Nicotinic receptor-mediated biphasic effect on neuronal excitability in chick lateral spiriform neurons.
Local neuronal circuits integrate synaptic information with different excitatory or inhibitory time windows. Here we report that activation of nicotinic acetylcholine receptors (nAChRs) leads to biphasic effects on excitability in chick lateral spiriform (SPL) neurons during whole cell recordings in brain slices. Carbachol (100 microM in the presence of 1 microM atropine) produced an initial short-term increase in the firing rates of SPL neurons (125+/-14% of control) that was mediated by postsynaptic nAChRs. However, after 3 min exposure to nicotinic agonists, the firing rate measured during an 800 ms depolarizing pulse declined to 19+/-7% (100 microM carbachol) or 26+/-8% (10 microM nicotine) of the control rate and remained decreased for 10-20 min after washout of the agonists. Similarly, after 60 s of electrically-stimulated release of endogenous acetylcholine (ACh) from cholinergic afferent fibers, there was a marked reduction (45+/-5% of control) in firing rates in SPL neurons. All of these effects were blocked by the nAChR antagonist dihydro-beta-erythroidine (30 microM). The inhibitory effect was not observed in Ca(2+)-free buffer. The nAChR-mediated inhibition depended on active G-proteins in SPL neurons and was prevented by the GABA(B) receptor antagonist phaclofen (200 microM), while the GABA(B) receptor agonist baclofen (10 microM) decreased firing rate in SPL neurons to 13+/-1% of control. The inhibitory response thus appears to be due to a nAChR-mediated enhancement of presynaptic GABA release, which then activates postsynaptic GABA(B) receptors. In conclusion, activation of nAChRs in the SPL initiates a limited time window for an excitatory period, after which a prolonged inhibitory effect turns off this window. The prolonged inhibitory effect may serve to protect SPL neurons from excessive excitation.
Liu
Y-B
YB
Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, 2300 Eye Street, Northwest, Washington, DC 20037, USA. yliu@usuhs.mil
Guo
J-Z
JZ
Chiappinelli
V A
VA
D000200:Action Potentials / Q000187:drug effects / Q000528:radiation effects; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000166:cytology* / Q000196:embryology; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002642:Chick Embryo; D018679:Cholinergic Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009538:Nicotine / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology*; D013997:Time Factors
D018679:Cholinergic Agonists; D018756:GABA Antagonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C052329:phaclofen; D009538:Nicotine; D002217:Carbachol; D001418:Baclofen; D002118:Calcium
J Neurophysiol. 1998 Aug;80(2):493-503
9705445
Neuroscience. 1998 Sep;86(1):211-20
9692755
J Neurosci. 1998 Oct 15;18(20):8228-35
9763468
J Neurochem. 1998 Dec;71(6):2439-46
9832142
J Neurophysiol. 1999 Feb;81(2):447-54
10036250
J Physiol. 1999 Mar 15;515 ( Pt 3):769-76
10066903
J Neurosci. 1999 Apr 1;19(7):2693-705
10087082
J Neurosci. 1999 May 15;19(10):3701-10
10234002
J Neurophysiol. 1999 Jun;81(6):2875-83
10368404
J Neurosci. 1999 Sep 15;19(18):7804-11
10479683
Trends Neurosci. 2005 Jul;28(7):353-63
15935486
J Neurosci. 2005 Jun 29;25(26):6084-91
15987938
Brain Res Bull. 2005 Sep 15;66(4-6):317-31
16144608
Neuroscience. 2006 Oct 13;142(2):595-606
16887273
Annu Rev Pharmacol Toxicol. 2007;47:699-729
17009926
Nat Neurosci. 1999 Dec;2(12):1098-105
10570487
Neuropharmacology. 1999 Nov;38(11):1743-53
10587090
Nature. 2000 Nov 30;408(6812):584-8
11117745
J Neurosci. 2001 Apr 15;21(8):2861-77
11306638
Nicotine Tob Res. 2001 Aug;3(3):203-23
11506765
Nat Neurosci. 2001 Nov;4 Suppl:1207-14
11687831
J Neurophysiol. 2001 Dec;86(6):3043-55
11731559
FASEB J. 2002 Mar;16(3):423-5
11790724
Neuron. 2002 Mar 14;33(6):905-19
11906697
Neuroscience. 2002;110(3):459-73
11906786
Nature. 2002 Mar 28;416(6879):433-8
11919633
J Neurochem. 2002 May;81(4):853-8
12065644
Science. 2002 Sep 20;297(5589):2070-3
12242447
Neuroscience. 2002;115(1):137-44
12401328
Trends Pharmacol Sci. 2004 Jun;25(6):317-24
15165747
Nature. 2004 Jun 17;429(6993):717-23
15170216
J Physiol. 1970 Oct;210(3):651-67
5499817
Brain Res. 1975 Jan 24;84(1):1-22
163121
Science. 1981 May 1;212(4494):555-7
6782676
J Physiol. 1984 Sep;354:319-31
6434729
Brain Res. 1985 Jul 22;339(1):186-90
3896401
Nature. 1989 Aug 31;340(6236):715-8
2475782
J Physiol. 1989 Feb;409:171-90
2585290
J Physiol. 1989 Sep;416:111-22
2558172
Neuron. 1990 Sep;5(3):307-15
2400604
J Neurosci. 1992 Jan;12(1):278-89
1309574
J Neurophysiol. 1993 Mar;69(3):1000-4
8385186
Neuroscience. 1994 Apr;59(3):689-98
8008213
J Neurosci. 1994 Sep;14(9):5514-24
8083751
Neuroscience. 1995 Jul;67(2):293-300
7675170
Neuron. 1996 May;16(5):905-8
8630247
J Pharmacol Exp Ther. 1996 Jun;277(3):1733-43
8667245
Neuron. 1996 Jun;16(6):1077-85
8663984
Neuroscience. 1996 May;72(2):545-55
8737423
J Neurophysiol. 1996 Aug;76(2):651-67
8871189
Nature. 1997 Nov 27;390(6658):401-4
9389479
Brain Res Brain Res Rev. 1998 May;26(2-3):198-216
9651527
Neurotoxicology. 1998 Aug-Oct;19(4-5):511-4
9745905