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1 School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK
2
Gedeon Richter Ltd, Gyömröi u. 24, 1475, Budapest, Hungary
3
Department of Anatomy and Histology, Faculty of Veterinary Science, Szent István University, István u.2, 1078, Budapest, Hungary
4
Department of Clinical Neurobiology, Interdisciplinary Centre for Neuroscience, University of Heidelberg, 69120 Heidelberg, Germany
Abstract
The medial septal diagonal band area (MS/DB), made up of GABAergic and cholinergic neurones, plays an essential role in the generation and modulation of the hippocampal theta rhythm. To understand the part that the cholinergic neurones might play in this activity, we sought to determine whether postsynaptic nicotinic receptor responses can be detected in slices of the rodent MS/DB by puffing on acetylcholine (ACh). Neurones were characterized electrophysiologically into GABAergic and cholinergic neurones according to previous criteria. Responses of the MS/SB neurones to ACh were various combinations of fast depolarizations (1.52.5 s), fast hyperpolarizations (34 s) and slow depolarizations (2030 s), the latter two being blocked by atropine. The fast depolarizations were partially or not blocked with cadmium and low calcium, tetrodotoxin, and antagonists of other ionotropic receptors, and were antagonized with 25 µM mecamylamine. Pharmacological investigation of the responses showed that the
7* nicotinic receptor type is associated with cholinergic neurones and 10% of the GABAergic neurones, and that non
7* nicotinic receptor subtypes are associated with 50% of the GABAergic neurones. Pharmacological dissection of evoked and spontaneous postsynaptic responses, however, did not provide evidence for synaptic nicotinic receptor transmission in the MS/DB. It was concluded that nicotinic receptors, although prevalent on the somatic and/or dendritic membrane compartments of neurones in the MS/DB, are on extrasynaptic sites where they presumably play a neuromodulatory role. The presence of
7* nicotinic receptors on cholinergic neurones may also render these cells specifically vulnerable to degeneration in Alzheimer's disease.
(Received 17 June 2004;
accepted after revision 2 November 2004;
first published online 4 November 2004)
Corresponding author Z. Henderson: School of Biomedical Sciences, Worsley Building, University of Leeds, Leeds LS2 9JT, UK. Email: z.henderson{at}leeds.ac.uk
This work is dedicated to the memory of Professor E. H. Buhl.
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