Electrically coupled inhibitory interneurons constrain long-range connectivity of cortical networks

Spontaneous infra-slow brain activity (ISA) exhibits a high degree of temporal synchrony, or correlation, between distant brain regions. The spatial organization of ISA synchrony is not explained by anatomical connections alone, suggesting that active neural processes coordinate spontaneous activity. Inhibitory interneurons (IINs) form electrically coupled connections via the gap junction protein connexin 36 (Cx36) and networks of interconnected IINs are known to influence neural synchrony over short distances. However, the role of electrically coupled IIN networks in regulating spontaneous correlation over the entire brain is unknown. In this study, we performed OIS imaging on Cx36−/− mice to examine the role of this gap junction in ISA correlation across the entire cortex. We show that Cx36 deletion increased long-distance intra-hemispheric anti-correlation and inter-hemispheric correlation in spontaneous ISA. This suggests that electrically coupled IIN networks modulate ISA synchrony over long cortical distances. •Spontaneous neural activity correlation was selectively altered in Cx36−/− mice.•Cx36 deletion increased local but decreased long-range intra-hemispheric correlations.•Cx36 deletion increased homotopic inter-hemispheric correlations.•Sharp transition borders between brain network nodes were blunted in Cx36−/− mice.