Computational Estimation of the Distribution of L-type Ca²⁺Channels in Motoneurons Based on Variable Threshold of Activation of Persistent Inward Currents

Abstract

In the presence of neuromodulators such as serotonin and noradrenaline, motoneurons exhibit persistent inward currents (PICs) that serve to amplify synaptic inputs. A major component of these PICs is mediated by L-type Ca(2+) channels. Estimates based on electrophysiological studies indicate that these channels are located on the dendrites, but immunohistochemical studies of their precise distribution have yielded different results. Our goal was to determine the distribution of these channels using computational methods. A theoretical analysis of the activation of PICs by a somatic current injection in the absence or presence of synaptic activity suggests that L-type Ca(2+) channels may be segregated to discrete hot spots 25-200 microm long and centered 100-400 microm from the soma in the dendritic tree. Compartmental models based on detailed anatomical measurements of the structure of feline neck motoneurons with L-type Ca(2+) channels incorporated in these regions produced plateau potentials resulting from PIC activation. Furthermore, we replicated the experimental observation that the somatic threshold at which PICs were activated was depolarized by tonic activation of inhibitory synapses and hyperpolarized by tonic activation of excitatory synapses. Models with L-type Ca(2+) channels distributed uniformly were unable to replicate the change in somatic threshold of PIC activation. Therefore we conclude that the set of L-type Ca(2+) channels mediating plateau potentials is restricted to discrete regions in the dendritic tree. Furthermore, this distribution leads to the compartmentalization of the dendritic tree of motoneurons into subunits whose sequential activation lead to the graded amplification of synaptic inputs.

Staircase Currents in Motoneurons: Insight into the Spatial Arrangement of Calcium Channels in the Dendritic Tree

“…Using computational models, stepwise repolarizations from Ca 2ϩ plateaus in those neurons were attributed to the independent deactivation of L-type Ca 2ϩ channels at electrotonically segregated "hot spots." Several computational studies using motoneuron models have come to a similar conclusion: functional Ca V 1.3 channels in motoneurons are distributed in segregated regions of the dendritic tree (Bui et al, 2006;Elbasiouny et al, 2006;Grande et al, 2007a).…”

“…Several dendritic distributions patterns were explored for the Ca V 1.3 channels (Bui et al, 2006;Elbasiouny et al, 2006;Grande et al, 2007a). The conductance of the Ca V 1.3 channels g L,Ca was modeled as follows:…”

“…The fact that the individual stairs are recruited at different times suggests some aspect of spatial asymmetry in their distribution. Several studies have suggested that Ca V 1.3 channels are localized in clusters distributed at varying distances from the cell body (Carlin et al, 2000;Bui et al, 2006;Elbasiouny et al, 2006;Grande et al, 2007a). Therefore, we generated compartmental models consisting of a soma and seven three-compartment primary dendrites, only two of which contained clusters of Ca V 1.3 channels (Fig.…”

Simulation system of spinal cord motor nuclei and associated nerves and muscles, in a Web-based architecture

“…However, the neuronal models in the simulator could be improved in a wider sense to achieve an increased realism with the availability of a more powerful machine (e.g., a cluster) and the use of massively parallel algorithms (Hines et al 2008). For example, the models could include (1) more types of ionic channels in the soma (e.g., calcium dependent potassium channels, calcium channels), (2) multiple dendritic compartments to represent the spatial complexity of the dendritic tree, and (3) dendritic voltage-dependent ionic channels (Dai et al 2002;Taylor and Enoka 2004;Bui et al 2006;Vieira and Kohn 2007). These would increase the repertoire of emergent properties obtainable from the simulator at the neuronal and network levels.…”

Beginning at the end: Repetitive firing properties in the final common pathway

“…Modeling studies have also supported the presence of Ca V 1-type channels on the dendrites and have led to the suggestion that these channels have relatively low voltages of activation (Booth et al, 1997;Elbasiouny et al, 2005;Bui et al, 2006). It is important to appreciate, however, that given the inaccessibility of these channels to voltage clamp studies (see Carlin et al, 2000b), the biophysical properties of these channels are not known.…”