Considerable evidence exists for an extrinsic cholinergic influence in the maturation and function of the main olfactory bulb (OB). Indeed, the presence of cholinergic centrifugal fibers originating from the magnocellular basal forebrain nuclei has been well documented in the OB, and it is also well established that a number of neurodegenerative disorders related to cholinergic systems are accompanied by olfactory dysfunctions. I n this study, we addressed the muscarinic modulation of dopaminergic (DA) neurons in the OB. For this purpose, we used different patch-clamp techniques to localize and characterize the diverse roles of muscarinic agonists on DA cells in a transgenic animal model expressing a reporter protein (GFP) under the tyrosine hydroxylase promoter. When recorded in the cell attached configuration with bicuculline and kinurenate, DA neurones were spontaneously active. Bath application of carbachol (50 microM) in slices and in enzymatically dissociated cells reduced spike discharge of DA cells in cell attached mode, an effect which was fully and rapidly reversible on washout of the agonist. In whole cell configuration no effect of the agonist was observed, unless using the perforated patch technique, suggesting the involvement of a diffusible second messenger. The muscarinic nature of this effect on DA cell firing was confirmed by the selective M2 agonist oxitremorine (10 microM), which was fully blocked by atropine 100 microM. The reduction of spike discharge induced by muscarinic receptor activation results from a membrane potential hyperpolarisation, paralleled by an outward current in voltage-clamp conditions, whereas less clear is the effect on membrane resistance. This muscarinic effect on dopaminergic interneurons may be important in modulating olfactory bulb output to central structures required for driven behaviours and may be relevant to understanding mechanisms underlying the perturbations of cholinergic inputs to cortex that occur in AIzheimer’s disease.
Cholinergic modulation of excitability in the mice olfactory bulb: effect of local application of muscarinic agonist on dopaminergic neurones
PIGNATELLI, Angela
2007
Abstract
Considerable evidence exists for an extrinsic cholinergic influence in the maturation and function of the main olfactory bulb (OB). Indeed, the presence of cholinergic centrifugal fibers originating from the magnocellular basal forebrain nuclei has been well documented in the OB, and it is also well established that a number of neurodegenerative disorders related to cholinergic systems are accompanied by olfactory dysfunctions. I n this study, we addressed the muscarinic modulation of dopaminergic (DA) neurons in the OB. For this purpose, we used different patch-clamp techniques to localize and characterize the diverse roles of muscarinic agonists on DA cells in a transgenic animal model expressing a reporter protein (GFP) under the tyrosine hydroxylase promoter. When recorded in the cell attached configuration with bicuculline and kinurenate, DA neurones were spontaneously active. Bath application of carbachol (50 microM) in slices and in enzymatically dissociated cells reduced spike discharge of DA cells in cell attached mode, an effect which was fully and rapidly reversible on washout of the agonist. In whole cell configuration no effect of the agonist was observed, unless using the perforated patch technique, suggesting the involvement of a diffusible second messenger. The muscarinic nature of this effect on DA cell firing was confirmed by the selective M2 agonist oxitremorine (10 microM), which was fully blocked by atropine 100 microM. The reduction of spike discharge induced by muscarinic receptor activation results from a membrane potential hyperpolarisation, paralleled by an outward current in voltage-clamp conditions, whereas less clear is the effect on membrane resistance. This muscarinic effect on dopaminergic interneurons may be important in modulating olfactory bulb output to central structures required for driven behaviours and may be relevant to understanding mechanisms underlying the perturbations of cholinergic inputs to cortex that occur in AIzheimer’s disease.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
