Abstract |
Recent studies indicate that the histaminergic system, which is critical for wakefulness, also influences learning and memory by interacting with cholinergic systems in the brain. Histamine-containing neurones of the tuberomammillary nucleus densely innervate the cholinergic and GABAergic nucleus of the medial septum/diagonal band of Broca (MSDB) which projects to the hippocampus and sustains hippocampal theta rhythm and associated learning and memory functions. Here we demonstrate that histamine, acting via H(1) and/or H(2) receptor subtypes, utilizes direct and indirect mechanisms to excite septohippocampal GABA-type neurones in a reversible, reproducible and concentration-dependent manner. The indirect mechanism involves local ACh release, is potentiated by acetylcholinesterase inhibitors and blocked by atropine methylbromide and 4-DAMP mustard, an M(3) muscarinic receptor selective antagonist. This indirect effect, presumably, results from a direct histamine-induced activation of septohippocampal cholinergic neurones and a subsequent indirect activation of the septohippocampal GABAergic neurones. In double-immunolabelling studies, histamine fibres were found in the vicinity of both septohippocampal cholinergic and GABAergic cell types. These findings have significance for Alzheimer's disease and other neurodegenerative disorders involving a loss of septohippocampal cholinergic neurones as such a loss would also obtund histamine effects on septohippocampal cholinergic and GABAergic functions and further compromise hippocampal arousal and associated cognitive functions.
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Authors | Changqing Xu, Kimmo A Michelsen, Min Wu, Elena Morozova, Pertti Panula, Meenakshi Alreja |
Journal | The Journal of physiology
(J Physiol)
Vol. 561
Issue Pt 3
Pg. 657-70
(Dec 15 2004)
ISSN: 0022-3751 [Print] England |
PMID | 15486020
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Histamine Antagonists
- Muscarinic Antagonists
- Receptors, Histamine H1
- Receptors, Histamine H2
- gamma-Aminobutyric Acid
- Histamine
- Acetylcholine
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Topics |
- Acetylcholine
(physiology)
- Animals
- Hippocampus
(drug effects, physiology)
- Histamine
(pharmacology, physiology)
- Histamine Antagonists
(pharmacology)
- Muscarinic Antagonists
(pharmacology)
- Neurons
(drug effects, physiology)
- Rats
- Rats, Sprague-Dawley
- Receptors, Histamine H1
(drug effects, physiology)
- Receptors, Histamine H2
(drug effects, physiology)
- Septal Nuclei
(drug effects, physiology)
- gamma-Aminobutyric Acid
(physiology)
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