Dataset Information

Emergence of Mixed Mode Oscillations in Random Networks of Diverse Excitable Neurons: The Role of Neighbors and Electrical Coupling.

ABSTRACT: In this paper, we focus on the emergence of diverse neuronal oscillations arising in a mixed population of neurons with different excitability properties. These properties produce mixed mode oscillations (MMOs) characterized by the combination of large amplitudes and alternate subthreshold or small amplitude oscillations. Considering the biophysically plausible, Izhikevich neuron model, we demonstrate that various MMOs, including MMBOs (mixed mode bursting oscillations) and synchronized tonic spiking appear in a randomly connected network of neurons, where a fraction of them is in a quiescent (silent) state and the rest in self-oscillatory (firing) states. We show that MMOs and other patterns of neural activity depend on the number of oscillatory neighbors of quiescent nodes and on electrical coupling strengths. Our results are verified by constructing a reduced-order network model and supported by systematic bifurcation diagrams as well as for a small-world network. Our results suggest that, for weak couplings, MMOs appear due to the de-synchronization of a large number of quiescent neurons in the networks. The quiescent neurons together with the firing neurons produce high frequency oscillations and bursting activity. The overarching goal is to uncover a favorable network architecture and suitable parameter spaces where Izhikevich model neurons generate diverse responses ranging from MMOs to tonic spiking.

SUBMITTER: Ghosh S

PROVIDER: S-EPMC7294985 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Emergence of Mixed Mode Oscillations in Random Networks of Diverse Excitable Neurons: The Role of Neighbors and Electrical Coupling.

Ghosh Subrata S Mondal Argha A Ji Peng P Mishra Arindam A Dana Syamal K SK Antonopoulos Chris G CG Hens Chittaranjan C

Frontiers in computational neuroscience 20200608

In this paper, we focus on the emergence of diverse neuronal oscillations arising in a mixed population of neurons with different excitability properties. These properties produce mixed mode oscillations (MMOs) characterized by the combination of large amplitudes and alternate subthreshold or small amplitude oscillations. Considering the biophysically plausible, Izhikevich neuron model, we demonstrate that various MMOs, including MMBOs (mixed mode bursting oscillations) and synchronized tonic sp ...[more]

PMID: 32581757

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Project description:In mesenchymal cell motility, several migration patterns have been observed, including directional, exploratory and stationary. Two key members of the Rho-family of GTPases, Rac and Rho, along with an adaptor protein called paxillin, have been particularly implicated in the formation of such migration patterns and in regulating adhesion dynamics. Together, they form a key regulatory network that involves the mutual inhibition exerted by Rac and Rho on each other and the promotion of Rac activation by phosphorylated paxillin. Although this interaction is sufficient in generating wave-pinning that underscores cellular polarization comprised of cellular front (high active Rac) and back (high active Rho), it remains unclear how they interact collectively to induce other modes of migration detected in Chinese hamster Ovary (CHO-K1) cells. We previously developed a six-variable (6V) reaction-diffusion model describing the interactions of these three proteins (in their active/phosphorylated and inactive/unphosphorylated forms) along with other auxiliary proteins, to decipher their role in generating wave-pinning. In this study, we explored, through computational modeling and image analysis, how differences in timescales within this molecular network can potentially produce the migration patterns in CHO-K1 cells and how switching between migration modes could occur. To do so, the 6V model was reduced to an excitable 4V spatiotemporal model possessing three different timescales. The model produced not only wave-pinning in the presence of diffusion, but also mixed-mode oscillations (MMOs) and relaxation oscillations (ROs). Implementing the model using the Cellular Potts Model (CPM) produced outcomes in which protrusions in the cell membrane changed Rac-Rho localization, resulting in membrane oscillations and fast directionality variations similar to those observed experimentally in CHO-K1 cells. The latter was assessed by comparing the migration patterns of experimental with CPM cells using four metrics: instantaneous cell speed, exponent of mean-square displacement ([Formula: see text]-value), directionality ratio and protrusion rate. Variations in migration patterns induced by mutating paxillin's serine 273 residue were also captured by the model and detected by a machine classifier, revealing that this mutation alters the dynamics of the system from MMOs to ROs or nonoscillatory behaviour through variation in the scaled concentration of an active form of an adhesion protein called p21-Activated Kinase 1 (PAK). These results thus suggest that MMOs and adhesion dynamics are the key mechanisms regulating CHO-K1 cell motility.

Dataset Information

Emergence of Mixed Mode Oscillations in Random Networks of Diverse Excitable Neurons: The Role of Neighbors and Electrical Coupling.

Publications

Emergence of Mixed Mode Oscillations in Random Networks of Diverse Excitable Neurons: The Role of Neighbors and Electrical Coupling.

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