Histamine Receptor Expression, Hippocampal Plasticity and Ammonia in Histidine Decarboxylase Knockout Mice
- 405 Downloads
Genetic ablation of the histamine producing enzyme histidine decarboxylase (HDC) leads to alteration in exploratory behaviour and hippocampus-dependent learning. We investigated how brain histamine deficiency in HDC knockout mice (HDC KO) affects hippocampal excitability, synaptic plasticity, and the expression of histamine receptors. No significant alterations in: basal synaptic transmission, long-term potentiation (LTP) in the Schaffer collateral synapses, histamine-induced transient changes in the CA1 pyramidal cell excitability, and the expression of H1 and H2 receptor mRNAs were found in hippocampal slices from HDC KO mice. However, when compared to WT mice, HDC KO mice demonstrated: 1. a stronger enhancement of LTP by histamine, 2. a stronger impairment of LTP by ammonia, 3. no long-lasting potentiation of population spikes by histamine, 4. a decreased expression of H3 receptor mRNA, and 5. less potentiation of population spikes by H3 receptor agonism. Parallel measurements in the hypothalamic tuberomamillary nucleus, the origin of neuronal histamine, demonstrated an increased expression of H3 receptors in HDC KO mice without any changes in the spontaneous firing of “histaminergic” neurons without histamine and their responses to the H3 receptor agonist (R)-α-methylhistamine. We conclude that the absence of neuronal histamine results in subtle changes in hippocampal synaptic transmission and plasticity associated with alteration in the expression of H3 receptors.
KeywordsLong-term potentiation Afterhyperpolarisation Ammonia Tuberomamillary nucleus (R)-α-methylhistamine
Supported by the DFG SE 1767, SFB 575/3 and 8, INSERM U628 and INSERM grant of JSL to RP.
- Dai H, Zhang Z, Zhu Y, Shen Y, Hu W, Huang Y, Luo J, Timmerman H, Leurs R, Chen Z (2006) Histamine protects against NMDA-induced necrosis in cultured cortical neurons through H receptor/cyclic AMP/protein kinase A and H receptor/GABA release pathways. J Neurochem 96:1390–1400PubMedCrossRefGoogle Scholar
- Dere E, Souza-Silva MA, Topic B, Spieler RE, Haas HL, Huston JP (2003) Histidine-decarboxylase knockout mice show deficient nonreinforced episodic object memory, improved negatively reinforced water-maze performance, and increased neo- and ventro-striatal dopamine turnover. Learn. Mem. 10:510–519PubMedCrossRefGoogle Scholar
- Lin JS, Anaclet C, Sergeeva OA, Haas HL (2011) The waking brain: an update. Cell Mol Life Sci. doi: 10.1007/s00018-011-0631-8
- Lozeva V, Tuomisto L, Tarhanen J, Butterworth RF (2003) Increased concentrations of histamine and its metabolite, tele-methylhistamine and down-regulation of histamine H3 receptor sites in autopsied brain tissue from cirrhotic patients who died in hepatic coma. J Hepatol 39:522–527PubMedCrossRefGoogle Scholar
- Ohtsu H, Tanaka S, Terui T, Hori Y, Makabe-Kobayashi Y, Pejler G, Tchougounova E, Hellman L, Gertsenstein M, Hirasawa N, Sakurai E, Buzas E, Kovacs P, Csaba G, Kittel A, Okada M, Hara M, Mar L, Numayama-Tsuruta K, Ishigaki-Suzuki S, Ohuchi K, Ichikawa A, Falus A, Watanabe T, Nagy A (2001) Mice lacking histidine decarboxylase exhibit abnormal mast cells. FEBS Lett 502:53–56PubMedCrossRefGoogle Scholar
- Parmentier R, Ohtsu H, Djebbara-Hannas Z, Valatx JL, Watanabe T, Lin JS (2002) Anatomical, physiological, and pharmacological characteristics of histidine decarboxylase knock-out mice: evidence for the role of brain histamine in behavioral and sleep-wake control. J Neurosci 22:7695–7711PubMedGoogle Scholar
- Sergeeva OA, Chepkova AN, Doreulee N, Eriksson KS, Poelchen W, Mönnighoff I, Heller-Stilb B, Warskulat U, Häussinger D, Haas HL (2003) Taurine-induced long-lasting enhancement of synaptic transmission: role of transporters. J Physio 550:911–919Google Scholar