Neuroligin 2 deletion alters inhibitory synapse function and anxiety-associated neuronal activation in the amygdala

Babaev, Olga; Botta, Paolo; Meyer, E.; Müller, Christian; Ehrenreich, Hannelore; Lüthi, Andreas; Krueger‐Burg, Dilja

doi:10.1016/j.neuropharm.2015.06.016

Cited by 59 publications

(104 citation statements)

References 31 publications

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“…Moreover, collagen XIX likely acts on inhibitory axons and terminals before postsynaptic inducers of presynaptic differentiation at these synapses, such as NCAM, Neuroligin 2, L1, and Slitrk3 (Graf et al, 2004;Guan and Maness, 2010;Takahashi et al, 2012;Woo et al, 2013;Liang et al, 2015;Maro et al, 2015;Tu et al, 2015). This may explain why inhibitory terminals initially form in the forebrain in the absence of some of these synaptic inducers, such as Neuroligin 2 (Gibson et al, 2009;Poulopoulos et al, 2009;Jedlicka et al, 2011;Liang et al, 2015;Babaev et al, 2016). Although our experiments suggest that matricryptins derived from collagen XIX are sufficient to trigger inhibitory nerve terminal assembly in vitro, the eventual loss of inhibitory synapses in the absence of Neuroligin 2 (Liang et al, 2015) suggests that collagen XIX is not sufficient for inhibitory synapse maintenance in vivo.…”

Section: Discussionmentioning

confidence: 75%

Collagen-derived matricryptins promote inhibitory nerve terminal formation in the developing neocortex

Su¹,

Jiang²,

Lippold³

et al. 2016

J Exp Med

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Section: Discussionmentioning

confidence: 75%

Collagen-derived matricryptins promote inhibitory nerve terminal formation in the developing neocortex

Su¹,

Jiang²,

Lippold³

et al. 2016

J Exp Med

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“…Studies in NL2 -deficient mice have reported that NL2 deletion disrupts the inhibitory synapse function in hippocampal sections without affecting their numbers and also triggers a pronounced anxiety phenotype in those mice [230]. In addition, NL2 deletion also affects inhibitory synapses in projection neurons of the basal amygdala, leading to their excessive activation under anxiogenic conditions [231]. Overexpression of NL2 caused different social and emotional behaviors in rats such as reduced aggression [232], whereas transgenic mice exhibited a stereotypical jumping behavior, anxiety, and impaired social interactions, probably as a consequence of a significant increase in the density of inhibitory synapses and the subsequent morphological change in the excitatory synapse [233].…”

Section: Postsynaptic Proteinsmentioning

confidence: 99%

Emerging Synaptic Molecules as Candidates in the Etiology of Neurological Disorders

2017

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Synapses are complex structures that allow communication between neurons in the central nervous system. Studies conducted in vertebrate and invertebrate models have contributed to the knowledge of the function of synaptic proteins. The functional synapse requires numerous protein complexes with specialized functions that are regulated in space and time to allow synaptic plasticity. However, their interplay during neuronal development, learning, and memory is poorly understood. Accumulating evidence links synapse proteins to neurodevelopmental, neuropsychiatric, and neurodegenerative diseases. In this review, we describe the way in which several proteins that participate in cell adhesion, scaffolding, exocytosis, and neurotransmitter reception from presynaptic and postsynaptic compartments, mainly from excitatory synapses, have been associated with several synaptopathies, and we relate their functions to the disease phenotype.

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“…One of these components is Neuroligin-2 (Nlgn2), a postsynaptic adhesion protein that is localized selectively to inhibitory synapses (8)(9)(10) and that has been linked to anxiety disorders and co-morbid autism and schizophrenia (11,12). Deletion of Nlgn2 in mice results in impaired inhibitory synaptic transmission in the hippocampus, amygdala and cortex (8,10,(13)(14)(15)(16) as well as a profoundly abnormal anxiety phenotype (15,17,18). These observations indicate that loss of inhibitory synaptic transmission in the Nlgn2 knockout (KO) mice results in aberrant activation of the anxiety network, providing a unique opportunity to study the abnormal processing of anxiety information across the brain.…”

Section: Introductionmentioning

confidence: 99%

Altered theta / beta frequency synchrony links abnormal anxiety-related behavior to synaptic inhibition in Neuroligin-2 knockout mice

Cruces-Solis

Babaev

Ali

et al. 2019

Preprint

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Inhibitory synaptic transmission plays a key role in the circuits underlying anxiety behaviors, but the network mechanisms by which disruptions in synaptic inhibition contribute to pathological anxiety processing remain largely unknown. Here we addressed this question in mice lacking the inhibitory synapse-specific adhesion protein Neuroligin-2 (Nlgn2), which display widespread reduction in inhibitory synaptic transmission as well as a pronounced anxiety phenotype. To investigate how the lack of synaptic inhibition alters the communication between key brain regions in anxiety processing, we recorded local field potentials (LFPs) simultaneously from a network of brain regions involved in anxiety processing, including the basolateral amygdala (BLA), centromedial amygdala, bed nucleus of the stria terminalis, prefrontal cortex and ventral hippocampus (vHPC). We found that LFP power in the vHPC was profoundly increased while vHPC-directed theta frequency synchrony was disrupted in Nlgn2 KO mice under anxiogenic conditions. Instead, deletion of Nlgn2 increased beta frequency synchrony across the anxiety network, and the theta / beta synchrony ratio strongly predicted anxiety behaviors in an open field paradigm. Local deletion of Nlgn2 in the vHPC and BLA revealed that they encode distinct aspects of the anxiety phenotype of the Nlgn2 KO mice, with vHPC linked to anxiety induced freezing and BLA linked to reduction in exploratory activity.Together, our data demonstrate that alterations in long-range functional connectivity link synaptic inhibition to abnormal anxiety behaviors, and that Nlgn2 KO mice represent an interesting model to study the role of inhibitory synaptic transmission in the circuits underlying anxiety disorders.

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Neuroligin 2 deletion alters inhibitory synapse function and anxiety-associated neuronal activation in the amygdala

Cited by 59 publications

References 31 publications

Collagen-derived matricryptins promote inhibitory nerve terminal formation in the developing neocortex

Collagen-derived matricryptins promote inhibitory nerve terminal formation in the developing neocortex

Emerging Synaptic Molecules as Candidates in the Etiology of Neurological Disorders

Altered theta / beta frequency synchrony links abnormal anxiety-related behavior to synaptic inhibition in Neuroligin-2 knockout mice

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