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Epidermal growth factor signals attenuate phenotypic and functional development of neocortical GABA neurons.

Journal of neurochemistry | 2017

Phenotypic development of neocortical GABA neurons is highly plastic and promoted by various neurotrophic factors such as neuregulin-1. A subpopulation of GABA neurons expresses not only neuregulin receptor (ErbB4) but also epidermal growth factor (EGF) receptor (ErbB1) during development, but the neurobiological action of EGF on this cell population is less understood than that of neuregulin-1. Here, we examined the effects of exogenous EGF on immature GABA neurons both in culture and in vivo and also explored physiological consequences in adults. We prepared low density cultures from the neocortex of rat embryos and treated neocortical neurons with EGF. EGF decreased protein levels of glutamic acid decarboxylases (GAD65 and GAD67), and EGF influences on neuronal survival and glial proliferation were negligible or limited. The EGF treatment also diminished the frequency of miniature inhibitory postsynaptic currents (mIPSCs). In vivo administration of EGF to mouse pups reproduced the above GABAergic phenomena in neocortical culture. In EGF-injected postnatal mice, GAD- and parvalbumin-immunoreactivities were reduced in the frontal cortex. In addition, postnatal EGF treatment decreased mIPSC frequency in, and the density of, GABAergic terminals on pyramidal cells. Although these phenotypic influences on GABA neurons became less marked during development, it later resulted in the reduced β- and γ-powers of sound-evoked electroencephalogram in adults, which is regulated by parvalbumin-positive GABA neurons and implicated in the schizophrenia pathophysiology. These findings suggest that, in contrast to the ErbB4 ligand of neuregulin-1, the ErbB1 ligand of EGF exerts unique maturation-attenuating influences on developing cortical GABAergic neurons.

Pubmed ID: 28608461 RIS Download

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Goat Anti-Rabbit IgG H&L (Alexa Fluor® 488) (antibody)

RRID:AB_2630356

This polyclonal secondary targets IgG (H+L)

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VGAT (VIAAT, vesicular GABA transporter) antibody (antibody)

RRID:AB_2571622

This polyclonal targets mouse VGAT, 31-112 aa(BC052020)

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Anti-Microtubule-Associated Protein 2 (MAP2) (antibody)

RRID:AB_91939

This polyclonal targets Microtubule-Associated Protein 2 (MAP2)

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Anti-Actin Antibody, clone C4 (antibody)

RRID:AB_2223041

This monoclonal targets actin

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gamma Enolase (NSE-P1) (antibody)

RRID:AB_627513

This monoclonal targets gamma Enolase (NSE-P1)

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Anti-GAD67 (antibody)

RRID:AB_2278725

This monoclonal targets GAD67

View all literature mentions

Anti-Glutamic Acid Decarboxylase 65/67 antibody produced in rabbit (antibody)

RRID:AB_477019

This polyclonal targets Glutamic Acid Decarboxylase 65/67

View all literature mentions

Goat Anti-Rabbit IgG H&L (Alexa Fluor® 488) (antibody)

RRID:AB_2630356

This polyclonal secondary targets IgG (H+L)

View all literature mentions

VGAT (VIAAT, vesicular GABA transporter) antibody (antibody)

RRID:AB_2571622

This polyclonal targets mouse VGAT, 31-112 aa(BC052020)

View all literature mentions

Anti-Microtubule-Associated Protein 2 (MAP2) (antibody)

RRID:AB_91939

This polyclonal targets Microtubule-Associated Protein 2 (MAP2)

View all literature mentions

gamma Enolase (NSE-P1) (antibody)

RRID:AB_627513

This monoclonal targets gamma Enolase (NSE-P1)

View all literature mentions

Anti-GAD67 (antibody)

RRID:AB_2278725

This monoclonal targets GAD67

View all literature mentions

Anti-Glutamic Acid Decarboxylase 65/67 antibody produced in rabbit (antibody)

RRID:AB_477019

This polyclonal targets Glutamic Acid Decarboxylase 65/67

View all literature mentions