神经细胞之间通过特异的通讯结构——“突触”——形成功能性神经环路来传递和存储信息。突触在神经细胞持续活动影响下可发生特异性的结构和功能变化，这称之为“突触可塑性”。它在神经系统发育和学习记忆中起着至关重要的作用。在神经环路组成中，释放神经递质谷氨酸和γ—氨基丁酸（GABA）的神经元分别传递兴奋性和抑制性信息。其中占总细胞少数（约10% —20%）的GABA能神经元却对神经环路的功能平衡，复杂性以及计算建构起着关键作用，其突触传递在神经信息的编码、分选和传递中发挥重要作用。 然而，对这些少数的GABA能突触的可塑性发生机理却知之甚少。
2008年10月26日《自然—神经学》（Nature Neuroscience）在线提前发表了中科院神经所博士研究生徐春和赵漫夏完成的关于GABA能突触可塑性的发生模式和机理的重要研究工作。该项工作是在蒲慕明研究员和章晓辉研究员指导下完成。在本项工作当中，作者在急性分离的大鼠海马脑片中进行了系统的电生理研究，发现发育早期GABA能突触的可塑性表现出神经元活动频率依赖的特性——高频率神经元相关活动引起突触效能的长时程增强（LTP）；而低频活动则引起长时程减弱（LTD）。并且，GABA能突触传递中的GABAB受体信号在高频活动诱导的长时程增强（LTP）中起着门控机制，能调制此突触可塑性的频率依赖性。作者通过进一步的研究表明，高频神经元活动通过增强了突触后细胞胞内CaMKII激酶活性和细胞膜上Cl—转运体活动，进而改变胞内Cl—浓度而产生LTP。GABA突触在发育早期介导兴奋性的传递，对神经网络的形成和重塑起着关键作用。因此，这项研究工作揭示了发育中GABA能突触可塑性的发生模式和细胞分子机制，阐明了神经环路建立中GABA能突触连接的自我精细修整（refinement）的工作方式。
该项研究工作受科技部973项目（2006CB806600 和2006CB943900）资助。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature Neuroscience，doi:10.1038/nn.2215，Chun Xu, Man-xia Zhao, Mu-ming Poo, Xiao-hui Zhang
GABAB receptor activation mediates frequency-dependent plasticity of developing GABAergic synapses
Chun Xu1, Man-xia Zhao1, Mu-ming Poo1,2 & Xiao-hui Zhang1
AbstractActivity-induced long-term modification of glutamatergic synapses depends on the frequency of synaptic activation. We found that long-term modification of developing rat hippocampal GABAergic synapses that was induced by repetitive coincident pre- and postsynaptic spiking was also frequency dependent. Spiking at 20–50 Hz resulted in synaptic potentiation, whereas spiking at 5 Hz led to synaptic depression. The potentiation was abolished by blocking GABAB receptors (GABABRs), whereas the depression was independent of GABABR activation and could be converted to potentiation by elevating GABABR activity. The potentiation could be attributed to a local postsynaptic increase in Na+/K+/2Cl- co-transporter activity near activated synapses. The activity of postsynaptic Ca2+/calmodulin-dependent protein kinase II was necessary for long-term potentiation of these developing GABAergic synapses and its phosphorylation at Thr286 could be enhanced by activating GABABRs with baclofen. Together with our finding that activation of GABABRs is frequency dependent, these results indicate that postsynaptic GABABR activation mediates frequency-dependent potentiation of developing GABAergic synapses.
1 Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road Shanghai 200031, China.
2 Division of Neurobiology, Department of Molecular & Cell Biology, Helen Wills Neuroscience Institute, University of California Berkeley, 221 LSA, Berkeley, California 94720, USA.
