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Title: Adeno-associated viral overexpression of neuroligin 2 in the mouse hippocampus enhances GABAergic synapses and impairs hippocampal-dependent behaviors.
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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Behavioural brain research
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National Science Foundation
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