Case Report: Is Catatonia a Clinical Feature of the Natural Progression of NLGN2-Related Neurodevelopmental Disorder?

Functional Neuroligin-2-MDGA1 interactions differentially regulate synaptic GABAARs and cytosolic gephyrin aggregation

“…We addressed these questions by investigating the function and layerspecific composition of GABAergic synapses in hippocampal area CA1 of Nlgn2 / MDGA1 double KO and Nlgn2 KO / MDGA2 heterozygous KO mice. Given that variants of both Nlgn2 (7,(32)(33)(34)(35)(36)(37) and the MDGAs (20,(38)(39)(40)(41) have been linked to schizophrenia, autism spectrum disorders, and other brain disorders, our findings have important implications not only for understanding the basic biology of GABAergic synapses, but also for identifying potential new targets for neuropsychiatric disorders linked to dysfunction of GABAergic inhibition.…”

“…Finally, in light of the role of both Nlgn2 and MDGA1/2 in the pathophysiology of psychiatric disorders (32)(33)(34)(35)(36)(37)(38)(39)(40)(41), we assessed how the interaction between Nlgn2 and MDGAs might influence psychiatrically relevant behaviors. Nlgn2 KO causes a profound increase in anxietyrelated avoidance behaviors in mice (8,47,49), which at least partially originates from altered connectivity in hippocampal-amygdala-prefrontal circuits (50).…”

Comparative mapping of selected structural determinants on the extracellular domains of cholinesterase-like cell-adhesion molecules

“…1), was shown to alter trafficking of the mutant protein through the intracellular secretory pathway (Comoletti et al, 2004, Chih et al, 2004, De Jaco et al, 2006. Other rare variants were also found for the other NLGNs, of which most were linked to autism and related neurodevelopmental disorders (Laumonnier et al, 2004;Yan et al, 2005;Talebizadeh et al, 2006;Lawson-Yuen et al, 2008;Daoud et al, 2009;Zhang et al, 2009;Pampanos et al, 2009;Sun et al, 2011;Xu et al, 2014;Landini et al, 2016;Nakanishi et al, 2017;Quartier et al, 2019;Shillington et al, 2020;and others).…”

Altered theta and beta oscillatory synchrony in a genetic mouse model of pathological anxiety

“…[5][6][7][8] One of these components is Neuroligin-2 (Nlgn2), a postsynaptic adhesion protein that is localized selectively to inhibitory synapses [9][10][11] and that has been linked to anxiety disorders and co-morbid autism and schizophrenia. [12][13][14] Deletion of Nlgn2 in mice results in impaired inhibitory synaptic transmission in the hippocampus, amygdala and cortex 10,11,[15][16][17][18] as well as a strongly exaggerated avoidance behavior in an anxiogenic environment. 17,19,20 These observations indicate that impaired inhibitory synaptic transmission in the Nlgn2 knockout (KO) mice results in aberrant activation of the network mediating defensive behaviors, providing a unique opportunity to study the abnormal processing of anxiety-related information across the brain.…”

“…Anxiolytic medications such as benzodiazepines target the GABAergic system, and variants in components of the molecular machinery at inhibitory synapses have been associated with anxiety disorders 5‐8 . One of these components is Neuroligin‐2 (Nlgn2), a postsynaptic adhesion protein that is localized selectively to inhibitory synapses 9‐11 and that has been linked to anxiety disorders and co‐morbid autism and schizophrenia 12‐14 . Deletion of Nlgn2 in mice results in impaired inhibitory synaptic transmission in the hippocampus, amygdala and cortex 10,11,15‐18 as well as a strongly exaggerated avoidance behavior in an anxiogenic environment 17,19,20 .…”