Regulation of sharp wave-ripples by cholecystokinin-expressing interneurons and parvalbumin-expressing basket cells in the hippocampal CA3 region.

Abstract

To explore the individual and interactive effects of the interneurons cholecystokinin-expressing interneurons (CCKs) and parvalbumin-expressing basket cells (BCs) on sharp wave-ripples (SWR) and the underlying mechanisms, we constructed a mathematical model of the hippocampal CA3 network. By modulating the activity of CCKs and BCs, it was verified that CCKs inhibit the generation of SWR, while the activity of BCs affects the occurrence of SWR. Additionally, it was postulated that CCKs exert an influence on SWR through a direct mechanism, wherein CCKs directly modulate pyramidal cells (PCs). It was also discovered that BCs control SWR mainly through mutual inhibition among BCs. Furthermore, by adjusting the strength of the interaction between BCs and CCKs at various levels, it was identified that the interaction between these two types of interneurons has a relatively symmetrical effect on the regulation of SWR, functioning through a mutual inhibition mechanism. Our findings not only offer a deeper understanding of how CCKs and BCs independently regulate the generation of SWR but also provide novel insights into how changes in the strength of their interaction affect network oscillations. The results emphasize the crucial role of inhibitory interneurons in maintaining normal hippocampal oscillations, which are essential for proper brain function, particularly in the domains of memory consolidation and cognitive processes.