title: GABAB receptor-mediated frequency-dependent and circadian changes in synaptic plasticity modulate retinal input to the suprachiasmatic nucleus.
abstract: Light is the most important environmental signal that entrains the circadian clock located in the hypothalamic suprachiasmatic nucleus (SCN). The retinohypothalamic tract (RHT) was stimulated to simulate the light intensity-dependent discharges of intrinsically photosensitive retinal ganglion cells projecting axons to the hypothalamus. EPSCs were evoked by paired-pulse stimulation or by application of stimulus trains, and recorded from SCN neurons in rat brain slices. Initial release probability (Pr) and synaptic plasticity changes depended on the strength of GABAB receptor (GABABR)-mediated presynaptic inhibition and could be different at the same GABABR agonist concentration. Facilitation caused by frequency-dependent relief of GABABR-mediated inhibition was observed when the initial Pr was decreased to less than 15% of control during strong activation of presynaptic GABAB receptors by (±)baclofen (10 μm), GABA (2 mm) or by GABA uptake inhibitor nipecotic acid (5 mm). In contrast, short-term synaptic depression appeared during baclofen (10 μm) application when initial Pr was greater than 30% of control. Block of 4-aminopyridine-sensitive K(+) currents increased the amplitude and time constant of decay of evoked EPSCs (eEPSCs), and decreased the GABABR-mediated presynaptic inhibition. The GABAB receptor antagonist CGP55845 (3 μm) increased the eEPSCs amplitude 30% throughout the light-dark cycle. During light and dark phases the RHT inputs to 55% and 33% of recorded neurons, respectively, were under GABAB inhibitory control indicating that the tonic inhibition induced by local changes of endogenous GABA concentration contributes to the circadian variation of RHT transmitter release. We conclude that GABABR-mediated presynaptic inhibition decreased with increasing frequency and broadening of presynaptic action potentials, and depended on the sensitivity of RHT terminals to GABABR agonists, and diurnal changes of the extracellular GABA concentration around RHT axon terminals in the SCN.
authors: CROET, L606, Oregon Health & Science University, Portland, OR 97239-3098, USA. allenc@ohsu.edu
authors: Mykhaylo G
authors: MG
authors: Moldavan
authors: Charles N
authors: CN
authors: Allen
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002940:Circadian Rhythm / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009900:Optic Nerve / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000502:physiology*; D012160:Retina / Q000502:physiology*; D013493:Suprachiasmatic Nucleus / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D058786:GABA-B Receptor Agonists; D018080:Receptors, GABA-B; D001418:Baclofen
references: J Physiol. 1997 Mar 15;499 ( Pt 3):637-44
references: 9130160
references: J Comp Neurol. 2008 Feb 1;506(4):708-32
references: 18067149
references: J Biol Rhythms. 2006 Feb;21(1):21-32
references: 16461982
references: Brain Res. 1982 Aug 5;245(1):198-200
references: 6889453
references: Eur J Pharmacol. 1998 Apr 24;347(2-3):197-200
references: 9653881
references: Annu Rev Physiol. 2002;64:355-405
references: 11826273
references: Trends Neurosci. 2001 Jul;24(7):381-5
references: 11410267
references: J Anat. 2000 Jan;196 ( Pt 1):1-13
references: 10697283
references: J Neurosci. 2002 Nov 15;22(22):9661-7
references: 12427821
references: J Neurosci. 1999 May 15;19(10):4034-45
references: 10234032
references: J Neurosci. 1998 Mar 1;18(5):1913-22
references: 9465016
references: Neural Comput. 2001 Jan;13(1):69-85
references: 11177428
references: J Neurosci. 2012 Aug 15;32(33):11478-85
references: 22895730
references: Brain Res. 1997 Jun 13;759(2):181-9
references: 9221935
references: J Neurosci. 1998 May 1;18(9):3138-46
references: 9547222
references: J Neurosci. 2001 Mar 15;21(6):1857-67
references: 11245670
references: J Neurosci. 1998 Nov 1;18(21):9078-87
references: 9787011
references: J Neurophysiol. 2013 Apr;109(7):1876-89
references: 23343892
references: Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4699-704
references: 11296298
references: J Neurophysiol. 1998 Sep;80(3):1571-6
references: 9744963
references: FEBS Lett. 2002 Feb 13;512(1-3):303-7
references: 11852100
references: J Biol Rhythms. 1987 Spring;2(1):35-56
references: 2979650
references: Neurosci Lett. 1993 Jul 23;157(2):199-202
references: 8233053
references: J Neurosci. 1999 Jul 1;19(13):5185-94
references: 10377330
references: Brain Res. 1988 Apr 26;447(1):1-9
references: 2454699
references: J Neurophysiol. 2010 May;103(5):2390-9
references: 20220078
references: J Pharmacol Sci. 2008 Feb;106(2):301-9
references: 18270469
references: J Neurophysiol. 2006 Jun;95(6):3727-41
references: 16709723
references: J Neurochem. 1978 Aug;31(2):565-7
references: 671058
references: Eur J Neurosci. 2002 Dec;16(12):2469-74
references: 12492442
references: J Neurosci. 2000 Feb 1;20(3):889-98
references: 10648693
references: J Biol Chem. 2009 Dec 25;284(52):36453-36461
references: 19850918
references: J Neurosci. 2001 Dec 15;21(24):9608-18
references: 11739571
references: Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):8054-8
references: 11416164
references: J Physiol. 1954 Jun 28;124(3):560-73
references: 13175199
references: Vis Neurosci. 1992 Mar;8(3):219-30
references: 1372173
references: Brain Res Bull. 2004 Jul 15;63(6):531-5
references: 15249119
references: J Comp Neurol. 1999 Sep 6;411(4):683-92
references: 10421877
references: J Biol Rhythms. 1996 Dec;11(4):311-6
references: 8946258
references: J Neurosci. 1989 Aug;9(8):2858-65
references: 2549220
references: J Physiol. 1992 Feb;447:149-69
references: 1593445
references: Neuron. 1998 Jan;20(1):135-41
references: 9459449
references: Neuroscience. 1995 Feb;64(3):813-9
references: 7715789
references: J Neurophysiol. 2003 Sep;90(3):1438-48
references: 12750413
references: Neurosci Lett. 1997 Oct 10;235(1-2):98-100
references: 9389605
references: Neurosci Lett. 1993 Feb 5;150(1):112-6
references: 8097023
references: Brain Res. 1999 Jan 2;815(1):154-66
references: 9974136
references: Neuron. 1998 Apr;20(4):797-807
references: 9581770