Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom.
J Neurosci. 2010 Jan 6;30(1):110-5. doi: 10.1523/JNEUROSCI.4125-09.2010.
GABAergic synaptic inputs targeting cortical principal cells undergo marked changes in their functional properties from depolarizing at early postnatal life to hyperpolarizing at mature stages. In contrast, the nature of GABA(A) receptor-mediated signaling in interneurons during maturation of neuronal networks is controversial. By using gramicidin perforated-patch and whole-cell recordings from LIM homeobox 6 (Lhx6)-positive dentate gyrus perisomatic-targeting parvalbumin-expressing interneurons (PV-INs), we show that signaling at first formed GABAergic synapses at postnatal day 3 (P3) is excitatory and switches to shunting during the course of the first to second postnatal week. GABAergic synaptic inputs at P3-P6 reliably evoke action potentials in 65% of Lhx6-EGFP-expressing perisomatic-targeting cells and boost spike induction upon conjoint activation of glutamatergic fibers. Thus, GABAergic inputs change their functional role during maturation. They facilitate the recruitment of perisomatic-targeting INs in early postnatal circuits when network connectivity and synaptic glutamate receptor-mediated excitation are low and control spike timing at later stages when connectivity and glutamate-mediated drive are high.
靶向皮质主细胞的 GABA 能突触输入在其功能特性上发生了显著变化,从出生后早期的去极化转变为成熟阶段的超极化。相比之下,神经元网络成熟过程中中间神经元 GABA(A) 受体介导的信号转导性质仍存在争议。通过使用革兰氏阳性菌素穿孔贴片和 LIM 同源盒 6(Lhx6)阳性齿状回周体靶向表达小清蛋白的中间神经元(PV-INs)的全细胞记录,我们发现,在出生后第 3 天(P3)首次形成的 GABA 能突触的信号传导是兴奋性的,并在第一到第二周的过程中转变为分流。在 P3-P6 期间,GABA 能突触输入可靠地在 65%的 Lhx6-EGFP 表达的周体靶向细胞中引发动作电位,并在谷氨酸能纤维共同激活时增强尖峰诱导。因此,GABA 能输入在成熟过程中改变了它们的功能作用。当网络连接和突触谷氨酸受体介导的兴奋较低时,它们促进了周体靶向中间神经元在早期出生后回路中的募集,而当连接和谷氨酸介导的驱动较高时,它们控制着尖峰的定时。