GABA spillover activates postsynaptic GABA(B) receptors to control rhythmic hippocampal activity
- PMID: 10774734
- DOI: 10.1016/s0896-6273(00)81069-7
GABA spillover activates postsynaptic GABA(B) receptors to control rhythmic hippocampal activity
Abstract
In the hippocampus, interneurons provide synaptic inhibition via the transmitter GABA, which can activate GABA(A) and GABA(B) receptors (GABA(A)Rs and GABA(B)Rs). Generally, however, GABA released by a single interneuron activates only GABA(A)Rs on its targets, despite the abundance of GABA(B)RS. Here, I show that during hippocampal rhythmic activity, simultaneous release of GABA from several interneurons activates postsynaptic GABA(B)Rs and that block of GABA(B)Rs increases oscillation frequency. Furthermore, if GABA uptake is inhibited, even GABA released by a single interneuron is enough to activate GABA(B)Rs. This occurs also on cells not directly contacted by that interneuron, indicating that GABA has to overcome uptake and exit the synaptic cleft to reach GABA(B)RS. Thus, activation of extrasynaptic GABA(B)Rs by pooling of GABA is an important mechanism regulating hippocampal network activity.
Similar articles
-
Spontaneous release of GABA activates GABAB receptors and controls network activity in the neonatal rat hippocampus.J Neurophysiol. 1996 Aug;76(2):1036-46. doi: 10.1152/jn.1996.76.2.1036. J Neurophysiol. 1996. PMID: 8871218
-
Dual intracellular recordings and computational models of slow inhibitory postsynaptic potentials in rat neocortical and hippocampal slices.Neuroscience. 1999;92(4):1193-215. doi: 10.1016/s0306-4522(99)00021-4. Neuroscience. 1999. PMID: 10426478
-
GABAB receptor- and metabotropic glutamate receptor-dependent cooperative long-term potentiation of rat hippocampal GABAA synaptic transmission.J Physiol. 2003 Nov 15;553(Pt 1):155-67. doi: 10.1113/jphysiol.2003.049015. Epub 2003 Sep 8. J Physiol. 2003. PMID: 12963794 Free PMC article.
-
Do GABAA and GABAB inhibitory postsynaptic responses originate from distinct interneurons in the hippocampus?Can J Physiol Pharmacol. 1997 May;75(5):520-5. Can J Physiol Pharmacol. 1997. PMID: 9250387 Review.
-
Regulation of excitability by extrasynaptic GABA(A) receptors.Results Probl Cell Differ. 2008;44:29-48. doi: 10.1007/400_2007_030. Results Probl Cell Differ. 2008. PMID: 17671772 Review.
Cited by
-
Somatostatin Interneurons Recruit Pre- and Postsynaptic GABAB Receptors in the Adult Mouse Dentate Gyrus.eNeuro. 2024 Aug 19;11(8):ENEURO.0115-24.2024. doi: 10.1523/ENEURO.0115-24.2024. Print 2024 Aug. eNeuro. 2024. PMID: 39084907 Free PMC article.
-
Extrasynaptic δGABAA receptors mediate resistance to migraine-like phenotype in rats.J Headache Pain. 2024 May 10;25(1):75. doi: 10.1186/s10194-024-01777-4. J Headache Pain. 2024. PMID: 38724972 Free PMC article.
-
GABAB Receptors Tonically Inhibit Motoneurons and Neurotransmitter Release from Descending and Primary Afferent Fibers.Life (Basel). 2023 Aug 20;13(8):1776. doi: 10.3390/life13081776. Life (Basel). 2023. PMID: 37629633 Free PMC article.
-
CGP7930 - An allosteric modulator of GABABRs, GABAARs and inwardly-rectifying potassium channels.Neuropharmacology. 2023 Nov 1;238:109644. doi: 10.1016/j.neuropharm.2023.109644. Epub 2023 Jul 6. Neuropharmacology. 2023. PMID: 37422181 Free PMC article.
-
Volume-transmitted GABA waves pace epileptiform rhythms in the hippocampal network.Curr Biol. 2023 Apr 10;33(7):1249-1264.e7. doi: 10.1016/j.cub.2023.02.051. Epub 2023 Mar 14. Curr Biol. 2023. PMID: 36921605 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources