CUED Publications database

M-type channels selectively control bursting in rat dopaminergic neurons

Drion, G and Bonjean, M and Waroux, O and Scuvée-Moreau, J and Liégeois, J-F and Sejnowski, TJ and Sepulchre, R and Seutin, V (2010) M-type channels selectively control bursting in rat dopaminergic neurons. European Journal of Neuroscience, 31. pp. 827-835. ISSN 0953-816X

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Abstract

Midbrain dopaminergic neurons in the substantia nigra, pars compacta and ventral tegmental area are critically important in many physiological functions. These neurons exhibit firing patterns that include tonic slow pacemaking, irregular firing and bursting, and the amount of dopamine that is present in the synaptic cleft is much increased during bursting. The mechanisms responsible for the switch between these spiking patterns remain unclear. Using both in-vivo recordings combined with microiontophoretic or intraperitoneal drug applications and in-vitro experiments, we have found that M-type channels, which are present in midbrain dopaminergic cells, modulate the firing during bursting without affecting the background low-frequency pacemaker firing. Thus, a selective blocker of these channels, 10,10-bis(4-pyridinylmethyl)-9(10H)- anthracenone dihydrochloride, specifically potentiated burst firing. Computer modeling of the dopamine neuron confirmed the possibility of a differential influence of M-type channels on excitability during various firing patterns. Therefore, these channels may provide a novel target for the treatment of dopamine-related diseases, including Parkinson's disease and drug addiction. Moreover, our results demonstrate that the influence of M-type channels on the excitability of these slow pacemaker neurons is conditional upon their firing pattern. © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Item Type: Article
Uncontrolled Keywords: Firing patterns M-current Modeling Slow pacemakers Small conductance Ca2+-activated K+-channels Substantia nigra
Subjects: UNSPECIFIED
Divisions: Div F > Control
Depositing User: Cron Job
Date Deposited: 07 Mar 2014 11:28
Last Modified: 08 Dec 2014 02:18
DOI: 10.1111/j.1460-9568.2010.07107.x