microRNA Deficiency in VIP+ Interneurons Leads to Cortical Circuit Dysfunction

Qiu, Fang; Mao, Xingfeng; Liu, Penglai; Wu, Jinyun; Zhang, Yuan; Sun, Daijing; Zhu, Yueyan; Gong, Ling; Shao, Mengmeng; Fan, Keyang; Chen, Junjie; Lu, Juan; Jiang, Yan; Zhang, Yubin; Curia, Giulia; Li, Anan; He, Miao

doi:10.1093/cercor/bhz236

Cited by 18 publications

(23 citation statements)

References 80 publications

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“…Taken together, our observations align with a number of recent reports suggesting that genetic perturbation of VIP+ INs early in development can have significant effects on cortical processing (Batista-Brito et al, 2017;Goff and Goldberg, 2019;Mossner et al, 2020;Qiu et al, 2020). We propose that VIP+ INs represent a core component of early GABAergic networks in S1BF, one that is able to integrate sensory and motor information within the first postnatal week.…”

Section: Discussionsupporting

confidence: 91%

Ontogeny of the VIP+ interneuron sensory-motor circuit prior to active whisking

Vagnoni

Baruchin

Ghezzi

et al. 2020

Preprint

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ABSTRACTDevelopment of the cortical circuits for sensory-motor processing require the coordinated integration of both columnar and long-range synaptic connections. To understand how this occurs at the level of individual neurons we have explored the timeline over which vasoactive intestinal peptide (VIP)-expressing interneurons integrate into mouse somatosensory cortex. We find a distinction in emergent long-range anterior-motor and columnar glutamatergic inputs onto layer (L)2 and L3 VIP+ interneurons respectively. In parallel, VIP+ interneurons form efferent connections onto both pyramidal cells and interneurons in the immediate column in an inside-out manner. Cell-autonomous deletion of the fate-determinant transcription factor, Prox1, spares long-range anterior-motor inputs onto VIP+ interneurons, but leads to deficits in local connectivity. This imbalance in the somatosensory circuit results in altered spontaneous and sensory-evoked cortical activity in vivo. This identifies a critical role for VIP+ interneurons, and more broadly interneuron heterogeneity, in formative circuits of neocortex.

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Section: Discussionsupporting

confidence: 91%

Ontogeny of the VIP+ interneuron sensory-motor circuit prior to active whisking

Vagnoni

Baruchin

Ghezzi

et al. 2020

Preprint

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“…VIP interneurons with postmitotic DICER ablation initially followed a normal developmental trajectory but exhibited progressive cell death in adulthood. Mature VIP interneurons also showed altered electrophysiological characteristics and deficits in synaptic inputs, leading to increased PN excitability and overall cortical activity ( Qiu et al, 2020 ). These findings suggest that miRNAs are indispensable for maintaining the normal function of VIP interneurons, which have far-reaching effects on cortical circuit development and overall network function.…”

Section: Morphology and Functional Connectivitymentioning

confidence: 99%

“…miRNA ablation in cerebellar Purkinje cells eventually leads to cell death following morphological degeneration ( Schaefer et al, 2007 ), and MGE-derived GABAergic interneurons also show increased apoptosis after DICER knockout ( Tuncdemir et al, 2015 ). A specific subtype of interneurons, VIP interneurons were also found to exhibit progressive cell death with postmitotic DICER knockout ( Qiu et al, 2020 ).…”

Section: Cell Maintenance and Survivalmentioning

confidence: 99%

MicroRNAs Instruct and Maintain Cell Type Diversity in the Nervous System

Zolboot

Zampa

et al. 2021

Front. Mol. Neurosci.

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Characterizing the diverse cell types that make up the nervous system is essential for understanding how the nervous system is structured and ultimately how it functions. The astonishing range of cellular diversity found in the nervous system emerges from a small pool of neural progenitor cells. These progenitors and their neuronal progeny proceed through sequential gene expression programs to produce different cell lineages and acquire distinct cell fates. These gene expression programs must be tightly regulated in order for the cells to achieve and maintain the proper differentiated state, remain functional throughout life, and avoid cell death. Disruption of developmental programs is associated with a wide range of abnormalities in brain structure and function, further indicating that elucidating their contribution to cellular diversity will be key to understanding brain health. A growing body of evidence suggests that tight regulation of developmental genes requires post-transcriptional regulation of the transcriptome by microRNAs (miRNAs). miRNAs are small non-coding RNAs that function by binding to mRNA targets containing complementary sequences and repressing their translation into protein, thereby providing a layer of precise spatial and temporal control over gene expression. Moreover, the expression profiles and targets of miRNAs show great specificity for distinct cell types, brain regions and developmental stages, suggesting that they are an important parameter of cell type identity. Here, we provide an overview of miRNAs that are critically involved in establishing neural cell identities, focusing on how miRNA-mediated regulation of gene expression modulates neural progenitor expansion, cell fate determination, cell migration, neuronal and glial subtype specification, and finally cell maintenance and survival.

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“…VIP interneurons have recently attracted much attention as a crucial regulator of cortical circuits (Kim et al, 2017;Wall et al, 2016;Qiu et al, 2019). Unlike PV and SST interneurons, which directly innervate and inhibit pyramidal neurons, VIP interneurons in cortical circuits preferentially target other interneurons, leading to disinhibition of pyramidal neurons (Karnani et al, 2016;Pfeffer et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

microRNA Deficiency in VIP+ Interneurons Leads to Cortical Circuit Dysfunction

Cited by 18 publications

References 80 publications

Ontogeny of the VIP+ interneuron sensory-motor circuit prior to active whisking

Ontogeny of the VIP+ interneuron sensory-motor circuit prior to active whisking

MicroRNAs Instruct and Maintain Cell Type Diversity in the Nervous System

VIP interneurons regulate olfactory bulb output and contribute to odor detection and discrimination

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