Molecular mechanisms governing the maturation of GABAergic inputs onto newborn granule cells in the adult hippocampus

ALEJANDRO F. SCHINDER; AYELEN I. GROISMAN; DAMIANA GIACOMINI ; ANDREA A. AGUILAR

Congreso; Congreso XXXV de la Sociedad Argentina de Neurociencias (SAN) con formato virtual; 2020

In all mammals, the dentate gyrus of the hippocampus (DG) produces new neurons throughout life that are known to be involved in information processing. We elaborated a detailed spatio-temporal map for the integration of adult-born granule cells (GCs) within two main populations of GABAergic interneurons of the preexisting circuit, parvalbumin (PV-INs) and somatostatin (SST-INs). However, the molecular mechanisms that govern the integration of GCs remain unknown. To study the molecular tuning of GABAergic synapses onto GCs, a retrovirus expressing shRNA against Neuroligin-2 (NL2), a molecule involved in the development of inhibitory synapses, was injected in the DG of adult mice. Spontaneous inhibitory postsynaptic currents (sIPSC) were recorded in mature or 6 week-old GCs expressing shNL2 or GFP. Our results show elevated Rinput, reduced sIPSC frequency, and increased rise-time for perisomatic but not distal inhibitory contacts in shNL2-expressing GCs. To get deep insight into the development of inhibitory synaptic contacts onto GCs, we setup a combined expansion microscopy/immunostaining protocol and we were able to track PV-IN boutons onto developing GCs. Electrophysiological recordings are underway. Our preliminary data reveal NL2 as a critical modulator for the formation and maturation of perisomatic inhibition in developing GCs of the adult brain.