Astrocytic signaling supports hippocampal-prefrontal theta synchronization and cognitive function

Astrocytic signaling supports hippocampal-prefrontal theta synchronization and cognitive function Astrocytes interact with neurons at the cellular level through modulation of synaptic formation, maturation, and function, but the impact of such interaction into behavior remains unclear. Here, we studied the dominant negative SNARE (dnSNARE) mouse model to dissect the role of astrocyte-derived signaling in corticolimbic circuits, with implications for cognitive processing. We found that the blockade of gliotransmitter release in astrocytes triggers a critical desynchronization of neural theta oscillations between dorsal hippocampus and prefrontal cortex. Moreover, we found a strong cognitive impairment in tasks depending on this network. Importantly, the supplementation with D-serine completely restores hippocampal-prefrontal theta synchronization and rescues the spatial memory and long-term memory of dnSNARE mice. We provide here novel evidence of long distance network modulation by astrocytes, with direct implications to cognitive function. Foundation for Science and Technology (FCT) project (PTDC/SAU-NSC/118194/ 2010) to V.M.S., S.G.G., G.T., M.M., J.S.R., J.S.C., J.F.O. and fellowships (SFRH/BD/ 89714/2012 to V.M.S., SFRH/BPD/97281/ 2013 to J.F.O., SFRH/BD/101298/2014 to S.G.G., IF/00328/2015 to JFO, IF/01079/ 2014 to LP); Marie Curie Fellowship FP7- PEOPLE-2010-IEF 273936 and BIAL Foundation Grants 207/14 to J.F.O. and 427/14 to LP; Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01- 0145-FEDER-000013); FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and National funds, through the FCT (POCI-01- 0145-FEDER-007038)