Evidence
Science. 2024 Mar;383(6686):eadk1291. doi: 10.1126/science.adk1291. Epub 2024 Mar 1.
ABSTRACT
SynGAP is an abundant synaptic GTPase-activating protein (GAP) critical for synaptic plasticity, learning, memory, and cognition. Mutations in SYNGAP1 in humans result in intellectual disability, autistic-like behaviors, and epilepsy. Heterozygous Syngap1-knockout mice display deficits in synaptic plasticity, learning, and memory and exhibit seizures. It is unclear whether SynGAP imparts structural properties at synapses independently of its GAP activity. Here, we report that inactivating mutations within the GAP domain do not inhibit synaptic plasticity or cause behavioral deficits. Instead, SynGAP modulates synaptic strength by physically competing with the AMPA-receptor-TARP excitatory receptor complex in the formation of molecular condensates with synaptic scaffolding proteins. These results have major implications for developing therapeutic treatments for SYNGAP1-related neurodevelopmental disorders.
PMID:38422154 | DOI:10.1126/science.adk1291
Estimated reading time: 3 minute(s)
Latest: Psychiatryai.com #RAISR4D Evidence
Cool Evidence: Engaging Young People and Students in Real-World Evidence
Real-Time Evidence Search [Psychiatry]
AI Research
SynGAP regulates synaptic plasticity and cognition independently of its catalytic activity
🌐 90 Days
AI Virtual Reality Related Evidence Matrix
- Identification of secretory autophagy as a mechanism modulating activity-induced synaptic remodeling
- Modulation of structural and functional plasticity in the hippocampus across the murine estrous cycle
- Inhibiting Hippo pathway kinases releases WWC1 to promote AMPAR-dependent synaptic plasticity and long-term memory in mice
- Low-frequency repetitive transcranial magnetic stimulation alleviates abnormal behavior in valproic acid rat model of autism through rescuing synaptic plasticity and inhibiting neuroinflammation
- Electrophysiological Phenotypes of Hippocampal Synaptic and Network Functions in Cannabinoid Receptor 2 Knockout Mice
- Presynaptic structural and functional plasticity are coupled by convergent Rap1 signaling
- Serotonin Signaling through Lipid Membranes
- SHP2 regulates GluA2 tyrosine phosphorylation required for AMPA receptor endocytosis and mGluR-LTD
- Tmod2 is a regulator of cocaine responses through control of striatal and cortical excitability, and drug-induced plasticity
- Targeted rescue of synaptic plasticity improves cognitive decline in sepsis-associated encephalopathy
- Enhanced hippocampal LTP but normal NMDA receptor and AMPA receptor function in a rat model of CDKL5 deficiency disorder
- Trans-synaptic association of vesicular zinc transporter 3 and Shank3 supports synapse-specific dendritic spine structure and function in mouse auditory cortex
- Postnatal hypofunction of N-methyl-D-aspartate receptors alters perforant path synaptic plasticity and filtering and impairs dentate gyrus-mediated spatial discrimination
- 5-HT4 receptor agonists treatment reduces tau pathology and behavioral deficit in the PS19 mouse model of tauopathy
- The interaction between KIF21A and KANK1 regulates dendritic morphology and synapse plasticity in neurons
- Resveratrol prevents cognitive deficits induced by sleep deprivation via modulating sirtuin 1 associated pathways in the hippocampus
- Distinct SAP102 and PSD-95 nano-organization defines multiple types of synaptic scaffold protein domains at single synapses
- The CHD family chromatin remodeling enzyme, Kismet, promotes both clathrin-mediated and activity-dependent bulk endocytosis
- Increased gene dosage of RFWD2 causes autistic-like behaviors and aberrant synaptic formation and function in mice
- Individual NMDA receptor GluN2 subunit signaling domains differentially regulate the postnatal maturation of hippocampal excitatory synaptic transmission and plasticity but not dendritic morphology
