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

Abstract

Action potential (AP) shape is a critical electrophysiological parameter, in particular because it strongly modulates neurotransmitter release. AP shape is also used to distinguish neuronal populations, as it greatly varies between neuronal types. For instance, AP duration ranges from hundreds of microseconds in cerebellar granule cells to 2-3 milliseconds in substantia nigra pars compacta (SNc) dopaminergic (DA) neurons. While most of this variation seems to arise from differences in the subtypes of voltage-and calcium-gated ion channels expressed, a few studies suggested that dendritic morphology may also affect AP shape. However, AP duration also displays significant variability in a same neuronal type, while 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 SNc DA neurons. In this neuronal type where the axon arises from an axon-bearing dendrite (ABD), the duration of the somatic AP could be predicted from a linear combination of the complexities of the ABD and the non-ABDs. Dendrotomy simulation and experiments 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 somato-dendritic compartment. In addition, dendritic morphology also modulated AP back-propagation efficiency in response to barrages of EPSCs in the ABD. In line with previous findings, these results demonstrate that dendritic morphology plays a major role in defining the electrophysiological properties of SNc DA neurons and their cell-to-cell variations.

Amygdalo-nigral inputs target dopaminergic and GABAergic neurons in the primate: a view from dendrites and soma

“…Examining and quantifying terminals in the PBP and A8 under higher magnification, we found that the propensity of CeN labeled terminals to contact either DA or GABAergic cell type was approximately equal, regardless of positions at proximal versus distal regions of the dendritic arbor. A reason for examining afferent synapses onto cell soma and their proximal dendrites is that these contacts physiologically privleged, having an outside effect on inducing action potentials (Hausser et al, 1995; Seutin and Engel, 2010; Moubarak et al, 2022). On DA neurons, the axon hillock is often found on large diameter proximal dendrites close to the soma(Juraska et al, 1977; Grace and Bunney, 1983).…”

“…On DA neurons, the axon hillock is often found on large diameter proximal dendrites close to the soma(Juraska et al, 1977; Grace and Bunney, 1983). Here, somatodendritic morphology is plays a causative role in action potential initiation and duration(Hausser et al, 1995; Meza et al, 2018; Moubarak et al, 2022). In GABAergic neurons, action potentials almost always begin at the soma where the axon originates (Hausser et al, 1995).…”

“…An important issue in studying afferents onto DA and GABAergic neurons is that terminals have differential effects depending on relative contact in dendritic compartments and proximity to the axon. In both DA and GABAergic neurons, afferent terminal contacts near the soma and large proximal dendrites are relatively physiologically potent (Hausser et al, 1995; Seutin and Engel, 2010; Moubarak et al, 2022). This is due their proximity to the axon initial segment, which integrates incoming electrical activity and ultimately produces action potentials (Grace and Bunney, 1983; Tepper et al, 1987; Meza et al, 2018).…”