Cellular and Molecular Neurobiology
Author: Andrea Aguilar Arredondo | email: aaguilar310780@gmail.com
Andrea Aguilar-Arredondo 1°, Damiana Giacomini 1°, Alejandro Schinder 1°
1° Leloir Institute Foundation, Neural plasticity lab
GABAergic signaling is crucial for the development and function of adult-born granule cells (aGCs). Parvalbumin interneurons (PV-INs) exert perisomatic inhibition onto aGCs that becomes functionally mature at 6 weeks of neuronal age. The molecular mechanisms orchestrating the establishment of this synapse are unknown. We investigated whether neuroligin-2 (NL2), a postsynaptic adhesion molecule involved in the development of inhibitory contacts, plays a role in perisomatic GABAergic synaptogenesis in aGCs. Using confocal microscopy, we first characterized the development of synapses formed by PV-INs expressing tdTomato onto aGCs expressing GFP, by measuring the size of perisomatic appositions at different time points. We observed a substantial increase in synaptic size from 2 to 4 weeks, with no further changes at later times. We next delivered a retrovirus expressing a shRNA against NL2 and monitored the effect of NL2 knockdown on the PV-IN to GC synapse. We found smaller synaptic contacts accompanied by an important reduction of perisomatic appositions of the vesicular GABA transporter VGAT, suggesting impaired synaptic function. Moreover, we analyzed the expression of the presynaptic active zone protein bassoon, which showed a reduction in the number of puncta within terminals of PV-INs contacting aGCs in shNL2 expressing cells. Our results reveal NL2 as a critical player in the delayed functional maturation of perisomatic inhibition in aGCs of the adult brain.