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Modelling Epileptic Activity in Hippocampal CA3

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Hippocampal Microcircuits

Part of the book series: Springer Series in Computational Neuroscience ((NEUROSCI))

Abstract

This chapter is about developing a computational model of the mechanism of epileptic activity generation in the hippocampal CA3 subfield, a very well-known area that initiates it presumably due to high recurrent connectivity between its constituent neurons, specifically, epileptic activity due to degeneration of OLM interneurons. The model consists of 800 pyramidal neurons, 200 basket and 200 OLM interneurons. The degeneration of OLM interneurons primarily leads to reduced dendritic inhibition on pyramidal neurons. What this leads to is a cascade of network changes including chemical changes as validated by published literature. The biophysical features of the model are explained, and how these changes lead to epileptic activity is described and modelled. Such a proposed model would help to investigate if the progression to epileptic activity generation can be contained at some stage. This could imply a therapeutic strategy for validation using further experimental studies, hence the relevance of the model.

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Change history

  • 04 April 2019

    In the original version of this chapter the corresponding author Srinivasa B. Krothapalli’s affiliation was incorrectly mentioned as Department of Electrical Engineering, National Institute of Technology Calicut, Kattangal, Kerala, India. The affiliation is now corrected as ‘Neurophysiology Unit, Department of Neurological Sciences, Christian Medical College, Vellore, India’. The same has been updated in Contributors list in the FM.

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Correspondence to Srinivasa B. Krothapalli .

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Appendix: Additional Model Information

Appendix: Additional Model Information

Table 1 Parameters for modelling background random activity
Table 2 Synaptic parameters for neuronal connectivity in the model

Information on the Various Parameters Considered for Baseline Model

The model mentioned in this chapter is primarily based on a published model of CA3 neuron and hence adapted mainly from Neymotin et al. 2011 and Neymotin et al. 2013. The various information to build the model have been considered from the experimental and computational studies by Stewart and Fox (1990), White et al. (2000), Destexhe et al. (2003), Gloveli et al. (2005), Tort et al. (2007), Hangya et al. (2009), Stacey et al. (2009), and Neymotin et al. (2011). Modifications as mentioned in Sanjay et al*. (2015) are incorporated.

Specifically, the studies by White et al. (2000) and Gloveli et al. (2005) emphasize the importance of pyramidal-OLM interneuron connectivity in generating theta oscillations and pyramidal-basket cell connectivity in generating gamma oscillations and modulating gamma component by the theta component as observed experimentally.

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Sanjay, M., Krothapalli, S.B. (2018). Modelling Epileptic Activity in Hippocampal CA3. In: Cutsuridis, V., Graham, B., Cobb, S., Vida, I. (eds) Hippocampal Microcircuits. Springer Series in Computational Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-319-99103-0_22

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