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Histamine innervation and activation of septohippocampal GABAergic neurones: involvement of local ACh release
Author(s) -
Xu Changqing,
Michelsen Kimmo A.,
Wu Min,
Morozova Elena,
Panula Pertti,
Alreja Meenakshi
Publication year - 2004
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2004.071712
Subject(s) - histaminergic , cholinergic , neuroscience , gabaergic , diagonal band of broca , basal forebrain , hippocampus , hippocampal formation , acetylcholine , histamine , cholinergic neuron , chemistry , biology , endocrinology , inhibitory postsynaptic potential
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.