- Genetic background determines synaptic phenotypes in Arid1b-mutant mice
- SIK1 Downregulates Synaptic AMPA Receptors and Contributes to Cognitive Defects in Alzheimer's Disease
- Intrinsic neural excitability biases allocation and overlap of memory engrams
- Intrinsic neural excitability biases allocation and overlap of memory engrams
- Integrating analysis of mRNA expression profiles indicates Sgk1 as a key mediator in muscle-brain crosstalk during resistance exercise
- Tiam1-mediated maladaptive plasticity underlying morphine tolerance and hyperalgesia
- Tiam1-mediated maladaptive plasticity underlying morphine tolerance and hyperalgesia
- Loss of Katnal2 leads to ependymal ciliary hyperfunction and autism-related phenotypes in mice
- Sex-specific mechanisms underlie long-term potentiation at hippocampus-medium spiny neuron synapses in the medial shell of the nucleus accumbens
- Presynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment
- Termination of convulsion seizures by destabilizing and perturbing seizure memory engrams
- Structural and functional reorganization of inhibitory synapses by activity-dependent cleavage of neuroligin-2
- Structural neuroplasticity after sleep loss modifies behavior and requires neurexin and neuroligin
- Hippocampal proteome comparison of infant and adult Fmr1 deficiency mice reveals adult-related changes associated with postsynaptic density
- CaMKII activity and metabolic imbalance-related neurological diseases: Focus on vascular dysfunction, synaptic plasticity, amyloid beta accumulation, and lipid metabolism
- Artificial fluorescent sensor reveals pre-synaptic NMDA receptors switch cholecystokinin release and LTP in the hippocampus
- BDNF Signaling in Vascular Dementia and Its Effects on Cerebrovascular Dysfunction, Synaptic Plasticity, and Cholinergic System Abnormality
- Limb-Clasping Response in NMDA Receptor Palmitoylation-Deficient Mice
- Single-Molecule-Resolution Approaches in Synaptic Biology
- Light affects the prefrontal cortex via intrinsically photosensitive retinal ganglion cells
- Cell- and pathway-specific disruptions in the accumbens of Fragile X mouse
- Ab peptide enhances GluA1 internalization via lipid rafts in Alzheimer's-related hippocampal LTP dysfunction
- Directed and acyclic synaptic connectivity in the human layer 2-3 cortical microcircuit
- NMDAR (2C) deletion in astrocytes relieved LPS-induced neuroinflammation and depression
- NMDAR (2C) deletion in astrocytes relieved LPS-induced neuroinflammation and depression
- The spike-timing-dependent plasticity of VIP interneurons in motor cortex
- Synaptic alterations associated with disrupted sensory encoding in a mouse model of tauopathy
- Intrinsic and synaptic contributions to repetitive spiking in dentate granule cells
- Lifelong absence of microglia alters hippocampal glutamatergic networks but not synapse and spine density
- In vitro evaluation of PET radiotracers for imaging synaptic density, the acetylcholine transporter, AMPA-tarp-γ8 and muscarinic M4 receptors in Alzheimer's disease
- Inhibiting proBDNF to mature BDNF conversion leads to ASD-like phenotypes in vivo
- Complexin has a dual synaptic function as checkpoint protein in vesicle priming and as a promoter of vesicle fusion
- The Influence of Microglia on Neuroplasticity and Long-Term Cognitive Sequelae in Long COVID: Impacts on Brain Development and Beyond
- SEP-363856 exerts neuroprotection through the PI3K/AKT/GSK-3beta signaling pathway in a dual-hit neurodevelopmental model of schizophrenia-like mice
- SEP-363856 exerts neuroprotection through the PI3K/AKT/GSK-3β signaling pathway in a dual-hit neurodevelopmental model of schizophrenia-like mice
