ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Alpha5GABAA receptor activity sets the threshold for long-term potentiation and constrains hippocampus-dependent memory.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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96 citing papers in PubMed.
- Effects of the Selective α5-GABAAR Antagonist S44819 on Excitability in the Human Brain: A TMS-EMG and TMS-EEG Phase I Study.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Trial
- The role of GABANeuroscience and biobehavioral reviews · 2026Review
- GABACellular and molecular neurobiology · 2026Review
- Restoration of Extrasynaptic/Synaptic GABANeuroscience bulletin · 2026Article
- The rise and deceleration of neuronal excitability in aging and Alzheimer's disease: Mechanisms, implications, and therapeutic targets.Ageing research reviews · 2026Review
- The NMDA receptor subunit GluN2D is a potential target for rapid antidepressant action.Nature communications · 2025Article
- Electroencephalography Biomarkers of α5-GABA Positive Allosteric Modulators in Rodents.Biological psychiatry global open science · 2025Article
- Review
- Domain-selective and sex-dependent regulation of learning and memory in mice by GIRK channel activity in CA1 pyramidal neurons of the dorsal hippocampus.Learning & memory (Cold Spring Harbor, N.Y.) · 2024Article
- Sevoflurane-induced overexpression of extrasynaptic α5-GABAAging cell · 2024Article
- Enhancing cognitive recovery in chronic traumatic brain injury through simultaneous allosteric modulation of α7 nicotinic acetylcholine and α5 GABAExperimental neurology · 2024Article
- Haploinsufficiency of GABAThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- GABAProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Genetics and Molecular Biology of Memory Suppression.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024Review
- IL-1β, the first piece to the puzzle of sepsis-related cognitive impairment?Frontiers in neuroscience · 2024Review
- Long-term α5 GABA A receptor negative allosteric modulator treatment reduces NMDAR-mediated neuronal excitation and maintains basal neuronal inhibition.Neuropharmacology · 2023Article
- Impact of Developmental Changes of GABAInternational journal of molecular sciences · 2023Article
- Ablation ofGenes · 2023Article
- Bidirectional plasticity of GABAergic tonic inhibition in hippocampal somatostatin- and parvalbumin-containing interneurons.Frontiers in cellular neuroscience · 2023Article
- Sleep and wake cycles dynamically modulate hippocampal inhibitory synaptic plasticity.PLoS biology · 2022Article
36 more citing papers are in PubMed but not listed here.
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6 authors.
Funding
Abstract
Synaptic plasticity, which is the neuronal substrate for many forms of hippocampus-dependent learning, is attenuated by GABA type A receptor (GABA(A)R)-mediated inhibition. The prevailing notion is that a synaptic or phasic form of GABAergic inhibition regulates synaptic plasticity; however, little is known about the role of GABA(A)R subtypes that generate a tonic or persistent inhibitory conductance. We studied the regulation of synaptic plasticity by alpha5 subunit-containing GABA(A)Rs (alpha5GABA(A)Rs), which generate a tonic inhibitory conductance in CA1 pyramidal neurons using electrophysiological recordings of field and whole-cell potentials in hippocampal slices from both wild-type and null mutant mice for the alpha5 subunit of the GABA(A)R (Gabra5(-/-) mice). In addition, the strength of fear-associated memory was studied. The results showed that alpha5GABA(A)R activity raises the threshold for induction of long-term potentiation in a highly specific band of stimulation frequencies (10-20 Hz) through mechanisms that are predominantly independent of inhibitory synaptic transmission. The deletion or pharmacological inhibition of alpha5GABA(A)Rs caused no change in baseline membrane potential or input resistance but increased depolarization during 10 Hz stimulation. The encoding of hippocampus-dependent memory was regulated by alpha5GABA(A)Rs but only under specific conditions that generate moderate but not robust forms of fear-associated learning. Thus, under specific conditions, alpha5GABA(A)R activity predominates over synaptic inhibition in modifying the strength of both synaptic plasticity in vitro and certain forms of memory in vivo.
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