cortex, perinatal IN migrations and laminar localization appeared to be unaffected by the loss of KCC2. Nonetheless, the mice had early seizures, failure to thrive, and premature death in the second and third weeks of life. At this age, we found an underlying change in IN distribution, including an excess number of somatostatin neurons in layer 5 and a decrease in parvalbumin-expressing neurons in layer 2/3 and layer 6. Our research suggests that while KCC2 expression may not be entirely necessary for early IN migration, loss of KCC2 causes an imbalance in cortical interneuron subtypes, seizures, and early death. More work will be needed to define the specific cellular basis for these findings, including whether they are due to abnormal circuit formation versus the sequela of defective IN inhibition.

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Section: Introductionmentioning

confidence: 99%

Loss of KCC2 in GABAergic Neurons Causes Seizures and an Imbalance of Cortical Interneurons

Zavalin

Hassan

et al. 2022

Front. Mol. Neurosci.

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“…Most cortical and hippocampal interneurons in mammals are derived from three different regions in the basal telencephalon: the MGE, CGE, and preoptic area ( Christodoulou et al, 2021 ). Approximately 60% of cortical interneurons are derived from the MGE, 30% from the CGE, and the remaining 10% from the preoptic area ( Williams and Riedemann, 2021 ). Inhibitory interneurons play a dominant role in maintaining the functional balance of neural circuits (as elaborated in the next section).…”

Section: Medial Ganglionic Eminence-derived Interneuronsmentioning

confidence: 99%

“…The balance between excitation and inhibition in the cortical neural circuits is maintained by GABAergic interneurons ( Wang et al, 2016 ). In animals and humans, interneuron loss or malfunctioning can result in mood disorders, working memory disorders, or cognitive decline ( Casalia et al, 2021 ; Williams and Riedemann, 2021 ), leading to epilepsy ( Knopp et al, 2008 ), Alzheimer’s Disease (AD) ( Fu et al, 2017 ; Najm et al, 2020 ), schizophrenia ( Dienel and Lewis, 2019 ; Van Derveer et al, 2021 ), autism spectrum disorder (ASD) ( Shin et al, 2021 ; Deemyad et al, 2022 ) and other neurological disorders. Researches have revealed that MGE-derived interneuron transplantation offers hope for treating these diseases ( De la Cruz et al, 2011 ; Perez and Lodge, 2013 ; Upadhya et al, 2019 ; Lu et al, 2020 ; Southwell et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Application of Medial Ganglionic Eminence Cell Transplantation in Diseases Associated With Interneuron Disorders

Han

2022

Front. Cell. Neurosci.

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Excitatory projection neurons and inhibitory interneurons primarily accomplish the neural activity of the cerebral cortex, and an imbalance of excitatory-inhibitory neural networks may lead to neuropsychiatric diseases. Gamma-aminobutyric acid (GABA)ergic interneurons mediate inhibition, and the embryonic medial ganglionic eminence (MGE) is a source of GABAergic interneurons. After transplantation, MGE cells migrate to different brain regions, differentiate into multiple subtypes of GABAergic interneurons, integrate into host neural circuits, enhance synaptic inhibition, and have tremendous application value in diseases associated with interneuron disorders. In the current review, we describe the fate of MGE cells derived into specific interneurons and the related diseases caused by interneuron loss or dysfunction and explore the potential of MGE cell transplantation as a cell-based therapy for a variety of interneuron disorder-related diseases, such as epilepsy, schizophrenia, autism spectrum disorder, and Alzheimer’s disease.

