Improved learning and memory of contextual fear conditioning and hippocampal CA1 long-term potentiation in histidine decarboxylase knock-out mice.
Some studies suggest that the histaminergic system plays an important role in learning and memory. However, the results seem to be controversial in many behavioral tasks. In the present study, we used HDC knockout (HDC-KO) mice to investigate the effects of long-term histamine deficiency on learning and memory in contextual fear conditioning. We found that HDC-KO mice exhibited improved contextual fear from 1 day after training and this lasted for at least 14 days when compared with the wild-type (WT) controls. Cued fear was also improved 2 days after training in HDC-KO mice. Moreover, injection of histamine (intracerebroventricularly, 10 microg/mouse) immediately after training reversed the improvement in contextual fear conditioning when tested 1 day after training. Electrophysiological data showed that hippocampal CA1 long-term potentiation (LTP) in HDC-KO mice was much greater than that in WT mice, and paired-pulse facilitation decreased 2 h after LTP induction in HDC-KO mice. In contrast, HDC-KO mice showed smaller LTP than did WT mice 1 day after training. Hippocampal glutamate levels significantly increased in HDC-KO mice 1 and 4 days after training. The results indicated that histamine deficiency may improve consolidation of contextual fear conditioning. This improvement may be due to the increased hippocampal CA1 LTP, and presynaptic glutamate release. The relationship between behavior and synaptic plasticity provides support for the involvement of activity-dependent LTP in learning and memory.
Liu
Luying
L
Department of Pharmacology and Neurobiology, School of Medicine, Zhejiang University, Hangzhou 310058, China.
Zhang
Shihong
S
Zhu
Yongping
Y
Fu
Qiuli
Q
Zhu
Yuanyuan
Y
Gong
Yingxia
Y
Ohtsu
Hiroshi
H
Luo
Jianhong
J
Wei
Erqing
E
Chen
Zhong
Z
D000200:Action Potentials / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003214:Conditioning, Classical / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D005239:Fear; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000502:physiology*; D006632:Histamine / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000172:deficiency*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000235:genetics*; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D006632:Histamine; D006640:Histidine Decarboxylase