title: Acting locally but sensing globally: impact of GABAergic synaptic plasticity on phasic and tonic inhibition in the thalamus.
abstract: We have discovered that adult thalamocortical relay neurones exhibit a sustained enhancement of synaptic inhibition triggered by transient action potential firing of a single thalamic relay neurone. The sustained activity-dependent increase in IPSC frequency (+48.3 +/- 11.4%, n = 32) was blocked by chelating calcium inside an individual cell, by scavenging nitric oxide or by blocking NMDA receptor activation in the thalamus. Surprisingly, the tonic inhibition that is known to result from extrasynaptic GABA(A) receptor activation in these cells was unaffected by this local form of plasticity. However, tonic inhibition was increased (+131.9 +/- 56.5%, n = 13) following widespread changes in GABA release across the thalamus. These data suggest that thalamocortical sleep-state oscillations requiring membrane hyperpolarization will be influenced by global sensing of GABA release acting through extrasynaptic GABA(A) receptors. In contrast, local changes in GABA release of the type observed following this novel form of activity-dependent plasticity will influence local integration of sensory information without changing levels of tonic inhibition.
authors.affiliation: Biophysics Section, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: Damian P
authors.initials: DP
authors.lastname: Bright
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Brickley
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000502:physiology*; D013788:Thalamus / Q000166:cytology* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid; D010396:Penicillamine; D002118:Calcium
references.citation: Nat Neurosci. 2007 Apr;10(4):469-77
references.pmid: 17351635
references.citation: J Neurosci. 2005 Dec 14;25(50):11513-20
references.pmid: 16354909
references.citation: Neuroscience. 2002;110(3):395-401
references.pmid: 11906781
references.citation: J Physiol. 2007 Aug 1;582(Pt 3):1163-78
references.pmid: 17525114
references.citation: J Neurosci. 2003 Aug 20;23(20):7642-6
references.pmid: 12930803
references.citation: J Neurosci. 2005 Dec 14;25(50):11553-63
references.pmid: 16354913
references.citation: Trends Neurosci. 2005 Jun;28(6):317-24
references.pmid: 15927688
references.citation: J Neurophysiol. 2003 Mar;89(3):1378-86
references.pmid: 12626617
references.citation: J Comp Neurol. 2008 May 10;508(2):264-85
references.pmid: 18314907
references.citation: Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15230-5
references.pmid: 17005728
references.citation: J Neurophysiol. 2005 Dec;94(6):4491-501
references.pmid: 16162835
references.citation: Nat Neurosci. 2001 Aug;4(8):803-12
references.pmid: 11477426
references.citation: Neuron. 2002 Feb 14;33(4):625-33
references.pmid: 11856535
references.citation: Eur J Neurosci. 2007 Mar;25(6):1893-9
references.pmid: 17408425
references.citation: J Neurophysiol. 2007 May;97(5):3386-95
references.pmid: 17376843
references.citation: J Neurosci. 2006 Dec 27;26(52):13443-53
references.pmid: 17192427
references.citation: Nature. 2007 Apr 26;446(7139):1086-90
references.pmid: 17460674
references.citation: J Physiol. 1996 Dec 15;497 ( Pt 3):753-9
references.pmid: 9003560
references.citation: J Physiol. 2003 Apr 1;548(Pt 1):97-110
references.pmid: 12588900
references.citation: Nature. 2002 Jun 20;417(6891):854-8
references.pmid: 12075353
references.citation: Eur J Neurosci. 1997 Mar;9(3):533-48
references.pmid: 9104595
references.citation: Nature. 2001 Jan 4;409(6816):88-92
references.pmid: 11343119
references.citation: Nat Neurosci. 2005 Jun;8(6):797-804
references.pmid: 15895085
references.citation: Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14439-44
references.pmid: 14623958
references.citation: Neuroscience. 1995 May;66(1):133-41
references.pmid: 7637863
references.citation: Nat Rev Neurosci. 2005 Mar;6(3):215-29
references.pmid: 15738957
references.citation: J Neurosci. 2007 Mar 7;27(10):2560-9
references.pmid: 17344393