A computational study of suppression of sharp wave ripple complexes by controlling calcium and gap junctions in pyramidal cells

ABSTRACT

The hippocampus plays a key role in memory formation and learning. According to the concept of active systems memory consolidation, transiently stored memory traces are transferred from the hippocampus into the neocortex for permanent storage. This phenomenon relies on hippocampal network oscillations, particularly sharp wave ripples [SPW-Rs). In this process prior saved data in the hippocampus may be reactivated. Recent investigations reveal that several neurotransmitters and neuromodulators including norepinephrine, acetylcholine, serotonin, etc., suppress SPW-Rs activity in rodents’ hippocampal slices. This suppression of SPW-Rs may depend on various presynaptic and postsynaptic parameters including decrease in calcium influx, hyperpolarization/depolarization and alteration in gap junctions’ function in pyramidal cells. In this study, we demonstrate the impact of calcium influx and gap junctions on pyramidal cells for the modulation of SPW-Rs in a computational model of CA1.

We used,SPW-Rs model with some modifications. SPW-Rs are simulated with gradual reduction of calcium and with decreasing conductance through gap junctions in PCs. Both, with calcium reduction as well as with conductance reduction through gap junctions, SPW-Rs are suppressed. Both effects add up synergistically in combination.

Graphical abstract

KEYWORDS:

• Sharp wave ripples
• hippocampus
• calcium influx
• ca1
• oscillations

Acknowledgements

The authors are grateful to Professor Dr. Uwe Heinemann (late) for his help in designing this project. This work was supported by the US-German Collaboration in Computational Neuroscience (NSF/BMBF grant 01GQ1706).

Research highlights

• Sharp-wave ripples may occur by summation of electrical coupling among CA1 cells and synaptic inputs of place cells.

• Sharp-wave ripples may be suppressed by reduction in calcium influx.

• Weak electrical coupling between place cells may weaken SPW-Rs activities.

Combined reduction of calcium influx and electrical coupling has strong suppressive effect on SPW-Rs.

Disclosure of potential conflicts of interest

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Bundesministerium für Bildung und Forschung under grant number [01GQ1706].