Models that contain the Model Concept : Pacemaking mechanism

(Usually a combination of intrinsic channels (currents) interact in pacemaker cells to cause a continual presence of action potentials.)
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    Models   Description
1.  Control of oscillations and spontaneous firing in dopamine neurons (Rumbell & Kozloski 2019)
Model of Substantia Nigra pars Compacta Dopamine Neuron. 'Toy' morphology with 4 dendrites, one of which is the axon-bearing dendrite, with an axon branching from it. The axon is a short 'axon initial segment' compartment, followed by a longer 'axon'. 727 parameter sets for ion channel conductance and kinetic parameters were found using evolutionary optimization, all of which are viable candidates representing a plausible model of a SNc DA.
2.  Determinants of the intracellular and extracellular waveforms in DA neurons (Lopez-Jury et al 2018)
To systematically address the contribution of AIS, dendritic and somatic compartments to shaping the two-component action potentials (APs), we modeled APs of male mouse and rat dopaminergic neurons. A parsimonious two-domain model, with high (AIS) and lower (dendro-somatic) Na+ conductance, reproduced the notch in the temporal derivatives, but not in the extracellular APs, regardless of morphology. The notch was only revealed when somatic active currents were reduced, constraining the model to three domains. Thus, an initial AIS spike is followed by an actively generated spike by the axon-bearing dendrite (ABD), in turn followed mostly passively by the soma. Larger AISs and thinner ABD (but not soma-to-AIS distance) accentuate the AIS component.
3.  Dopaminergic subtantia nigra neuron (Moubarak et al 2019)
Axon initial segment (AIS) geometry critically influences neuronal excitability. Interestingly, the axon of substantia nigra pars compacta (SNc) dopaminergic (DA) neurons displays a highly variable location and most often arises from an axon-bearing dendrite (ABD). We combined current-clamp somatic and dendritic recordings, outside-out recordings of dendritic sodium and potassium currents, morphological reconstructions and multi-compartment modelling to determine cell-to-cell variations in AIS and ABD geometry and their influence on neuronal output (spontaneous pacemaking frequency, AP shape). Both AIS and ABD geometries are highly variable between SNc DA neurons. Surprisingly, we found that AP shape and pacemaking frequency were independent of AIS geometry. Modelling realistic morphological and biophysical variations clarify this result: in SNc DA neurons, the complexity of the ABD combined with its excitability predominantly define pacemaking frequency and AP shape, such that large variations in AIS geometry negligibly affect neuronal output, and are tolerated.
4.  Pacemaker neurons and respiratory rhythm generation (Purvis et al 2007)
"The pre-Botzinger complex (pBC) is a vital subcircuit of the respiratory central pattern generator. Although the existence of neurons with pacemaker-like bursting properties in this network is not questioned, their role in network rhythmogenesis is unresolved. ... We modeled the parameter variability of experimental data from pBC bursting pacemaker and nonpacemaker neurons using a modified version of our previously developed pBC neuron and network models. ... " The paper contains network modeling results that are not represented in this model entry. Only the neuron models are included in this modeldb entry.
5.  Respiratory control model with brainstem CPG and sensory feedback (Diekman, Thomas, and Wilson 2017)
This is a closed-loop respiratory control model incorporating a central pattern generator (CPG), the Butera-Rinzel-Smith (BRS) model, together with lung mechanics, oxygen handling, and chemosensory components. The closed-loop system exhibits bistability of bursting and tonic spiking. Bursting corresponds to coexistence of eupnea-like breathing, with normal minute ventilation and blood oxygen level. Tonic spiking corresponds to a tachypnea-like state, with pathologically reduced minute ventilation and critically low blood oxygen. In our paper, we use the closed-loop system to demonstrate robustness to changes in metabolic demand, spontaneous autoresuscitation in response to hypoxia, and the distinct mechanisms that underlie rhythmogenesis in the intact control circuit vs. the isolated, open-loop CPG.
6.  Role of the AIS in the control of spontaneous frequency of dopaminergic neurons (Meza et al 2017)
Computational modeling showed that the size of the Axon Initial Segment (AIS), but not its position within the somatodendritic domain, is the major causal determinant of the tonic firing rate in the intact model, by virtue of the higher intrinsic frequency of the isolated AIS. Further mechanistic analysis of the relationship between neuronal morphology and firing rate showed that dopaminergic neurons function as a coupled oscillator whose frequency of discharge results from a compromise between AIS and somatodendritic oscillators.

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