Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
J Neurosci. 2010 Jun 9;30(23):7910-6. doi: 10.1523/JNEUROSCI.6375-09.2010.
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.
环境刺激对大脑发育至关重要。在这里，我们报告说，在小鼠出生后发育的前 2 周内，通过丰富环境（EE）饲养进行自然刺激可促进 GABA 能神经传递，并加速 GABA 能和谷氨酸能突触的成熟。通过在急性海马脑片上从 CA1 锥体神经元进行全细胞膜片钳记录，我们发现与在标准饲养条件下饲养的小鼠相比，EE 饲养的小鼠在出生后 1 周时表现出更大幅度的 GABA 能微小突触后电流（mGPSC），并且 GABA 作用从兴奋向抑制的转变更快。这种增强的 GABA 能突触传递持续到第二个出生后周结束，此时 GABA 主要作为抑制性神经递质发挥作用。与这些电生理结果一致，我们观察到 GABA(A)受体和 K(+) -Cl(-)共转运蛋白 KCC2 的水平升高。同样，在出生后前两周，EE 饲养的小鼠的前脑/海马突触体部分中也检测到兴奋性突触成分（包括 NMDA 和 AMPA 受体以及支架蛋白 PSD95）的水平升高。通过增加微小和自发 EPSC 的幅度检测到的谷氨酸能突触传递的功能增加也在第二个出生后周中检测到。总之，这些结果表明，通过 EE 饲养进行的早期环境刺激可增强早期出生后的 GABA 能神经传递，已知其在神经发育的许多方面发挥重要的营养作用。
