Abstract
Neurotrophins and cytokines are involved in neuronal differentiation, synaptic development and plasticity. In neocortical culture, we reported epidermal growth factor (EGF) family (ErbB1 ligands; EGF, TGF-alpha, HB-EGF) down-regulates an AMPA receptor molecule, GluR1. Using neocortical cultures and EGF-administered animals, we electrophysiologically evaluated the effects of the EGF family on synaptic development and plasticity in the GABAergic neurons. In neocortical culture, subchronic treatment with TGF-alpha reduced the expression of GluR1-immunoreactivity in glutamic acid decarboxylase (GAD) 67 immunopositive GABAergic neurons. Whole-cell patch-clamp recording from morphologically identified putative GABAergic neurons revealed decreases both in AMPA currents and amplitudes of mEPSCs by TGF-alpha. Subcutaneous administration of EGF for 14 days in neonatal mice also decreased protein levels of AMPA and NMDA receptors in the frontal cortex. Immunohistochemical study revealed that the decrease in GluR1 levels was relatively specific for the parvalbumin-positive GABAergic neurons. Miniature analyses in cortical slices show that the amplitudes of mEPSCs in the GABAergic neurons decreased significantly, whereas no alteration was observed in the pyramidal neurons. Thus, activation of ErbB1 receptors during cortical development negatively regulates synaptic inputs and plasticity in the GABAergic neurons. [J Physiol Sci. 2006;56 Suppl:S171]
