1. Robustness to Axon Initial Segment Variation Is Explained by Somatodendritic Excitability in Rat Substantia Nigra Dopaminergic Neurons
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Martial A Dufour, Estelle Moubarak, Mónica Tapia, Jean-Marc Goaillard, Dominique Engel, Fabien Tell, Unité de Neurobiologie des canaux Ioniques et de la Synapse (UNIS - Inserm U1072), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA-Research), Université de Liège, Fondation France Parkinson FRS-FNRS U.N002.13 and T.N0015.13, ANR-12-JSV4-0003,ROBUSTEX,Robustesse de l'excitabilité dans les neurones dopaminergiques(2012), and European Project: 616827,EC:FP7:ERC,ERC-2013-CoG,CANALOHMICS(2014)
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Male ,0301 basic medicine ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Models, Neurological ,Action Potentials ,Substantia nigra ,robustness ,Biology ,axon initial segment ,03 medical and health sciences ,0302 clinical medicine ,action potential ,medicine ,Animals ,Axon ,sodium channels ,Research Articles ,Pars compacta ,variability ,Dopaminergic Neurons ,General Neuroscience ,modeling ,Dendrites ,Axon initial segment ,Axons ,Rats ,Substantia Nigra ,Electrophysiology ,Somatodendritic compartment ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Female ,Soma ,Neuron ,Neuroscience ,030217 neurology & neurosurgery - Abstract
In many neuronal types, axon initial segment (AIS) geometry critically influences neuronal excitability. Interestingly, the axon of rat SNc dopaminergic (DA) neurons displays a highly variable location and most often arises from an axon-bearing dendrite (ABD). We combined current-clamp somatic and dendritic recordings, outside-out recordings of dendritic sodium and potassium currents, morphological reconstructions and multicompartment modeling on male and female rat SNc DA neurons to determine cell-to-cell variations in AIS and ABD geometry, and their influence on neuronal output (spontaneous pacemaking frequency, action potential [AP] shape). Both AIS and ABD geometries were found to be highly variable from neuron to neuron. Surprisingly, we found that AP shape and pacemaking frequency were independent of AIS geometry. Modeling realistic morphological and biophysical variations helped us clarify this result: in SNc DA neurons, the complexity of the ABD combined with its excitability predominantly define pacemaking frequency and AP shape, such that large variations in AIS geometry negligibly affect neuronal output and are tolerated. SIGNIFICANCE STATEMENT In many neuronal types, axon initial segment (AIS) geometry critically influences neuronal excitability. In the current study, we describe large cell-to-cell variations in AIS length or distance from the soma in rat substantia nigra pars compacta dopaminergic neurons. Using neuronal reconstruction and electrophysiological recordings, we show that this morphological variability does not seem to affect their electrophysiological output, as neither action potential properties nor pacemaking frequency is correlated with AIS morphology. Realistic multicompartment modeling suggests that this robustness to AIS variation is mainly explained by the complexity and excitability of the somatodendritic compartment.
- Published
- 2019
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