Early enriched environment promotes neonatal GABAergic neurotransmission and accelerates synapse maturation.

Environmental stimulation is critical for brain development. Here, we report that natural stimulation through enriched environment (EE) rearing during the first 2 weeks of mouse postnatal development promotes GABAergic neurotransmission and accelerates maturation of GABAergic and glutamatergic synapses. Using whole-cell recordings from CA1 pyramidal neurons in acute hippocampal slices, we found that EE-reared mice exhibited higher amplitude of miniature GABAergic postsynaptic currents (mGPSCs) at 1 week of postnatal development, as well as accelerated transition of GABA action from excitation to inhibition, compared with mice reared under standard housing conditions. This enhanced GABAergic synaptic transmission persisted until the end of the second postnatal week, when GABA mostly acts as an inhibitory neurotransmitter. Consistent with these electrophysiological results, we observed elevated levels of GABA(A) receptors and the K(+)-Cl(-) cotransporter KCC2. Similarly, increased levels of excitatory synaptic components, including NMDA and AMPA receptors and the scaffolding protein PSD95, were detected in synaptosomal fractions from the forebrain/hippocampus of EE-reared mice during the first two postnatal weeks. Functional increase in glutamatergic synaptic transmission, as measured by increased amplitude of miniature and spontaneous EPSCs, was also detected during the second postnatal week. Together, these results demonstrate that early environmental stimulation through EE rearing enhances early postnatal GABAergic neurotransmission, which is known to play important trophic functions in many aspects of neural development.