Chemical Senses Advance Access originally published online on January 21, 2008
Chemical Senses 2008 33(4):331-338; doi:10.1093/chemse/bjm091
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Cholinergic Modulation of Dopaminergic Neurons in the Mouse Olfactory Bulb
Dipartimento di Biologia ed Evoluzione, Università degli Studi di Ferrara, Via Borsari 46, 44100 Ferrara, Italy and Istituto Nazionale di Neuroscienze, Centro di Ferrara, Italy
Correspondence to be sent to: Ottorino Belluzzi, Dipartimento di Biologia ed Evoluzione, Sez. Fisiologia e Biofisica, Via Borsari 46, 44100 Ferrara, Italy. e-mail: mk5{at}unife.it
| Abstract |
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Considerable evidence exists for an extrinsic cholinergic influence in the maturation and function of the main olfactory bulb. In this study, we addressed the muscarinic modulation of dopaminergic neurons in this structure. We used different patch-clamp techniques to characterize the diverse roles of muscarinic agonists on identified dopaminergic neurons in a transgenic animal model expressing a reporter protein (green fluorescent protein) under the tyrosine hydroxylase promoter. Bath application of acetylcholine (1 mM) in slices and in enzymatically dissociated cells reduced the spontaneous firing of dopaminergic neurons recorded in cell-attached mode. In whole-cell configuration no effect of the agonist was observed, unless using the perforated patch technique, thus suggesting the involvement of a diffusible second messenger. The effect was mediated by metabotropic receptors as it was blocked by atropine and mimicked by the m2 agonist oxotremorine (10 µM). The reduction of periglomerular cell firing by muscarinic activation results from a membrane-potential hyperpolarization caused by activation of a potassium conductance. This modulation of dopaminergic interneurons may be important in the processing of sensory information and may be relevant to understand the mechanisms underlying the olfactory dysfunctions occurring in neurodegenerative diseases affecting the dopaminergic and/or cholinergic systems.
Key words: dopaminergic neurons, muscarine, olfactory bulb, patch-clamp
Accepted 16 December 2007