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Journal of Integrative Neuroscience  2018, Vol. 17 Issue (4): 323-330    DOI: 10.31083/j.jin.2018.04.0409
Research article Previous articles | Next articles
A simple dynamic model that accounts for regulation of neuronal polarity
J.E. Lugo1, S. Mejia-Romero1, R. Doti1, K. Ray2, *(), S.L. Kothari3, G. S. Withers4, J. Faubert1
1 Faubert Lab, Universit ′e de Montr′ eal, H3T1P1, Canada
2 Amity School of Applied Sciences, Amity University, Rajasthan 303001, India
3 Amity Institute of biotechnology, Amity University, Rajasthan 303001, India
4 Department of Biology, Whitman College, Walla Walla, WA 99362, USA.
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Abstract  

It has been shown that competing molecular interactions of atypical protein kinase C isoforms regulate neuronal polarity. For instance, silencing one particular isoform known as protein kinase M- ζ or overexpression of a second isoform known as protein kinase C- λ in hippocampal neurons alters neuronal polarity, resulting in neurons with extra axons. In contrast, the overexpression of protein kinase M- ζ prevents axon specification. These data suggest that antagonistic competition between PKC isoforms could contribute to the development of polarity and axon specification. Here, an excitatory and inhibitory non-linear network model is employed to describe neuronal polarity under different conditions. The model shifts the balance of excitation and inhibition to replicate a variety of scenarios during axon outgrowth, which are then compared with experimental results.

Key words:  Neurites      axon formation      neuronal polarity      excitatory-inhibitory network      winner-take-all network     
Submitted:  26 July 2017      Accepted:  07 November 2017      Published:  15 November 2018     
*Corresponding Author(s):  K. Ray     E-mail:  kanadray00@gmail.com

Cite this article: 

J.E. Lugo, S. Mejia-Romero, R. Doti, K. Ray, S.L. Kothari, G. S. Withers, J. Faubert. A simple dynamic model that accounts for regulation of neuronal polarity. Journal of Integrative Neuroscience, 2018, 17(4): 323-330.

URL: 

https://jin.imrpress.com/EN/10.31083/j.jin.2018.04.0409     OR     https://jin.imrpress.com/EN/Y2018/V17/I4/323

Fig. 1.  Time lapse recording of a neuron during the development of polarity and the associated image processing. (a) Frame of original video. (b) Initial frame. (c) Initial frame thresholding. (d) Frame showing neuron structure in false color. (e) Initial frame with growth vectors, and (f) last frame with growth vectors, both in false color. (g) Growth information frame.

Fig. 2.  Time lapse recording of a neuron during the development of polarity and its theoretical comparison. (a) Normalized neurite length for eight neurites within a recorded neuron, compared with (b) Information threshold for axon determination in eight neurites.

Fig. 3.  Information threshold for axon determination in six neurites from cells expressing GFP(Green Fluorescent Protein) alone. In this case the majority of neurons have at least one axon (identified as “neurite 1”). The first neurite has an excitatory strength value of 120, which is larger than the strength value of the remaining five neurites (ED=79.8). All neurites share the same level of inhibition. Initial conditions were T=D=0. Insert image (adapted from [5]) shows a typical neuron used in this experiment.

Fig. 4.  Information threshold for axon determination in six neurites for 3xFlag-PKM-ζ. For cells overexpressing this construct, the majority of neurons did not form a defined axon. All the excitatory strength values are 29.8 (ET=ED). All neurites share the same level of inhibition.Initial conditions were T=D=0. Insert image shows a typical neuron used in this experiment. The image was adapted from [5].

Fig. 5.  Information threshold for axon determination in six neurites for 3xFlag-aPKC-λ. In this case a quarter of neurons have more than one axon. All excitatory strength values are 79.8 (ET=ED). Two neurites have k=3 and in four k=0. Initial conditions were T=D=0. Insert image (adapted from [5]) shows a typical neuron used in this experiment.

Fig. 6.  Information threshold for axon determination in six neurites for PKM-ζ-Δ Par3. In this case the majority of neurons have at least one axon but the final length of axons seems longer that the experiment described in Fig. 3. The first neurite has an excitatory strength value of 540, which is bigger than the remaining five neurites (ED=79.8). Initial conditions were T=D=0. All neurites share the same level of inhibition. The insert image (adapted from [5]) shows a typical neuron used in this experiment.

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