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In vivo administration of epidermal growth factor and its homologue attenuates developmental maturation of functional excitatory synapses in cortical GABAergic neurons
Author(s) -
Nagano Tadasato,
Namba Hisaaki,
Abe Yuichi,
Aoki Hiroyuki,
Takei Nobuyuki,
Nawa Hiroyuki
Publication year - 2007
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2007.05297.x
Subject(s) - ampa receptor , gabaergic , neocortex , epidermal growth factor , glutamate receptor , biology , excitatory postsynaptic potential , neuroscience , transforming growth factor , endocrinology , medicine , receptor , inhibitory postsynaptic potential , biochemistry
The ErbB1 ligand family includes epidermal growth factor (EGF), transforming growth factor‐α (TGFα), heparin‐binding EGF‐like growth factor, amphiregulin and betacellulin. Previously, we demonstrated that TGFα decreases α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)‐type glutamate receptors in cultured neocortical γ‐aminobutyric acid (GABA) neurons. In the present study, we examined in vivo effects of EGF and TGFα in the mouse neocortex using electrophysiological and biochemical techniques. In mouse neonates, subcutaneously administered EGF penetrated the blood–brain barrier and activated ErbB1 in the neocortex. Daily administration of EGF or TGFα attenuates developmental increases in expression of the AMPA receptor subunits (GluR1 and GluR2/3) in the neocortex of postnatal mice. Immunohistochemistry revealed that the reduction in AMPA receptor expression was significant in the GABAergic neurons, especially those positive for parvalbumin. Using cortical slices prepared from EGF‐treated mice, we recorded miniature excitatory postsynaptic currents (mEPSCs) in both GABAergic and pyramidal neurons. Subchronic treatment with EGF decreased the amplitude and frequency of mEPSCs in GABAergic neurons, but its effects were negligible on pyramidal neurons. We conclude that EGF or other ErbB1 ligand(s) attenuates a developmental increase in AMPA receptor expression and function in cortical GABAergic neurons.