ArticleBehavioural brain research2012
Genetic reduction of muscarinic M4 receptor modulates analgesic response and acoustic startle response in a mouse model of fragile X syndrome (FXS).
Article in Behavioural brain research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 57 citations in OpenAlex.
- Brain circuitry, behavior, and cognition: A randomized placebo-controlled trial of donepezil in fragile X syndrome.Journal of psychopharmacology (Oxford, England) · 2019Trial
- Neonatal expression of human FMRP isoform corrects cortical deficits and improves behavior in a mouse model of fragile X syndrome.Molecular therapy. Nucleic acids · 2026Article
- Early Developmental Characterization of Gap-Induced Prepulse Inhibition and Habituation of Auditory Startle Response in a Fragile X Syndrome Mouse Model.Developmental neuroscience · 2026Article
- Standardized Pipeline for Metabolism and Cognition in GO-DS21 Mouse Model: Investigating Down Syndrome Comorbidities.Current protocols · 2026Article
- Dysfunctional neural dynamics associated with sensory phenotypes in Fragile X syndrome: insights from mouse models.Journal of neurodevelopmental disorders · 2025Review
- ErbB inhibition rescues nigral dopamine neuron hyperactivity and repetitive behaviors in a mouse model of fragile X syndrome.Molecular psychiatry · 2025Article
- Behavioral benefits of GSK-3β inhibition and state-dependent microtubule signatures in theFrontiers in neuroscience · 2025Article
- Understanding pathophysiology in fragile X syndrome: a comprehensive review.Neurogenetics · 2024Review
- Ketogenic Diet Affects Sleep Architecture in C57BL/6J Wild Type and Fragile X Mice.International journal of molecular sciences · 2023Article
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- Mouse models of fragile X-related disorders.Disease models & mechanisms · 2023Review
- Robust and replicable measurement for prepulse inhibition of the acoustic startle response.Molecular psychiatry · 2021Article
- Hyperactive ACC-MDT Pathway Suppresses Prepulse Inhibition in Mice.Schizophrenia bulletin · 2021Article
- Mechanisms underlying auditory processing deficits in Fragile X syndrome.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Review
- Audiogenic Seizures in theThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- A single early-life seizure results in long-term behavioral changes in the adult Fmr1 knockout mouse.Epilepsy research · 2019Article
- Human Models Are Needed for Studying Human Neurodevelopmental Disorders.American journal of human genetics · 2018Review
- Pharmacological Rescue of Hippocampal Fear Learning Deficits in Fragile X Syndrome.Molecular neurobiology · 2018Article
- Total RNA Sequencing of Rett Syndrome Autopsy Samples Identifies the MThe Journal of pharmacology and experimental therapeutics · 2018Article
- Activation of Serotonin 5-HTFrontiers in molecular neuroscience · 2018Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
introductionThe G-protein coupled muscarinic acetylcholine receptors, widely expressed in the CNS, have been implicated in fragile X syndrome (FXS). Recent studies have reported an overactive signaling through the muscarinic receptors in the Fmr1KO mouse model. Hence, it was hypothesized that reducing muscarinic signaling might modulate behavioral phenotypes in the Fmr1KO mice. Pharmacological studies from our lab have provided evidence for this hypothesis, with subtype-preferring muscarinic M1 and M4 receptor antagonists modulating select behaviors in the Fmr1KO mice. Since the pharmacological antagonists were not highly specific, we investigated the specific role of M4 receptors in the Fmr1KO mouse model, using a genetic approach.
methodsWe created a double mutant heterozygous for the M4 receptor gene and hemizygous for the Fmr1 gene and examined the mutants on various behaviors. Each animal was tested on a behavior battery comprising of open-field activity (activity), light-dark (anxiety), marble burying (perseverative behavior), prepulse inhibition (sensorimotor gating), rotarod (motor coordination), passive avoidance (learning and memory) and hotplate (analgesia). Animals were also tested on the audiogenic seizure protocol and testis weights were measured.
resultsReduction of M4 receptor expression in the heterozygotes completely rescued the analgesic response and partly rescued the acoustic startle response phenotype in the Fmr1KO mice. However, no modulation was observed in a number of behaviors including learning and memory, activity, perseverative behavior and audiogenic seizures.
conclusionReducing M4 receptor signaling altered only select behavioral phenotypes in the Fmr1KO mouse model, suggesting that other targets are involved in the modulation of fragile X behaviors.
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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 OpenQuestion graph.