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“…Они описаны в неокортексе мышей, крыс, морских свинок, кроликов, кошек и обезьян, в основном вблизи границы между корой и белым веществом, с меньшим количеством в коре, в основном в поверхностных слоях (II-IV) [10,12]. По мнению Williams et al [15][16][17], у крыс эти нейроны в основном обнаруживаются в более глубоких слоях и экспрессируют nNOS на более высоких уровнях. Хотя нейроны nNOS 1-го типа получают множество различных нейромодулирующих сигналов [15,16], почти все они экспрессируют рецептор вещества P, причем как геномные, так и гистологические исследования показали, что это единственная субпопуляция клеток коры головного мозга мышей, которая экспрессируют этот рецептор [3,4,5,13,14].…”

Section: Introductionunclassified

“…По мнению Williams et al [15][16][17], у крыс эти нейроны в основном обнаруживаются в более глубоких слоях и экспрессируют nNOS на более высоких уровнях. Хотя нейроны nNOS 1-го типа получают множество различных нейромодулирующих сигналов [15,16], почти все они экспрессируют рецептор вещества P, причем как геномные, так и гистологические исследования показали, что это единственная субпопуляция клеток коры головного мозга мышей, которая экспрессируют этот рецептор [3,4,5,13,14]. Нейроны nNOS-IR 1-го типа имеют протяженные отростки, которые позволяют им влиять на сосудистую сеть.…”

Section: Introductionunclassified

Age specific features of nNOS immunoreactive neurons in rat neocortex

Rumyantseva

Agadzhanova

Варенцов

et al. 2022

Žurnal anatomii i gistopatologii

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The aim of the study was to evaluate the morphological features of nNOS-positive (nNOS-IR) neurons in the dorsolateral cortex of the frontal lobe of the cerebral hemispheres in albino rats during 180 days of postnatal development.Material and methods. The study was performed on 40 outbred white Wistar rats of different ages, from 1 to 180 days. The object of the study was an area of the right cerebral hemisphere on the dorsolateral surface near the frontal pole (neocortex). On paraffin serial sections of the frontal lobe, an immunohistochemical reaction was performed with antibodies to nNOS and a detection system with horseradish peroxidase. Neuronal morphometry was performed by microphotographs using the ImageJ-Fiji (NIH) 1.51h program, measuring the sectional area of the neuron body, the area of the nucleus, the nuclear-cytoplasmic ratio, and the intensity of the reaction.The significance of differences was assessed by paired Student's t-test.Results. It was found that in mature rats in the frontal lobe cortex nNOS-IR was detected in large multi-polar cells with high activity of the enzyme located in the supragranular layers, spindle-shaped cells with long positive processes at the border with the white matter (type 1), and two varieties of low-positive neurons – accumulations in the VI layer and single ones in other layers (type 2). Polymorphism of nNOS-IR neurons manifests from the birth, but it was possible to distinguish all subpopulations only from the 21st day. Each subpopulation is distinguished by its own age dynamics of the studied parameters and the nature of the distribution of positivity. In addition, in 3–7 day old rat pups, numerous small neurons at the border of the cortex and white matter have transient immunoreactivity.Conclusion. Thus, the division of nNOS-IR neurons into two morphological types proposed in the works of predecessors does not correspond to the number of subpopulations that could be described in the dorsolateral region of the prefrontal cortex in rats. This diversity of nNOS-IR neurons is consistent with the numerous functions described for nitric oxide. For an objective characterization of various classes of nNOS-IR cortical interneurons, it is necessary to use additional data obtained from transcriptomic, histological, electrophysiological, and functional experiments, taking into account species, topographic, and age features. Only an extended approach will make it possible to selectively influence different types of cells and reasonably interpret the results of experimental studies.

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Development, Diversity, and Death of MGE-Derived Cortical Interneurons

Cited by 17 publications

References 267 publications

Loss of KCC2 in GABAergic Neurons Causes Seizures and an Imbalance of Cortical Interneurons

Loss of KCC2 in GABAergic Neurons Causes Seizures and an Imbalance of Cortical Interneurons

Application of Medial Ganglionic Eminence Cell Transplantation in Diseases Associated With Interneuron Disorders

Age specific features of nNOS immunoreactive neurons in rat neocortex

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