Models that contain the Cell : Dorsal Root Ganglion (DRG) cell

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    Models   Description
1.  A computational model of a small DRG neuron to explore pain (Verma et al. 2019, 2020)
This is a Hodgkin-Huxley type model for a small DRG neuron consisting of four voltage-gated ion channels: sodium channels 1.7 and 1.8, delayed rectifier potassium, and A-type transient potassium channels. This model was used to explore the dynamics of this neuron using bifurcation theory, with the motive to investigate pain since small DRG neuron is a pain-sensing neuron.
2.  A model of the T-junction of a C-fiber sensory neuron (Sundt et al. 2015)
The effect of geometry and ionic mechanisms on spike propagation through the T-junction of an unmyelinated sensory neuron.
3.  Computational model of bladder small DRG neuron soma (Mandge & Manchanda 2018)
Bladder small DRG neurons, which are putative nociceptors pivotal to urinary bladder function, express more than a dozen different ionic membrane mechanisms: ion channels, pumps and exchangers. Small-conductance Ca2+-activated K+ (SKCa) channels which were earlier thought to be gated solely by intracellular Ca2+ concentration ([Ca]i ) have recently been shown to exhibit inward rectification with respect to membrane potential. The effect of SKCa inward rectification on the excitability of these neurons is unknown. Furthermore, studies on the role of KCa channels in repetitive firing and their contributions to different types of afterhyperpolarization (AHP) in these neurons are lacking. In order to study these phenomena, we first constructed and validated a biophysically detailed single compartment model of bladder small DRG soma constrained by physiological data. The model includes twenty-two major known membrane mechanisms along with intracellular Ca2+ dynamics comprising Ca2+ diffusion, cytoplasmic buffering, and endoplasmic reticulum (ER) and mitochondrial mechanisms. Using modelling studies, we show that inward rectification of SKCa is an important parameter regulating neuronal repetitive firing and that its absence reduces action potential (AP) firing frequency. We also show that SKCa is more potent in reducing AP spiking than the large-conductance KCa channel (BKCa) in these neurons. Moreover, BKCa was found to contribute to the fast AHP (fAHP) and SKCa to the medium-duration (mAHP) and slow AHP (sAHP). We also report that the slow inactivating A-type K+ channel (slow KA) current in these neurons is composed of 2 components: an initial fast inactivating (time constant ~ 25-100 ms) and a slow inactivating (time constant ~ 200-800 ms) current. We discuss the implications of our findings, and how our detailed model can help further our understanding of the role of C-fibre afferents in the physiology of urinary bladder as well as in certain disorders.
4.  Criticality,degeneracy in injury-induced changes in primary afferent excitability (Ratte et al 2014)
"Neuropathic pain remains notoriously difficult to treat despite numerous drug targets. Here, we offer a novel explanation for this intractability. Computer simulations predicted that qualitative changes in primary afferent excitability linked to neuropathic pain arise through a switch in spike initiation dynamics when molecular pathologies reach a tipping point (criticality), and that this tipping point can be reached via several different molecular pathologies (degeneracy). ..."
5.  Dorsal root ganglion (DRG) neuronal model (Amir, Devor 2003)
The model shows that an electrically excitable soma is not necessary for spike through-conduction in the t-shaped geometry of a dorsal root ganglion neuron axon. Electrical excitability of the soma is required, however, for soma spike invasion. See papers for details and more.
6.  Dorsal root ganglion (DRG) neuronal model (Kovalsky et al. 2009)
This model, diverged from oscillatory parameters seen in live cells and failed to produce characteristic ectopic discharge patterns. Here we show that use of a more complete set of Na+ conductances--which includes several delayed components--enables simulation of the entire repertoire of oscillation-triggered electrogenic phenomena seen in live dorsal root ganglion (DRG) neurons. This includes a physiological window of induction and natural patterns of spike discharge. An INa+ component at 2-20 ms was particularly important, even though it represented only a tiny fraction of overall INa+ amplitude. With the addition of a delayed rectifier IK+ the singlet firing seen in some DRG neurons can also be simulated. The model reveals the key conductances that underlie afferent ectopia, conductances that are potentially attractive targets in the search for more effective treatments of neuropathic pain.
