Binding experience-relevant neuronal assemblies through disinhibition

Trabajo presentado al 12th Federation of European Neuroscience Societies (FENS): Virtual Forum of NeuroScience, celebrado del 11 al 15 de julio de 2020.Granule cells in the dentate gyrus (DGgc), a brain region important for spatial learning, are part of the engrams formed when an animal explores a new context. Previous work showed that modulation of DGgc activity by perisomatic inhibition bidirectionally regulates memory encoding. Whether this result is due to a differential recruitment of experience-relevant neuronal assemblies or the functional connectivity between them, is not yet known. We combined pharmacogenetic tools (DREADDs) to increase or decrease the activity of parvalbumin (PV)-interneurons in DG while mice encoded spatial information in the Novel Object Location task (NOL). Sixty min after memory encoding in the NOL task animals were sacrificed and their brains processed and quantified for c-Fos staining. Exploration in the NOL task induced a robust increase in the number of c-Fos+ cells across hippocampal subfields. However, the number of c-Fos+ cells, both in the hippocampus and extra-hippocampal structures like the medial prefrontal cortex (mPFC) and the nucleus accumbens, was constant regardless of the inhibitory tone in the DG. Only a moderate increase in c-Fos intensity per cell in DGgc was found in the PV-cell inhibition group. In contrast, we found a significant increase in the correlation between the number of c-Fos+ cells in all quantified neuronal assemblies during PV-inhibition, and a decrease during activation. Together, these data reveal a critical regulatory role of perisomatic inhibition in the dentate gyrus in binding experience-relevant neuronal assemblies in memory.This work was supported by the Spanish Ministerio de Economía y Competitividad (MINECO) and FEDER funds under the grant PGC2018-101055-B-100).Peer reviewe