GABAergic interneurons form transient layer-specific circuits in early postnatal neocortex

Anastasiades, Paul G.; Marques-Smith, André; Lyngholm, Daniel; Lickiss, Tom; Raffiq, Sayda; Kätzel, Dennis; Miesenböck, Gero; Butt, Simon J. B.

doi:10.1038/ncomms10584

Cited by 72 publications

(85 citation statements)

References 58 publications

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“…Though the majority of cortical interneurons express SCN1A /Na V 1.1 at the AIS (46, 47), with loss of function resulting in Dravet Syndrome with EE (48), somatostatin positive interneurons, which play a role in cortical circuit maturation (49, 50), express a mix of both Na V 1.1 and 1.2 in the proximal AIS (9). Further, Na V 1.2 channels are expressed throughout cerebellar granule cell axons (8), potentially contributing to episodic ataxia (25).…”

Section: Discussionmentioning

confidence: 99%

Opposing Effects on Na V 1.2 Function Underlie Differences Between SCN2A Variants Observed in Individuals With Autism Spectrum Disorder or Infantile Seizures

Ben-Shalom

Keeshen²,

Berríos

et al. 2017

Biological Psychiatry

236

313

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BACKGROUND Variants in SCN2A that disrupt the encoded neuronal sodium channel NaV1.2 are important risk factors for autism spectrum disorder (ASD), developmental delay, and infantile seizures. Variants observed in infantile seizures are predominantly missense, leading to a gain of function and increased neuronal excitability. How variants associated with ASD affect NaV1.2 function and neuronal excitability are unclear. METHODS We examined the properties of 11 ASD-associated SCN2A variants in heterologous expression systems using whole-cell voltage-clamp electrophysiology and immunohistochemistry. Resultant data were incorporated into computational models of developing and mature cortical pyramidal cells that express NaV1.2. RESULTS In contrast to gain of function variants that contribute to seizure, we found that all ASD-associated variants dampened or eliminated channel function. Incorporating these electrophysiological results into a compartmental model of developing excitatory neurons demonstrated that all ASD variants, regardless of their mechanism of action, resulted in deficits in neuronal excitability. Corresponding analysis of mature neurons predicted minimal change in neuronal excitability. CONCLUSIONS This functional characterization thus identifies SCN2A mutation and NaV1.2 dysfunction as the most frequently observed ASD risk factor detectable by exome sequencing and suggests that associated changes in neuronal excitability, particularly in developing neurons, may contribute to ASD etiology.

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Section: Discussionmentioning

confidence: 99%

Opposing Effects on Na V 1.2 Function Underlie Differences Between SCN2A Variants Observed in Individuals With Autism Spectrum Disorder or Infantile Seizures

Ben-Shalom

Keeshen²,

Berríos

et al. 2017

Biological Psychiatry

236

313

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“…Moreover, the decrease in MGE-derived interneuron populations might disrupt transient translaminar networks 71,72 that modulate subsequent functional maturation of cortical circuits.…”

Section: Discussionmentioning

confidence: 99%

Maternal inflammation has a profound effect on cortical interneuron development in a stage and subtype-specific manner

Vasistha

Pardo-Navarro

Gasthaus

et al. 2018

Preprint

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Severe infections during pregnancy are one of the major risk factors for cognitive brain impairment in offspring. It has been suggested that maternal inflammation leads to dysfunction of cortical GABAergic interneurons that in turn underlies cognitive impairment of the affected offspring.However, the evidence comes largely from studies of adult or mature brain and how impairment of inhibitory circuits arises upon maternal inflammation is unknown. Here we show that maternal inflammation affects multiple steps of cortical GABAergic interneuron development, i.e. proliferation of precursor cells, migration and positioning of neuroblasts as well as neuronal maturation. Importantly, the development of distinct subtypes of cortical GABAergic interneurons was discretely impaired as a result of maternal inflammation. This translated into a reduction in cell numbers, redistribution across cortical regions and layers, changes in morphology and cellular properties. Furthermore, selective vulnerability of GABAergic interneuron subtypes was associated with the stage of brain development. Thus, we propose that maternally-derived insults have developmental stage-dependent effects which contribute to the complex etiology of cognitive impairment in the affected offspring.

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“…Interneurons have been suggested to regulate early organizational activity patterns in the cortex and hippocampus (Allene et al, 2008; Bonifazi et al, 2009; Picardo et al, 2011) and to control the expression of critical period plasticity by excitatory neurons (Takesian and Hensch, 2013). Recent work has further suggested complex developmental interactions between populations of inhibitory interneurons (Anastasiades et al, 2016; Marques-Smith et al, 2016; Tuncdemir et al, 2016). Developmental dysregulation of GABAergic cells is associated with pathophysiology underlying neurodevelopmental disorders including autism and schizophrenia, as well as epilepsy (Rossignol, 2011).…”

Section: Introductionmentioning

confidence: 99%

Developmental Dysfunction of VIP Interneurons Impairs Cortical Circuits

Batista-Brito

Vinck

Ferguson

et al. 2017

Neuron

127

110

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GABAergic interneurons play important roles in cortical circuit development. However, there are multiple populations of interneurons and their respective developmental contributions remain poorly explored. Neuregulin 1 (NRG1) and its interneuron-specific receptor ERBB4 are critical genes for interneuron maturation. Using a conditional ErbB4 deletion, we tested the role of vasoactive intestinal peptide (VIP)-expressing interneurons in the postnatal maturation of cortical circuits in vivo. ErbB4 removal from VIP interneurons during development leads to changes in their activity, along with severe dysregulation of cortical temporal organization and state-dependence. These alterations emerge during adolescence, and mature animals in which VIP interneurons lack ErbB4 exhibit reduced cortical responses to sensory stimuli and impaired sensory learning. Our data support a key role for VIP interneurons in cortical circuit development and suggest a possible contribution to pathophysiology in neurodevelopmental disorders. These findings provide a new perspective on the role of GABAergic interneuron diversity in cortical development.

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GABAergic interneurons form transient layer-specific circuits in early postnatal neocortex

Cited by 72 publications

References 58 publications

Opposing Effects on Na V 1.2 Function Underlie Differences Between SCN2A Variants Observed in Individuals With Autism Spectrum Disorder or Infantile Seizures

Opposing Effects on Na V 1.2 Function Underlie Differences Between SCN2A Variants Observed in Individuals With Autism Spectrum Disorder or Infantile Seizures

Maternal inflammation has a profound effect on cortical interneuron development in a stage and subtype-specific manner

Developmental Dysfunction of VIP Interneurons Impairs Cortical Circuits

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