Katafuchi T, Li A J, Hirota S, Kitamura Y, Hori T
Department of Integrative Physiology, Graduate School of Medical Sciences Kyushu University, Fukuoka 812-8582 Japan.
Learn Mem. 2000 Nov-Dec;7(6):383-92. doi: 10.1101/lm.33900.
The c-kit receptor tyrosine kinase encoded by the white-spotting (W) gene is highly expressed in rat hippocampal CA1-CA4 regions. We found an impaired spatial learning and memory in homozygous c-kit (Ws/Ws) mutant rats that have a 12-base deletion in the tyrosine kinase domain of the c-kit gene and a very low kinase activity. Electrophysiological studies in hippocampal slices revealed that the long-term potentiation (LTP) induced by the tetanic stimulation (100 Hz, 1 sec) in the mossy fiber (MF)-CA3 pathway, but not in the Schaffer collaterals/commissural-CA1 pathway, was significantly reduced in c-kit mutants compared with wild-type (+/+) rats. The paired-pulse facilitation (PPF) was measured before the tetanus and after the establishment of the LTP in each slice. The initial PPF in the MF-CA3 pathway positively correlated with the amplitude of the LTP in the wild-type rats but not in the c-kit mutant rats. Furthermore, they failed to show the normal characteristics observed in the MF-CA3 pathway of +/+ rats; that is, the negative correlation between the initial PPF and the changes in PPF measured after the LTP. These findings suggest an involvement of SCF/c-kit signaling in hippocampal synaptic potentiation and spatial learning and memory.
由白斑（W）基因编码的c-kit受体酪氨酸激酶在大鼠海马CA1-CA4区域高度表达。我们发现，在c-kit基因酪氨酸激酶结构域有12个碱基缺失且激酶活性极低的纯合c-kit（Ws/Ws）突变大鼠中，空间学习和记忆受损。海马脑片的电生理研究表明，与野生型（+/+）大鼠相比，c-kit突变体中苔藓纤维（MF）-CA3通路（而非Schaffer侧支/联合-CA1通路）由强直刺激（100 Hz，1秒）诱导的长时程增强（LTP）显著降低。在每次脑片的强直刺激前和LTP建立后测量双脉冲易化（PPF）。在野生型大鼠中，MF-CA3通路的初始PPF与LTP的幅度呈正相关，但在c-kit突变大鼠中并非如此。此外，它们未能表现出在+/+大鼠的MF-CA3通路中观察到的正常特征，即在LTP后测量的初始PPF与PPF变化之间的负相关。这些发现表明SCF/c-kit信号传导参与了海马突触增强以及空间学习和记忆。
