Axon initial segment (AIS) geometry critically influences neuronal excitability. Interestingly, the axon of substantia nigra pars compacta (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 multi-compartment modelling to determine cell-to-cell variations in AIS and ABD geometry and their influence on neuronal output (spontaneous pacemaking frequency, AP shape). Both AIS and ABD geometries are highly variable between SNc DA neurons. Surprisingly, we found that AP shape and pacemaking frequency were independent of AIS geometry. Modelling realistic morphological and biophysical variations 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.
Region(s) or Organism(s): Basal ganglia
Cell Type(s): Substantia nigra pars compacta DA cell
Simulation Environment: NEURON
Moubarak E et al. (2019). Robustness to Axon Initial Segment Variation Is Explained by Somatodendritic Excitability in Rat Substantia Nigra Dopaminergic Neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience. 39 [PubMed]