NEUROLIGIN-1 IN ASTROCYTE-SYNAPSE CROSSTALK

Neuroligin-1 (NLGN1) is a synaptic cell adhesion protein known for its role as an excitatory synapse organizer in neurons and has been linked to neurodevelopmental disorders such as autism spectrum disorder. A number of recent studies employing large scale RNA sequencing or proteomics have identified neuroligins, as well as other synaptic proteins such as neurexins, PSD95 or AMPA receptors in astrocytes. In particular, astrocytic neuroligin 2 has been shown to modulate astrocyte morphology and excitatory synapse formation during development. However, the function of NLGN1 in astrocytes remains poorly understood with conflicting findings in the literature. To address this, we set out to investigate the role of astrocytic NLGN1 in astrocytes-synapse crosstalk. Using an AP-NLGN1 KI mouse model developed in our laboratory, we show that NLGN1 is expressed in astrocytes in the hippocampus in vitro and in vivo and accounts for about a third of total NLGN1 in hippocampal organotypic slices. In addition, we find astrocytic NLGN1 clusters close to the excitatory synaptic compartment and show that they are able to interact with pre-synaptic neurexins. Finally, preliminary experiments using a conditional KO of NLGN1 in astrocytes suggest an impact of astrocytic NLGN1 loss on synaptic plasticity and astrocyte morphology in the hippocampus of adult mice. These findings reveal a role for NLGN1 beyond neurons and highlight the importance of the crosstalk between astrocytes and synapses.