Morphological Determinants of Cell-to-Cell Variations in Action Potential Dynamics in Substantia Nigra Dopaminergic Neurons

Action potential (AP) shape is a critical electrophysiological parameter, in particular because it strongly modulates neurotransmitter release. As it greatly varies between neuronal types, AP shape is also used to distinguish neuronal populations. For instance, AP dura-tion ranges from hundreds of microseconds in cerebellar granule cells to 2-3 ms in SNc dopaminergic (DA) neurons. While most of this variation across cell types seems to arise from differences in the voltage-and calcium-gated ion channels expressed, a few studies suggested that dendritic morphology also affects AP shape. AP duration also displays significant variability in a same neuronal type, although the determinants of these variations are poorly known. Using electrophysiological recordings, morphological reconstructions, and realistic Hodgkin-Huxley modeling, we investigated the relationships between dendritic morphology and AP shape in rat SNc DA neurons from both sexes. In this neuronal type where the axon arises from an axon-bearing dendrite (ABD), the duration of the so-matic AP could be predicted from a linear combination of the ABD and non-ABDs' complexities. Dendrotomy experiments and simu-lation showed that these correlations arise from the causal influence of dendritic topology on AP duration, due in particular to a high density of sodium channels in the somatodendritic compartment. Surprisingly, computational modeling suggested that this effect arises from the influence of sodium currents on the decaying phase of the AP. Consistent with previous findings, these results demon-strate that dendritic morphology plays a major role in defining the electrophysiological properties of SNc DA neurons and their cell -to-cell variations.

Automated summary

The shape of action potential (AP) is crucial in regulating neurotransmitter release and distinguishing neuronal populations. While variations in AP shape between different neuronal types are mainly attributed to differences in ion channel expression, the influence of dendritic morphology on AP shape has been suggested. This study investigates the relationship between dendritic morphology and AP shape in rat SNc DA neurons. The results demonstrate that dendritic morphology plays a significant role in defining the electrophysiological properties of SNc DA neurons.