- SEP-363856 exerts neuroprotection through the PI3K/AKT/GSK-3β signaling pathway in a dual-hit neurodevelopmental model of schizophrenia-like mice
- Edaravone dexborneol attenuates cognitive impairment in a rat model of vascular dementia by inhibiting hippocampal oxidative stress and inflammatory responses and modulating the NMDA receptor signaling pathway
- Cerebral venous congestion alters CNS homeostatic plasticity, evoking tinnitus-like behavior
- Synapse-specific trapping of SNARE machinery proteinsin the anesthetized Drosophila brain
- Sleep disruption precedes forebrain synaptic Tau burden and contributes to cognitive decline in a sex-dependent manner in the P301S Tau transgenic mouse model
- Distinct forms of structural plasticity of adult-born interneuron spines in the mouse olfactory bulb induced by different odor learning paradigms
- A high-performance organic lithium salt-doped OFET with the optical radical effect for photoelectric pulse synaptic simulation and neuromorphic memory learning
- Kainate receptor channel opening and gating mechanism
- Adolescent Thalamocortical Inhibition Alters Prefrontal Excitation-Inhibition Balance
Evidence Blueprint
SynGAP regulates synaptic plasticity and cognition independently of its catalytic activity
☊ AI-Driven Related Evidence Nodes
(recent articles with at least 5 words in title)
More Evidence
SynGAP regulates synaptic plasticity and cognition independently of its catalytic activity
🌐 365 Days
AI Virtual Reality Related Evidence Matrix
- Amnesia after repeated head impact is caused by impaired synaptic plasticity in the memory engram
- Identification of secretory autophagy as a mechanism modulating activity-induced synaptic remodeling
- Adnp-mutant mice with cognitive inflexibility, CaMKIIα hyperactivity, and synaptic plasticity deficits
- Functional inhibition of katanin affects synaptic plasticity
- Interneuron-targeted disruption of SYNGAP1 alters sensory representations in the neocortex and impairs sensory learning
- Autism-related KLHL17 and SYNPO act in concert to control activity-dependent dendritic spine enlargement and the spine apparatus
- Tdrd3-null mice show post-transcriptional and behavioral impairments associated with neurogenesis and synaptic plasticity
- Modulation of structural and functional plasticity in the hippocampus across the murine estrous cycle
- P2Y6 receptor-dependent microglial phagocytosis of synapses during development regulates synapse density and memory
- Intrinsic plasticity of Purkinje cell serves homeostatic regulation of fear memory
- A stochastic model of hippocampal synaptic plasticity with geometrical readout of enzyme dynamics
- D-Cycloserine enhances the bidirectional range of NMDAR-dependent hippocampal synaptic plasticity
- Ablation of KIF2C in Purkinje cells impairs metabotropic glutamate receptor trafficking and motor coordination in male mice
- The DDHD2-STXBP1 interaction mediates long-term memory via generation of saturated free fatty acids
- Tumor suppressor p53 modulates activity-dependent synapse strengthening, autism-like behavior and hippocampus-dependent learning
- Inhibiting Hippo pathway kinases releases WWC1 to promote AMPAR-dependent synaptic plasticity and long-term memory in mice
- Low-frequency repetitive transcranial magnetic stimulation alleviates abnormal behavior in valproic acid rat model of autism through rescuing synaptic plasticity and inhibiting neuroinflammation
- Novel crosstalk mechanisms between GluA3 and Epac2 in synaptic plasticity and memory in Alzheimer's disease
- Estradiol receptors inhibit long-term potentiation in the dorsomedial striatum
- Electrophysiological Phenotypes of Hippocampal Synaptic and Network Functions in Cannabinoid Receptor 2 Knockout Mice
- Phospholipase Modulation of Synaptic Membrane Landscape: Driving Force Behind Memory Formation?
