Impairment of spatial learning and hippocampal synaptic potentiation in c-kit mutant rats.
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.
Katafuchi
T
T
Department of Integrative Physiology, Graduate School of Medical Sciences Kyushu University, Fukuoka 812-8582 Japan. kataf@physiol.med.kyushu-u.ac.jp
Li
A J
AJ
Hirota
S
S
Kitamura
Y
Y
Hori
T
T
D000818:Animals; D004558:Electric Stimulation; D006624:Hippocampus / Q000502:physiology*; D006720:Homozygote; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D051381:Rats; D011922:Rats, Mutant Strains; D017384:Sequence Deletion; D009435:Synaptic Transmission / Q000502:physiology*
D019009:Proto-Oncogene Proteins c-kit