Repository logo
 

How modeling can reconcile apparently discrepant experimental results: the case of pacemaking in dopaminergic neurons.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Drion, Guillaume 
Massotte, Laurent 
Sepulchre, Rodolphe  ORCID logo  https://orcid.org/0000-0002-7047-3124
Seutin, Vincent 

Abstract

Midbrain dopaminergic neurons are endowed with endogenous slow pacemaking properties. In recent years, many different groups have studied the basis for this phenomenon, often with conflicting conclusions. In particular, the role of a slowly-inactivating L-type calcium channel in the depolarizing phase between spikes is controversial, and the analysis of slow oscillatory potential (SOP) recordings during the blockade of sodium channels has led to conflicting conclusions. Based on a minimal model of a dopaminergic neuron, our analysis suggests that the same experimental protocol may lead to drastically different observations in almost identical neurons. For example, complete L-type calcium channel blockade eliminates spontaneous firing or has almost no effect in two neurons differing by less than 1% in their maximal sodium conductance. The same prediction can be reproduced in a state of the art detailed model of a dopaminergic neuron. Some of these predictions are confirmed experimentally using single-cell recordings in brain slices. Our minimal model exhibits SOPs when sodium channels are blocked, these SOPs being uncorrelated with the spiking activity, as has been shown experimentally. We also show that block of a specific conductance (in this case, the SK conductance) can have a different effect on these two oscillatory behaviors (pacemaking and SOPs), despite the fact that they have the same initiating mechanism. These results highlight the fact that computational approaches, besides their well known confirmatory and predictive interests in neurophysiology, may also be useful to resolve apparent discrepancies between experimental results.

Description

Keywords

Action Potentials, Analysis of Variance, Animals, Calcium Channels, Computational Biology, Dopamine, Dopamine Agents, Male, Mesencephalon, Models, Biological, Neurons, Rats, Rats, Wistar, Sodium Channels

Journal Title

PLoS Comput Biol

Conference Name

Journal ISSN

1553-734X
1553-7358

Volume Title

7

Publisher

Public Library of Science (PLoS)