- Hyperexcitability and translational phenotypes in a preclinical model of SYNGAP1 mutations
- MDGA2 Constrains Glutamatergic Inputs Selectively onto CA1 Pyramidal Neurons to Optimize Neural Circuits for Plasticity, Memory, and Social Behavior
- Oligodendrocyte-derived LGI3 and its receptor ADAM23 organize juxtaparanodal Kv1 channel clustering for short-term synaptic plasticity
- Presynaptic structural and functional plasticity are coupled by convergent Rap1 signaling
- Early developmental deletion of forebrain Ank2 causes seizure-related phenotypes by reshaping the synaptic proteome
- Pathological Deficit of Cystatin B Impairs Synaptic Plasticity in EPM1 Human Cerebral Organoids
- Inhibitory and excitatory synaptic neuroadaptations in the diazepam tolerant brain
- Serotonin Signaling through Lipid Membranes
- Environmental enrichment improves social isolation-induced memory impairment: The possible role of ITSN1-Reelin-AMPA receptor signaling pathway
- SHP2 regulates GluA2 tyrosine phosphorylation required for AMPA receptor endocytosis and mGluR-LTD
- Tmod2 is a regulator of cocaine responses through control of striatal and cortical excitability, and drug-induced plasticity
- Targeted rescue of synaptic plasticity improves cognitive decline in sepsis-associated encephalopathy
- Enhanced hippocampal LTP but normal NMDA receptor and AMPA receptor function in a rat model of CDKL5 deficiency disorder
- NLRP3-GSDMD-dependent IL-1β secretion from microglia mediates learning and memory impairment in a chronic intermittent hypoxia-induced mouse model
- Trans-synaptic association of vesicular zinc transporter 3 and Shank3 supports synapse-specific dendritic spine structure and function in mouse auditory cortex
- A consistent map in the medial entorhinal cortex supports spatial memory
- Hippocampal synaptic failure is an early event in experimental parkinsonism with subtle cognitive deficit
- Synaptic plasticity at the dentate gyrus granule cell to somatostatin-expressing interneuron synapses supports object location memory
- Microglia at the Tripartite Synapse during Postnatal Development: Implications for Autism Spectrum Disorders and Schizophrenia
- Retromer Stabilization Improves Cognitive Function and Synaptic Plasticity in a Mouse Model of Down Syndrome
- Postnatal hypofunction of N-methyl-D-aspartate receptors alters perforant path synaptic plasticity and filtering and impairs dentate gyrus-mediated spatial discrimination
- Glial Sphingosine-mediated Epigenetic Regulation Stabilizes Synaptic Function in Drosophila Models of Alzheimer's Disease
- Intersectin deficiency impairs cortico-striatal neurotransmission and causes obsessive-compulsive behaviors in mice
- 5-HT4 receptor agonists treatment reduces tau pathology and behavioral deficit in the PS19 mouse model of tauopathy
- The interaction between KIF21A and KANK1 regulates dendritic morphology and synapse plasticity in neurons
- Resveratrol prevents cognitive deficits induced by sleep deprivation via modulating sirtuin 1 associated pathways in the hippocampus
- Mutations in FUS lead to synaptic dysregulation in ALS-iPSC derived neurons
- Shifting rules in a brain disorder
- Distinct SAP102 and PSD-95 nano-organization defines multiple types of synaptic scaffold protein domains at single synapses
- Comparative effects of the alcoholic extract of Terminalia chebula and crocin on stress‑induced anxiety‑like behavior and memory impairment in male rats
- Impaired cerebellar plasticity hypersensitizes sensory reflexes in SCN2A-associated ASD
- Short-term high-fat diet consumption impairs synaptic plasticity in the aged hippocampus via IL-1 signaling
- Systemic pharmacological suppression of neural activity reverses learning impairment in a mouse model of Fragile X syndrome
- The CHD family chromatin remodeling enzyme, Kismet, promotes both clathrin-mediated and activity-dependent bulk endocytosis
- Increased gene dosage of RFWD2 causes autistic-like behaviors and aberrant synaptic formation and function in mice
- Individual NMDA receptor GluN2 subunit signaling domains differentially regulate the postnatal maturation of hippocampal excitatory synaptic transmission and plasticity but not dendritic morphology
- Visualizing traumatic stress-induced structural plasticity in a medial amygdala pathway using mGRASP
- Genetic background determines synaptic phenotypes in Arid1b-mutant mice
- GR/Ahi1 regulates WDR68-DYRK1A binding and mediates cognitive impairment in prenatally stressed offspring
- mTORC1-mediated acquisition of reward-related representations by hippocampal somatostatin interneurons
- A novel inhibitory corticostriatal circuit that expresses mu opioid receptor-mediated synaptic plasticity
- Dysregulated glial genes in Alzheimer's disease are essential for homeostatic plasticity: Evidence from integrative epigenetic and single cell analyses
- SIK1 Downregulates Synaptic AMPA Receptors and Contributes to Cognitive Defects in Alzheimer's Disease