ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Outwardly rectifying tonically active GABAA receptors in pyramidal cells modulate neuronal offset, not gain.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 118 citations in OpenAlex.
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- GABAAR-mediated tonic inhibition differentially modulates intrinsic excitability of VIP- and SST- expressing interneurons in layers 2/3 of the somatosensory cortex.Frontiers in cellular neuroscience · 2023Article
- Dysregulation of GABAA Receptor-Mediated Neurotransmission during the Auditory Cortex Critical Period in the Fragile X Syndrome Mouse Model.Cerebral cortex (New York, N.Y. : 1991) · 2021Article
- Therapeutic potential of alpha 5 subunit containing GABANeural regeneration research · 2021Article
- Diurnal properties of tonic and synaptic GABAJournal of neurophysiology · 2021Article
- The role of GABAergic signalling in neurodevelopmental disorders.Nature reviews. Neuroscience · 2021Review
- Pharmacological and Biophysical Characteristics of Picrotoxin-Resistant, δSubunit-Containing GABAFrontiers in synaptic neuroscience · 2021Article
- Extracellular GABA waves regulate coincidence detection in excitatory circuits.The Journal of physiology · 2020Article
- Tonic GABAThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- GABA-mediated tonic inhibition differentially modulates gain in functional subtypes of cortical interneurons.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Neuroactive Steroids Reverse Tonic Inhibitory Deficits in Fragile X Syndrome Mouse Model.Frontiers in molecular neuroscience · 2019Article
- Oxytocin Increases Phasic and Tonic GABAergic Transmission in CA1 Region of Mouse Hippocampus.Frontiers in cellular neuroscience · 2019Article
- Enhanced GABAergic Tonic Inhibition Reduces Intrinsic Excitability of Hippocampal CA1 Pyramidal Cells in Experimental Autoimmune Encephalomyelitis.Neuroscience · 2018Article
- Chemogenetic Isolation Reveals Synaptic Contribution of δ GABAThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Dendrite-targeting interneurons control synaptic NMDA-receptor activation via nonlinear α5-GABANature communications · 2018Article
- Feature Article: Selective modulation of tonically active GABAExperimental biology and medicine (Maywood, N.J.) · 2018Article
- Spontaneously opening GABACell death & disease · 2018Article
- Commonalities in epileptogenic processes from different acute brain insults: Do they translate?Epilepsia · 2018Review
9 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Hippocampal pyramidal cell excitability is regulated both by fast synaptic inhibition and by tonically active high-affinity extrasynaptic GABA(A) receptors. The impact of tonic inhibition on neuronal gain and offset, and thus on information processing, is unclear. Offset is altered by shunting inhibition, and the gain of a neuronal response to an excitatory input can be modified by changing the level of "background" synaptic noise. Therefore, tonic activation of GABA(A) receptors would be expected to modulate offset and, in addition, to alter gain through a shunting effect on synaptic noise. Here we show that tonically active GABA(A) receptors in CA1 pyramidal cells show marked outward rectification, while the peaks of IPSCs exhibit a linear current-voltage relationship. As a result, tonic GABA(A) receptor-mediated currents have a minimal effect upon subthreshold membrane potential variation due to synaptic noise, but predominantly affect neurons at spiking threshold. Consistent with this, tonic GABA(A) receptor-mediated currents in pyramidal cells exclusively affect offset and not gain. Modulation of tonically active GABA(A) receptors by fluctuations in extracellular GABA concentrations or neuromodulators acting on high-affinity receptors potentially provides a powerful mechanism to alter neuronal offset independently of neuronal gain.
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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.