7.  DRG neuron models investigate how ion channel levels regulate firing properties (Zheng et al 2019)
We present computational models for an Abeta-LTMR (low-threshold mechanoreceptor) and a C-LTMR expressing four Na channels and four K channels to investigate how the expression level of Kv1 and Kv4 regulate number of spikes (repetitive firing) and onset latency to action potentials in Abeta-LTMRs and C-LTMRs, respectively.
8.  HMM of Nav1.7 WT and F1449V (Gurkiewicz et al. 2011)
Neuron mod files for the WT and F1449V Na+ currents from the paper: Kinetic Modeling of Nav1.7 Provides Insight Into Erythromelalgia-associated F1449V Mutation M. Gurkiewicz, A. Korngreen, S. Waxman, and A. Lampert. J.Neurophysiol. (2011). The parameters for the K65, K53 and K63 transitions were derived from microscopic reversibility relationships in the model.
9.  Models of Na channels from a paper on the PKC control of I Na,P (Baker 2005)
"The tetrodotoxin-resistant (TTX-r) persistent Na(+) current, attributed to Na(V)1.9, was recorded in small (< 25 mum apparent diameter) dorsal root ganglion (DRG) neurones cultured from P21 rats and from adult wild-type and Na(V)1.8 null mice. ... Numerical simulation of the up-regulation qualitatively reproduced changes in sensory neurone firing properties. ..." Note: models of NaV1.8 and NaV1.9 and also persistent and transient Na channels that collectively model Nav 1.1, 1.6, and 1.7 are present in this model.
10.  Origin of heterogeneous spiking patterns in spinal dorsal horn neurons (Balachandar & Prescott 2018)
"Neurons are often classified by spiking pattern. Yet, some neurons exhibit distinct patterns under subtly different test conditions, which suggests that they operate near an abrupt transition, or bifurcation. A set of such neurons may exhibit heterogeneous spiking patterns not because of qualitative differences in which ion channels they express, but rather because quantitative differences in expression levels cause neurons to operate on opposite sides of a bifurcation. Neurons in the spinal dorsal horn, for example, respond to somatic current injection with patterns that include tonic, single, gap, delayed and reluctant spiking. It is unclear whether these patterns reflect five cell populations (defined by distinct ion channel expression patterns), heterogeneity within a single population, or some combination thereof. We reproduced all five spiking patterns in a computational model by varying the densities of a low-threshold (KV1-type) potassium conductance and an inactivating (A-type) potassium conductance and found that single, gap, delayed and reluctant spiking arise when the joint probability distribution of those channel densities spans two intersecting bifurcations that divide the parameter space into quadrants, each associated with a different spiking pattern. ... "
11.  Peripheral nerve:Morris-Lecar implementation of (Schwarz et al 1995)
This is a Morris-Lecar version of the model in Schwarz et al 1995. The original model in the paper was implemented in the Hodgkin-Huxley style.
12.  TRPM8-dependent dynamic response in cold thermoreceptors (Olivares et al. 2015)
This model reproduces the dynamic response of cold thermoreceptors, transiently changing the firing rate upon heating or cooling. It also displays the 'static' or adapted firing patterns observed in these receptors.
13.  TTX-R Na+ current effect on cell response (Herzog et al 2001)
"Small dorsal root ganglion (DRG) neurons, which include nociceptors, express multiple voltage-gated sodium currents. In addition to a classical fast inactivating tetrodotoxin-sensitive (TTX-S) sodium current, many of these cells express a TTX-resistant (TTX-R) sodium current that activates near -70 mV and is persistent at negative potentials. To investigate the possible contributions of this TTX-R persistent (TTX-RP) current to neuronal excitability, we carried out computer simulations using the Neuron program with TTX-S and -RP currents, fit by the Hodgkin-Huxley model, that closely matched the currents recorded from small DRG neurons. ..." See paper for more and details.

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