Early Enriched Environment Promotes Neonatal GABAergic Neurotransmission and Accelerates Synapse Maturation

Abstract

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 ϩ -Cl Ϫ 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 EEreared 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.

A Single Seizure Episode Leads to Rapid Functional Activation of KCC2 in the Neonatal Rat Hippocampus

“…In view of the widely recognized but poorly understood differences in neonatal and adult epilepsies (Moshe and Galanopoulou, 2002;Ben Ari and Holmes, 2006;Rennie and Boylan, 2007), it is intriguing that recurrent seizures at postnatal day (P) 4 -6 lead to a precocious hyperpolarizing E GABA shift in CA1 pyramidal neurons of male rats 3-5 d after seizure induction, paralleled by an increase in KCC2 expression (Galanopoulou, 2008). A similar effect was recently observed after enriched environment rearing (He et al, 2010).…”

Treatment with Enriched Environment Reduces Neuronal Apoptosis in the Periinfarct Cortex after Cerebral Ischemia/Reperfusion Injury

“…While most of the studies which tried to elucidate the possible mechanisms underlying the neuroprotective effect of EE treatment have focused on neurogenesis [23], synaptogenesis [24, 25] or angiogenesis [12], the importance of neuron survival has been neglected. As apoptosis is one of the major causes that lead to cell death after I/R injury especially in the periinfarct cortex [26], suppressing apoptosis may be an effective way to improve the survival rate of neurons and eventually benefit the prognosis after stroke.…”

Actin Aggregations Mark the Sites of Neurite Initiation

“…The G-actin and F-actin fractions were then mixed with 59 SDS sample buffer and boiled, run on SDS-PAGE, and immunoblotted for actin (1:10,000, mouse; MAB1501, Millipore, Billerica, MA). Images were quantified using ImageJ as previously described [55].…”