Postnatal Development Of Dendritic Morphology And Action Potential Shape In Rat Substantia Nigra Dopaminergic Neurons

Abstract

Substantia nigra pars compacta (SNc) dopaminergic (DA) neurons are characterized by specific morphological and electrophysiological properties. First, in [~]90% of the cases, their axon arises from an axon-bearing dendrite (ABD) at highly variable distances from the soma. Second, they display a highly regular pattern of spontaneous activity (aka pacemaking) and a broad action potential (AP) that faithfully back-propagate through the entire dendritic arbor. In previous studies (Moubarak et al., 2019; Moubarak et al., 2022), we demonstrated that the presence of a high density of sodium current in the ABD and the complexity of this dendrite played a critical role in the robustness of pacemaking and setting the half-width of the AP. In the current study, we investigated the postnatal development of both morphology and AP shape in SNc DA neurons in order to determine when and how the mature electrophysiological phenotype of these neurons was achieved. To do so, we performed electrophysiological recordings of SNc DA neurons at 4 postnatal ages (P3, P7, P14, P21) and fully reconstructed their dendritic and proximal axon morphology. Our results show that several morphological parameters, including the length of the ABD, display abrupt changes between P7 and P14, such that a mature morphology is reached by P14. We then showed that AP shape followed a similar timecourse. Using realistic multicompartment Hodgkin-Huxley modeling, we then demonstrated that the rapid morpho-electrical maturation of SNc DA neurons likely arises from synergistic increases in dendritic length and in somatodendritic sodium channel density. Significance statementSubstantia nigra pars compacta (SNc) dopaminergic (DA) neurons display several morphological and electrophysiological peculiarities. For instance, their axon arises in most cases from an axon-bearing dendrite (ABD) and their action potential (AP) is broad and faithfully back-propagates through the entire dendritic tree. In the present study, we performed electrophysiological recordings, neuronal reconstruction and computational modeling to determine the postnatal development of dendritic morphology and AP shape in SNc DA neurons. We found that ABD length rapidly increases after post-natal day 7 (P7) to reach maturity by P14 and that AP shape follows a similar timecourse. Computational modeling then suggested that the achievement of a mature AP comes from synergistic increases in dendritic length and in somatodendritic sodium channel density.