Improved learning and memory of contextual fear conditioning and hippocampal CA1 long‐term potentiation in histidine decarboxylase knock‐out mice

Abstract

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.

Ameliorating effect of histamine on impairment of cued fear extinction induced by morphine withdrawal in histidine decarboxylase gene knockout mice

“…Notably, the cued fear response is enhanced in both histamine H1 and H2 receptor knockout mice [27] . Moreover, HDC-KO mice have improved contextual and cued fear responses, which are reversed by intracerebroventricular injection of histamine immediately after training [21] . Interestingly, the inhibitory effect of morphine withdrawal on cued fear extinction was enhanced in HDC-KO mice, but histamine reversed the effect.…”

“…Both HDC-KO and WT mice had a pure C57BL/6 genetic background. To confirm the genotypes of the mice with respect to the HDC gene, tail biopsies were taken randomly from mice used in the experiment and analyzed by PCR, according to the procedure described in previous work [21,22] . The animals were housed individually in a temperature and humidity-controlled environment with ad libitum access to food and water.…”

Fear Memory

“…Since then, the effects on memory of histamine, histamine releasers, enhancers, and antagonists given into various structures of the brain were studied in different forms of memory. Most reported that histamine facilitates consolidation, but a few reported depressions of memory consolidation depending on the task and the brain site (24,42,64,66,85,101,110,119,175,181,205,351,480,601,611), so the overall picture is far from clear. At some receptors and in some brain areas, histamine enhances memory consolidation of certain tasks, and at other receptors and in other areas or tasks it may have different effects.…”

Endogenous Histamine Facilitates Long-Term Potentiation in the Hippocampus during Walking

“…Histamine has been shown to enhance hippocampal NMDA receptor currents (Bekkers, 1993;Vorobjev et al, 1993;Brown et al, 1995). LTP of the Schaffer collateral (presumed apical dendritic) synapses in CA1 in vitro was reduced in H 1 and H 2 receptor gene knock-out mice (Dai et al, 2007), but potentiation of population spikes was enhanced in mice lacking histidine decarboxylase, the enzyme responsible for the synthesis of histamine (Liu et al, 2007).…”