Lu Y F, Kojima N, Tomizawa K, Moriwaki A, Matsushita M, Obata K, Matsui H
First Department of Physiology, Okayama University Medical School, Japan.
Eur J Neurosci. 1999 Jan;11(1):75-82. doi: 10.1046/j.1460-9568.1999.00407.x.
To elucidate the physiological role of Fyn, we analysed the properties of synaptic transmission and synaptic plasticity in hippocampal slices of mice overexpressing either wild-type Fyn (w-Fyn) or its constitutively active mutant (m-Fyn). These fyn-transgenes were driven by the calcium/calmodulin-dependent protein kinase II alpha promoter which turned on in the forebrain neurons including hippocampal pyramidal cells and in late neural development. In the hippocampal slices expressing m-Fyn the paired-pulse facilitation was reduced and the basal synaptic transmission was enhanced. A weak theta-burst stimulation, which was subthreshold for the induction of long-term potentiation (LTP) in control slices, elicited LTP in CA1 region of the slices expressing m-Fyn. When a relatively strong stimulation was applied, the magnitude of LTP in m-Fyn slices was similar to that in control slices. By contrast, the basal synaptic transmission and the threshold for the induction of LTP were not altered in the slices overexpressing wild-type Fyn. To examine the effect of expression of m-Fyn on GABAergic inhibitory system, we applied bicuculline, a GABAA receptor blocker, to the hippocampal slices. The ability of bicuculline to enhance excitatory postsynaptic potentials was attenuated in slices expressing m-Fyn, suggesting that the overexpression of m-Fyn reduced the GABAergic inhibition. The enhancement of synaptic transmission and the reduction of GABAergic inhibition may contribute to the enhanced seizure susceptibility in the mice expressing m-Fyn. Thus, these results suggest that regulation of Fyn tyrosine kinase activity is important for both synaptic transmission and plasticity.
为了阐明Fyn的生理作用，我们分析了过表达野生型Fyn（w-Fyn）或其组成型活性突变体（m-Fyn）的小鼠海马切片中的突触传递特性和突触可塑性。这些fyn转基因由钙/钙调蛋白依赖性蛋白激酶IIα启动子驱动，该启动子在前脑神经元（包括海马锥体细胞）和神经发育后期开启。在表达m-Fyn的海马切片中，双脉冲易化作用降低，基础突触传递增强。在对照切片中，强度较弱的θ波爆发刺激低于诱导长时程增强（LTP）的阈值，但在表达m-Fyn的切片的CA1区域却能引发LTP。当施加相对较强的刺激时，m-Fyn切片中LTP的幅度与对照切片中的相似。相比之下，过表达野生型Fyn的切片中基础突触传递和LTP诱导阈值没有改变。为了研究m-Fyn表达对GABA能抑制系统的影响，我们将GABAA受体阻断剂荷包牡丹碱应用于海马切片。在表达m-Fyn的切片中，荷包牡丹碱增强兴奋性突触后电位的能力减弱，这表明m-Fyn的过表达降低了GABA能抑制作用。突触传递的增强和GABA能抑制作用的降低可能导致表达m-Fyn的小鼠癫痫易感性增加。因此，这些结果表明Fyn酪氨酸激酶活性的调节对突触传递和可塑性都很重要。
