Specification and Development of GABAergic Interneurons

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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Endocannabinoid system in the neurodevelopment of GABAergic interneurons: implications for neurological and psychiatric disorders

Reviews in the Neurosciences ◽

10.1515/revneuro-2020-0134 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Chang-geng Song ◽

Xin Kang ◽

Fang Yang ◽

Wan-qing Du ◽

Jia-jia Zhang ◽

...

Keyword(s):

Psychiatric Disorders ◽

Endocannabinoid System ◽

Autism Spectrum ◽

Network Activity ◽

Inhibitory Neurons ◽

Gabaergic Interneurons ◽

Neural Stem Progenitor Cells ◽

The Central Nervous System ◽

Interneuron Development

Abstract In mature mammalian brains, the endocannabinoid system (ECS) plays an important role in the regulation of synaptic plasticity and the functioning of neural networks. Besides, the ECS also contributes to the neurodevelopment of the central nervous system. Due to the increase in the medical and recreational use of cannabis, it is inevitable and essential to elaborate the roles of the ECS on neurodevelopment. GABAergic interneurons represent a group of inhibitory neurons that are vital in controlling neural network activity. However, the role of the ECS in the neurodevelopment of GABAergic interneurons remains to be fully elucidated. In this review, we provide a brief introduction of the ECS and interneuron diversity. We focus on the process of interneuron development and the role of ECS in the modulation of interneuron development, from the expansion of the neural stem/progenitor cells to the migration, specification and maturation of interneurons. We further discuss the potential implications of the ECS and interneurons in the pathogenesis of neurological and psychiatric disorders, including epilepsy, schizophrenia, major depressive disorder and autism spectrum disorder.

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Overexpression of neuregulin 1 in GABAergic interneurons results in reversible cortical disinhibition

Nature Communications ◽

10.1038/s41467-020-20552-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yao-Yi Wang ◽

Bing Zhao ◽

Meng-Meng Wu ◽

Xiao-Li Zheng ◽

Longnian Lin ◽

...

Keyword(s):

Neural Network ◽

Intellectual Disabilities ◽

Sodium Channel ◽

Susceptibility Gene ◽

Gabaergic Interneurons ◽

Neuregulin 1 ◽

Neuropsychiatric Diseases ◽

Underlying Mechanisms ◽

Gabaergic Function ◽

Schizophrenia Susceptibility

AbstractCortical disinhibition is a common feature of several neuropsychiatric diseases such as schizophrenia, autism and intellectual disabilities. However, the underlying mechanisms are not fully understood. To mimic increased expression of Nrg1, a schizophrenia susceptibility gene in GABAergic interneurons from patients with schizophrenia, we generated gtoNrg1 mice with overexpression of Nrg1 in GABAergic interneurons. gtoNrg1 mice showed cortical disinhibition at the cellular, synaptic, neural network and behavioral levels. We revealed that the intracellular domain of NRG1 interacts with the cytoplasmic loop 1 of Nav1.1, a sodium channel critical for the excitability of GABAergic interneurons, and inhibits Nav currents. Intriguingly, activation of GABAergic interneurons or restoring NRG1 expression in adulthood could rescue the hyperactivity and impaired social novelty in gtoNrg1 mice. These results identify mechanisms underlying cortical disinhibition related to schizophrenia and raise the possibility that restoration of NRG1 signaling and GABAergic function is beneficial in certain neuropsychiatric disorders.

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Aberrant development of excitatory circuits to inhibitory neurons in the primary visual cortex after neonatal binocular enucleation

Scientific Reports ◽

10.1038/s41598-021-82679-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Rongkang Deng ◽

Joseph P. Y. Kao ◽

Patrick O. Kanold

Keyword(s):

Visual Cortex ◽

Nmda Receptors ◽

Laser Scanning ◽

Inhibitory Neurons ◽

Gabaergic Interneurons ◽

Cortical Circuits ◽

Retinal Input ◽

Layer 4 ◽

Ampa And Nmda Receptors ◽

Laser Scanning Photostimulation

AbstractThe development of GABAergic interneurons is important for the functional maturation of cortical circuits. After migrating into the cortex, GABAergic interneurons start to receive glutamatergic connections from cortical excitatory neurons and thus gradually become integrated into cortical circuits. These glutamatergic connections are mediated by glutamate receptors including AMPA and NMDA receptors and the ratio of AMPA to NMDA receptors decreases during development. Since previous studies have shown that retinal input can regulate the early development of connections along the visual pathway, we investigated if the maturation of glutamatergic inputs to GABAergic interneurons in the visual cortex requires retinal input. We mapped the spatial pattern of glutamatergic connections to layer 4 (L4) GABAergic interneurons in mouse visual cortex at around postnatal day (P) 16 by laser-scanning photostimulation and investigated the effect of binocular enucleations at P1/P2 on these patterns. Gad2-positive interneurons in enucleated animals showed an increased fraction of AMPAR-mediated input from L2/3 and a decreased fraction of input from L5/6. Parvalbumin-expressing (PV) interneurons showed similar changes in relative connectivity. NMDAR-only input was largely unchanged by enucleation. Our results show that retinal input sculpts the integration of interneurons into V1 circuits and suggest that the development of AMPAR- and NMDAR-only connections might be regulated differently.

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