ArticlePLoS genetics2008
A PI3-kinase-mediated negative feedback regulates neuronal excitability.
Article in PLoS genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 55 citations in OpenAlex.
- The maternal vGluT2 and embryonic mGluR3 signaling relay system controls offspring wing dimorphism in pea aphid.iScience · 2025Article
- The Importance of Phosphoinositide 3-Kinase in Neuroinflammation.International journal of molecular sciences · 2024Review
- Metabotropic glutamate receptors (mGluRs) in epileptogenesis: an update on abnormal mGluRs signaling and its therapeutic implications.Neural regeneration research · 2024Review
- Implication of sestrin3 in epilepsy and its comorbidities.Brain communications · 2021Article
- Insulin and Leptin/Upd2 Exert Opposing Influences on Synapse Number in Fat-Sensing Neurons.Cell metabolism · 2020Article
- Dscam2 suppresses synaptic strength through a PI3K-dependent endosomal pathway.The Journal of cell biology · 2020Article
- Downregulation of Astrocytic Kir4.1 Potassium Channels Is Associated with Hippocampal Neuronal Hyperexcitability in Type 2 Diabetic Mice.Brain sciences · 2020Article
- The TOR Pathway at the Neuromuscular Junction: More Than a Metabolic Player?Frontiers in molecular neuroscience · 2020Review
- FOXO Regulates Neuromuscular Junction Homeostasis DuringFrontiers in aging neuroscience · 2020Article
- Keeping Neurons Young and Foxy: FoxOs Promote Neuronal Plasticity.Trends in genetics : TIG · 2018Review
- Drosophila Studies on Autism Spectrum Disorders.Neuroscience bulletin · 2017Review
- Differential effects of myostatin deficiency on motor and sensory axons.Muscle & nerve · 2017Article
- Acute Fasting Regulates Retrograde Synaptic Enhancement through a 4E-BP-Dependent Mechanism.Neuron · 2016Article
- Article
- The effects of ER morphology on synaptic structure and function in Drosophila melanogaster.Journal of cell science · 2016Article
- Odorant Stimulation Promotes Survival of Rodent Olfactory Receptor Neurons via PI3K/Akt Activation and Bcl-2 Expression.Molecules and cells · 2015Article
- Lowered insulin signalling ameliorates age-related sleep fragmentation in Drosophila.PLoS biology · 2014Article
- Homeostatic plasticity at the Drosophila neuromuscular junction.Neuropharmacology · 2014Review
- Insulin signaling regulates neurite growth during metamorphic neuronal remodeling.Biology open · 2014Article
- Drosophila neuroligin 1 regulates synaptic growth and function in response to activity and phosphoinositide-3-kinase.Molecular and cellular neurosciences · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Use-dependent downregulation of neuronal activity (negative feedback) can act as a homeostatic mechanism to maintain neuronal activity at a particular specified value. Disruption of this negative feedback might lead to neurological pathologies, such as epilepsy, but the precise mechanisms by which this feedback can occur remain incompletely understood. At one glutamatergic synapse, the Drosophila neuromuscular junction, a mutation in the group II metabotropic glutamate receptor gene (DmGluRA) increased motor neuron excitability by disrupting an autocrine, glutamate-mediated negative feedback. We show that DmGluRA mutations increase neuronal excitability by preventing PI3 kinase (PI3K) activation and consequently hyperactivating the transcription factor Foxo. Furthermore, glutamate application increases levels of phospho-Akt, a product of PI3K signaling, within motor nerve terminals in a DmGluRA-dependent manner. Finally, we show that PI3K increases both axon diameter and synapse number via the Tor/S6 kinase pathway, but not Foxo. In humans, PI3K and group II mGluRs are implicated in epilepsy, neurofibromatosis, autism, schizophrenia, and other neurological disorders; however, neither the link between group II mGluRs and PI3K, nor the role of PI3K-dependent regulation of Foxo in the control of neuronal excitability, had been previously reported. Our work suggests that some of the deficits in these neurological disorders might result from disruption of glutamate-mediated homeostasis of neuronal excitability.
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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.