Modeling Thalamocortical Cell: Impact of Ca2+ Channel Distribution and Cell Geometry on Firing Pattern

Abstract

The infl uence of calcium channel distribution and geometry of the thalamocortical cell upon its tonic fi ring and the low threshold spike (LTS) generation was studied in a 3-compartment model, which represents soma, proximal and distal dendrites as well as in multi-compartment model using the morphology of a real reconstructed neuron. Using an uniform distribution of Ca 2+ channels, we determined the minimal number of low threshold voltage-activated calcium channels and their permeability required for the onset of LTS in response to a hyperpolarizing current pulse. In the 3-compartment model, we found that the channel distribution infl uences the fi ring pattern only in the range of 3% below the threshold value of total T-channel density. In the multi-compartmental model, the LTS could be generated by only 64% of unequally distributed T-channels compared to the minimal number of equally distributed T-channels. For a given channel density and injected current, the tonic fi ring frequency was found to be inversely proportional to the size of the cell. However, when the Ca 2+ channel density was elevated in soma or proximal dendrites, then the amplitude of LTS response and burst spike frequencies were determined by the ratio of total to threshold number of T-channels in the cell for a specifi c geometry.

The interplay of seven subthreshold conductances controls the resting membrane potential and the oscillatory behavior of thalamocortical neurons

“…Although the subcellular compartmentalization of the conductances analyzed in this study could have an unforeseen impact on the conclusions reached in our study (for example, see Wei et al 2011;Zomorrodi et al 2008), the fact that the model cell reproduces the electrophysiological behavior of TC neurons indicates that either the high electrotonic compactness of TC cells allows for an effective space-clamp control of a large membrane area or, alternatively, the modeled parameters capture most of the inaccuracies of recording in the soma. In any case, the simplification is validated from a phenomenological perspective, whereas further investigation is required to clarify the functional effect of subcellular localization, which is largely unknown.…”

“…These cells display two modes of firing (tonic and bursting) that originate at two different "resting" potentials and also subthreshold oscillations. Three different conductances have been shown to affect the subthreshold membrane behavior of these neurons: the potassium leak current (McCormick 1992), the hyperpolarization-activated cationic current (I h ;McCormick and Pape 1990), and the low-threshold calcium current (I T ; Jahnsen and Llinas 1984). The first two currents control RMP directly, whereas I T underlies the transient depolarization (low-threshold calcium spike) over which rides a high-frequency burst of Na ϩ action potentials elicited when the membrane potential is released from hyperpolarization (rebound burst; Jahnsen and Llinas 1984).…”

Asymmetry in Signal Propagation between the Soma and Dendrites Plays a Key Role in Determining Dendritic Excitability in Motoneurons

“…Many studies using neuron models accounted for this confounding factor by characterizing the degree of signal attenuation from the soma to the dendrites, e.g. using a coupling conductance, as the key determinant for the location dependence of VGIC activation [9]–[11].…”

Analysis of morphological features of thalamocortical neurons from the ventroposterolateral nucleus of the cat

“…In order to reach the soma, distal inputs have to be either amplified by intrinsic currents or they have to be summated. In reticular thalamic neurons, the highest density of low-threshold Ca 2þ channels (T channels) was observed on distal dendrites (Kovács et al, 2010); however, physiological (Williams and Stuart, 2000), imaging (Zhou et al, 1997), and computational studies (Zomorrodi et al, 2008) have demonstrated that the highest density of T channels in TC neurons occurs at the proximal part of the dendritic tree. Therefore, it is unlikely that individual EPSPs arriving at the distal dendrites are amplified by the T current.…”

“…Such ability of the TC system to generate a variety of oscillations triggered a large number of modeling studies involving TC neurons (Bazhenov et al, 1998(Bazhenov et al, , 2002Destexhe et al, 1998;Destexhe and Sejnowski, 2001;Hill and Tononi, 2004;Rhodes and Llinás, 2005;Traub et al, 2005;Zomorrodi et al, 2008). In the majority of these models the electrophysiological properties of the neurons were simulated based on known conductances.…”