Robustness to Axon Initial Segment Variation Is Explained by Somatodendritic Excitability in Rat Substantia Nigra Dopaminergic Neurons

Estelle Moubarak (1) , Dominique Engel (2) , Martial A Dufour (1) , Mónica Tapia (1) , Fabien Tell (1) , Jean-Marc Goaillard (1)

1 UNIS - Inserm U1072 - Unité de Neurobiologie des canaux Ioniques et de la Synapse
2 GIGA-Research - Groupe Interdisciplinaire de Génoprotéomique Appliquée

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.

Keywords: action potential; axon initial segment; modeling; robustness; sodium channels; variability

Domains: Neurobiology

Estelle Moubarak, Dominique Engel, Martial A Dufour, Mónica Tapia, Fabien Tell, et al.. Robustness to Axon Initial Segment Variation Is Explained by Somatodendritic Excitability in Rat Substantia Nigra Dopaminergic Neurons. Journal of Neuroscience, 2019, ⟨10.1523/JNEUROSCI.2781-18.2019⟩. ⟨hal-02457775⟩