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Adeno-associated viral overexpression of neuroligin 2 in the mouse hippocampus enhances GABAergic synapses and impairs hippocampal-dependent behaviors.

https://doi.org/10.1016/j.bbr.2018.12.052

Van Zandt, M ; Weiss, E ; Almyasheva, A ; Lipior, S ; Maisel, S ; Naegele, J. ( January 2019 , Behavioural brain research)
null (Ed.)
The cell adhesion molecule neuroligin2 (NLGN2) regulates GABAergic synapse development, but its role inneural circuit function in the adult hippocampus is unclear. We investigated GABAergic synapses and hippo-campus-dependent behaviors following viral-vector-mediated overexpression of NLGN2. Transducing hippo-campal neurons with AAV-NLGN2 increased neuronal expression of NLGN2 and membrane localization ofGABAergic postsynaptic proteins gephyrin and GABAARγ2, and presynaptic vesicular GABA transporter protein(VGAT) suggesting trans-synaptic enhancement of GABAergic synapses. In contrast, glutamatergic postsynapticdensity protein-95 (PSD-95) and presynaptic vesicular glutamate transporter (VGLUT) protein were unaltered.Moreover, AAV-NLGN2 significantly increased parvalbumin immunoreactive (PV+) synaptic boutons co-loca-lized with postsynaptic gephyrin+puncta. Furthermore, these changes were demonstrated to lead to cognitiveimpairments as shown in a battery of hippocampal-dependent mnemonic tasks and social behaviors.
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