title: Histamine receptor expression, hippocampal plasticity and ammonia in histidine decarboxylase knockout mice.
abstract: 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.
authors.affiliation: Department of Neurophysiology, Heinrich-Heine-Universität, 40001, Düsseldorf, Germany.
authors.forename: Aisa
authors.initials: A
authors.lastname: Chepkova
authors.forename: Evgenij
authors.initials: E
authors.lastname: Yanovsky
authors.forename: Regis
authors.initials: R
authors.lastname: Parmentier
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohtsu
authors.forename: Helmut L
authors.initials: HL
authors.lastname: Haas
authors.forename: Jian-Sheng
authors.initials: JS
authors.lastname: Lin
authors.forename: Olga A
authors.initials: OA
authors.lastname: Sergeeva
mesh_terms: D000641:Ammonia / Q000097:blood / Q000378:metabolism*; D000818:Animals; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006632:Histamine / Q000494:pharmacology; D017442:Histamine Agonists / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000235:genetics*; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics*; D011968:Receptors, Histamine / Q000235:genetics* / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics
chemical_list: D017442:Histamine Agonists; D008761:Methylhistamines; D011968:Receptors, Histamine; D018100:Receptors, Histamine H3; C069357:alpha-methylhistamine; D000641:Ammonia; D006632:Histamine; D006640:Histidine Decarboxylase