Frontiers in Systems Neuroscience (Apr 2014)
From the axons of the SNc dopamine neurons to their dendritic processes: further clues to susceptibility in Parkinson’s disease (PD)?
Abstract
Dopamine neurons of the substantia nigra pars compacta (SNc) are uniquely sensitive to degeneration in Parkinson’s disease (PD) and its models. Although a variety of molecular characteristics have been proposed to underlie this sensitivity, one possible contributory factor is their massive, unmyelinated, axonal arbor that is orders of magnitude larger than other neuronal types. In our previously published work, we examined the energetic impact imposed on SNc dopamine neurons by their extensive, unmyelinated axonal arbor and attempted to calculate the energy cost of action potential (AP) propagation throughout the axonal arbors. Among our main findings were that a) the energy demand associated with AP conduction is related in a supra-linear manner to the axonal size and complexity and, b) that synaptic stimulation is necessary to ensure reliable propagation throughout the axonal arbors of neurons with higher levels of branching. Indeed, predictions of our biophysical model of SNc dopamine neurons suggest that tonic activity for the reliable propagation of APs throughout the axonal arbour of neurons with small-to-moderate size arbours, whereas synaptic stimulation is required for for reliable propagation in neurons with larger and more complex arbors (Pissadaki and Bolam 2013). SNc dopamine neurons may thus be classified into functionally distinct groups according to the size of their axonal arborisation. Furthermore, SNc dopamine neurons are divided into ventral tier neurons, which are more susceptible in PD and extend their dendrites in both SN pars reticulata (SNr)) and SNc, and dorsal tier neurons that restrict their dendrites within SNc. As SNr dendrites receive proportionally greater inhibitory input than SNc dendrites (Henny et al 2012), we examined the relationship between the dendritic compartmentalisation, synaptic input, burst generation and the extent of axonal arborisation. Because spatiotemporal interplay of synaptic stimulation has been shown to facilitate bursting behaviour, we hypothesise that SNc neurons with dendrites in both compartments are more likely to generate bursts. Preliminary results indicate that the temporal latencies of synaptic stimulation in the two sub-cellular compartments can sculpt the output of the model neuron. These findings may represent a driving mechanism that explains how the local ongoing network activity can modulate the activity of SNc dopamine neurons and underlie changes from autonomous to burst firing.
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