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Sunday, July 19 • 9:00pm - 10:00pm
P197: Computational Modelling of the Locus Coeruleus

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Ruben Schoeters, Thomas Tarnaud, Wout Joseph, Luc Martens, Robrecht Raedt, Emmeric Tanghe

The locus coeruleus (LC) is one of the most dominant noradrenergic systems in the brain that supplies the central nervous system with norepinephrine through widespread efferent projections. Consequently, it plays an important role in attention, feeding behaviour and sleep-to-wake transition [1]. Moreover, studies have shown that the locus coeruleus is correlated to the anticonvulsive action of vagus nerve stimulation (VNS) [2]. To date, the underlying mechanisms of VNS and the LC are, however, not fully understood. Therefore, we derived a computational model, such that in silico investigations can be performed. Based on the work of Carter et al. (2012) [3], we created a single compartment model that matched our in-vivo measurements. These were extracted from rat brains at the 4Brain lab. The original model created by Carter et al. (2012) was a conductance-based model of the locus coeruleus and hypocretin neurons, used for the investigation of the sleep-to-wake transition. When the hypocretin neurons are omitted, our measured tonic firing rate of 3.35±0.49 Hz could not be reached with the original two compartment model by means of continuous current injection. The maximal achievable tonic firing rate was 0.75 Hz for a current of 0.4 A/m², while a bursting behaviour followed by depolarization block was observed for higher inputs. When combined into a single compartment model, the required frequency is reached with a 0.39 A/m² current injection. There were no notable differences in state occupancies that could explain the difference in firing rate. Therefore, we concluded that the lower firing rate observed in the two compartment model is solely due to spatial filtering. Finally, we compared the pinch response. The pinch was modelled as a rectangular current pulse. With an amplitude of 0.0314 A/m² and pulse duration of 0.9 s, an equivalent firing rate (13.64±2.75 Hz vs.13.86 Hz) and refractory period (1.186±0.234 s vs.1.09 s, the measurements and model, respectively) are observed.

_References_

1. Purves, D., Augustine, G. J., Fitzpatrick, D., Hall, W. C., Lamantia, A.-S., Mcnamara, J. O., and Willians, S. M. (2004). Neuroscience, volume 3. 2. Raedt, R., Clinckers, R., Mollet, L., Vonck, K., El Tahry, R., Wyckhuys, T., De Herdt, V., Carrette, E., Wadman, W., Michotte, Y., Smolders, I., Boon, P., and Meurs, A. (2011). Increased hippocampal noradrenaline is a biomarker for efficacy of vagus nerve stimulation in a limbic seizure model. Journal of Neurochemistry, 117(3):461–469. 3. Carter, M. E., Brill, J., Bonnavion, P., Huguenard, J. R., Huerta, R., and de Lecea, L. (2012). Mechanism for Hypocretin-mediated sleep-to-wake transitions. Proceedings of the National Academy of Sciences, 109(39):E2635–E2644.

Speakers
RS

Ruben Schoeters

INTEC WAVES, University of Ghent - IMEC



Sunday July 19, 2020 9:00pm - 10:00pm CEST
Slot 16