Session: 3

PS3-01 | Development of perisomatic inhibition in adult-born granule cells of the dentate gyrus: role of neuroligin-2

Andrea Aguilar

Laboratorio de Plasticidad Neuronal

Adult neurogenesis occurs throughout life in the mammalian hippocampus, and GABAergic signaling is necessary for the development and maturation of new granule cells (GCs) of the dentate gyrus (DG). We have recently shown that perisomatic inhibition by parvalbumin interneurons (PV-INs) becomes functionally mature in GCs aging >6 weeks. However, the molecular mechanisms that rule the establishment of this synapse remain unknown. We have investigated whether neuroligin-2 (NL2), a molecule involved in the development of inhibitory contacts, is involved in this process. First, we used confocal microscopy to characterize the development of synapses formed by PV-INs expressing tdTomato onto GCs expressing GFP. We quantified the area of perisomatic contacts at different time points and observed a substantial increase between 2 and 4 weeks, with no further changes at later time points. Next, we delivered a retrovirus to express a shRNA against NL2 and monitored the consequences of NL2 knockdown on the development and function of the PV-IN to GC synapse. We found no changes in the area of perisomatic inhibition in confocal images. However, electrophysiological recordings revealed immature features (slow kinetics) in both spontaneous and evoked postsynaptic currents in 6-week-old GCs with reduced NL2 levels. Our results reveal NL2 as a critical player for the functional maturation of perisomatic inhibition in developing GCs of the adult brain.