ArticleMolecular psychiatry2015
Conditional neuroligin-2 knockout in adult medial prefrontal cortex links chronic changes in synaptic inhibition to cognitive impairments.
Article in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 111 citations in OpenAlex.
- Early Psychosocial Neglect Adversely Impacts Developmental Trajectories of Brain Oscillations and Their Interactions.Journal of cognitive neuroscience · 2015Trial
- Baseline Dynamics and Sleep Loss-Driven Changes of Electrocorticographic Aperiodic Properties Are Altered in Mice Lacking Neuroligin-2.The European journal of neuroscience · 2026Article
- Impaired behavioral inhibition in Fmr1 KO mice is linked to disrupted visual cortex theta oscillations.Cell reports · 2026Article
- Neuroligins and Neuropathic Pain: Insights into Synaptic Plasticity and Pain Transmission.Biology · 2026Review
- Neuroligin-2-Dependent Adhesion Defines a Molecular Checkpoint for Inhibitory Synaptic Plasticity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- GARLH regulates neuroligin preference for excitatory versus inhibitory synapses.The Journal of cell biology · 2026Article
- Distinct functional domains of Dystroglycan regulate inhibitory synapse formation and maintenance in cerebellar Purkinje cells.Communications biology · 2025Article
- Article
- Essential Role of the Anterior Piriform Cortex in Mediating Social Novelty Output via a Top-Down Circuit.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Chronic stress induces depression through MDGA1-Neuroligin2 mediated suppression of inhibitory synapses in the lateral habenula.Theranostics · 2025Article
- Astrocytic Neuroligin-3 influences gene expression and social behavior, but is dispensable for synapse number.Molecular psychiatry · 2025Article
- Prefrontal cortical circuits in social behaviors: an overview.Journal of Zhejiang University. Science. B · 2024Review
- Associative memory cells of encoding fear signals and anxiety are recruited by neuroligin-3-mediated synapse formation.Communications biology · 2024Article
- Structural and functional reorganization of inhibitory synapses by activity-dependent cleavage of neuroligin-2.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The developmental timing of spinal touch processing alterations predicts behavioral changes in genetic mouse models of autism spectrum disorders.Nature neuroscience · 2024Article
- The Interplay of Astrocytes and Neurons in Autism Spectrum Disorder.Advances in neurobiology · 2024Review
- Neuroligin-2 controls the establishment of fast GABAergic transmission in adult-born granule cells.Hippocampus · 2023Article
- Neurexin-2: An inhibitory neurexin that restricts excitatory synapse formation in the hippocampus.Science advances · 2023Article
- Repeated Winning and Losing Experiences in Chronic Social Conflicts Are Linked to RNA Editing Pattern Difference.Frontiers in psychiatry · 2022Article
- Neurexins and their ligands at inhibitory synapses.Frontiers in synaptic neuroscience · 2022Review
12 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Abnormal activity in the medial prefrontal cortex (mPFC) is consistently observed in neuropsychiatric disorders, but the mechanisms involved remain unclear. Chronic aberrant excitation and/or inhibition of mPFC neurons were proposed to cause cognitive impairments. However, direct evidence for this hypothesis is lacking because it is technically challenging to control synaptic properties in a chronic and locally restricted, yet specific, manner. Here, we generated conditional knockout (cKO) mice of neuroligin-2 (Nlgn2), a postsynaptic cell-adhesion molecule of inhibitory synapses linked to neuropsychiatric disorders. cKO of Nlgn2 in adult mPFC rendered Nlgn2 protein undetectable after already 2-3 weeks, but induced major reductions in synaptic inhibition after only 6-7 weeks, and caused parallel impairments in anxiety, fear memory and social interaction behaviors. Moreover, cKO of Nlgn2 severely impaired behavioral stimulation of immediate-early gene expression in the mPFC, suggesting that chronic reduction in synaptic inhibition uncoupled the mPFC from experience-dependent inputs. Our results indicate that Nlgn2 is required for continuous maintenance of inhibitory synapses in the adult mPFC, and that chronic impairment of local inhibition disengages the mPFC from its cognitive functions by partially uncoupling the mPFC from experience-induced inputs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.