ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Sapap3 deletion anomalously activates short-term endocannabinoid-mediated synaptic plasticity.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed.
- Evaluation of hippocampal DLGAP2 overexpression on cognition, synaptic function, and dendritic spine structure in a translationally relevant AD mouse model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Hyperactivity of indirect pathway-projecting spiny projection neurons promotes compulsive behavior.Nature communications · 2024Article
- Informational Analysis and Prediction of Obsessive-Compulsive Disorder Pathogenesis.Psychiatry investigation · 2024Article
- Pathway-specific alterations in striatal excitability and cholinergic modulation in a SAPAP3 mouse model of compulsive motor behavior.Cell reports · 2023Article
- Spinophilin Limits Metabotropic Glutamate Receptor 5 Scaffolding to the Postsynaptic Density and Cell Type Specifically Mediates Excessive Grooming.Biological psychiatry · 2023Article
- Review
- Cocaine restricts nucleus accumbens feedforward drive through a monoamine-independent mechanism.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Optogenetic inhibition of indirect pathway neurons in the dorsomedial striatum reduces excessive grooming in Sapap3-knockout mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Ketamine increases activity of a fronto-striatal projection that regulates compulsive behavior in SAPAP3 knockout mice.Nature communications · 2021Article
- Cannabinoid type 1 receptors in A2a neurons contribute to cocaine-environment association.Psychopharmacology · 2021Article
- Article
- Article
- Modulation of dendritic spines by protein phosphatase-1.Advances in pharmacology (San Diego, Calif.) · 2021Review
- Sapap3 deletion causes dynamic synaptic density abnormalities: a longitudinal [EJNMMI research · 2020Article
- Projection-specific deficits in synaptic transmission in adult Sapap3-knockout mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Article
- The sociability spectrum: evidence from reciprocal genetic copy number variations.Molecular autism · 2020Review
- Cataloguing and Selection of mRNAs Localized to Dendrites in Neurons and Regulated by RNA-Binding Proteins in RNA Granules.Biomolecules · 2020Review
- Multiple Rare Risk Coding Variants in Postsynaptic Density-Related Genes Associated With Schizophrenia Susceptibility.Frontiers in genetics · 2020Article
- Neural Mechanisms Underlying Repetitive Behaviors in Rodent Models of Autism Spectrum Disorders.Frontiers in cellular neuroscience · 2020Review
- Aberrant habit formation in the Sapap3-knockout mouse model of obsessive-compulsive disorder.Scientific reports · 2019Article
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Authors and funding
6 authors.
Funding
Abstract
Retrograde synaptic signaling by endocannabinoids (eCBs) is a widespread mechanism for activity-dependent inhibition of synaptic strength in the brain. Although prevalent, the conditions for eliciting eCB-mediated synaptic depression vary among brain circuits. As yet, relatively little is known about the molecular mechanisms underlying this variation, although the initial signaling events are likely dictated by postsynaptic proteins. SAP90/PSD-95-associated proteins (SAPAPs) are a family of postsynaptic proteins unique to excitatory synapses. Using Sapap3 knock-out (KO) mice, we find that, in the absence of SAPAP3, striatal medium spiny neuron (MSN) excitatory synapses exhibit eCB-mediated synaptic depression under conditions that do not normally activate this process. The anomalous synaptic plasticity requires type 5 metabotropic glutamate receptors (mGluR5s), which we find are dysregulated in Sapap3 KO MSNs. Both surface expression and activity of mGluR5s are increased in Sapap3 KO MSNs, suggesting that enhanced mGluR5 activity may drive the anomalous synaptic plasticity. In direct support of this possibility, we find that, in wild-type (WT) MSNs, pharmacological enhancement of mGluR5 by a positive allosteric modulator is sufficient to reproduce the increased synaptic depression seen in Sapap3 KO MSNs. The same pharmacologic treatment, however, fails to elicit further depression in KO MSNs. Under conditions that are sufficient to engage eCB-mediated synaptic depression in WT MSNs, Sapap3 deletion does not alter the magnitude of the response. These results identify a role for SAPAP3 in the regulation of postsynaptic mGluRs and eCB-mediated synaptic plasticity. SAPAPs, through their effect on mGluR activity, may serve as regulatory molecules gating the threshold for inducing eCB-mediated synaptic plasticity.
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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 OpenQuestion graph.