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

Ayelen Ivana Groisman

  • Caba,
  • Argentina
  • Ayelen I. Groisman ¹
  • , Andrea A. Aguilar ¹
  • , Alejandro F. Schinder ¹
  • , Damiana P. Giacomini ¹
  • 1 Laboratorio de Plasticidad Neuronal, Fundación Instituto Leloir Av. Patricias Argentinas 435, Buenos Aires, Argentina

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.

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