Plasticity at glycinergic synapses in dorsal cochlear nucleus of rats with behavioral evidence of tinnitus.
Fifteen percent to 35% of the United States population experiences tinnitus, a subjective "ringing in the ears". Up to 10% of those afflicted report severe and disabling symptoms. Tinnitus was induced in rats using unilateral, 1 h, 17 kHz-centered octave-band noise (116 dB SPL) and assessed using a gap-startle method. The dorsal cochlear nucleus (DCN) is thought to undergo plastic changes suggestive of altered inhibitory function during tinnitus development. Exposed rats showed near pre-exposure auditory brainstem response (ABR) thresholds for clicks and all tested frequencies 16 weeks post-exposure. Sound-exposed rats showed significantly worse gap detection at 24 and 32 kHz 16 weeks following sound exposure, suggesting the development of chronic, high frequency tinnitus. Message and protein levels of alpha(1-3,) and beta glycine receptor subunits (GlyRs), and the anchoring protein, gephyrin, were measured in DCN fusiform cells 4 months following sound exposure. Rats with evidence of tinnitus showed significant GlyR alpha(1) protein decreases in the middle and high frequency regions of the DCN while alpha(1) message levels were paradoxically increased. Gephyrin levels showed significant tinnitus-related increases in sound-exposed rats suggesting intracellular receptor trafficking changes following sound exposure. Consistent with decreased alpha(1) subunit protein levels, strychnine binding studies showed significant tinnitus-related decreases in the number of GlyR binding sites, supporting tinnitus-related changes in the number and/or composition of GlyRs. Collectively, these findings suggest the development of tinnitus is likely associated with functional GlyR changes in DCN fusiform cells consistent with previously described behavioral and neurophysiologic changes. Tinnitus related GlyR changes could provide a unique receptor target for tinnitus pharmacotherapy or blockade of tinnitus initiation.
Wang
H
H
Department of Pharmacology, Southern Illinois University School of Medicine, PO Box 19629, Springfield, IL 62794-9629, USA.
Brozoski
T J
TJ
Turner
J G
JG
Ling
L
L
Parrish
J L
JL
Hughes
L F
LF
Caspary
D M
DM
D000161:Acoustic Stimulation; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002908:Chronic Disease; D017626:Cochlear Nucleus / Q000503:physiopathology*; D016057:Evoked Potentials, Auditory, Brain Stem; D005998:Glycine / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D011571:Psychoacoustics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D018009:Receptors, Glycine / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D013997:Time Factors; D014012:Tinnitus / Q000503:physiopathology*
D002352:Carrier Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D018009:Receptors, Glycine; C073441:gephyrin; C113965:glycine receptor alpha3 subunit; D005998:Glycine
Eur J Biochem. 1990 Nov 26;194(1):1-8
2174770
Int J Audiol. 2003 Jan;42(1):4-9
12564510
Hear Res. 2003 Jun;180(1-2):28-38
12782350
J Comp Neurol. 1997 Sep 1;385(3):405-14
9300767
Brain Res Bull. 1985 Nov;15(5):473-86
2998565
Exp Brain Res. 2003 Dec;153(4):649-54
14508632
Ann N Y Acad Sci. 1992 Nov 21;663:48-62
1482093
Hear Res. 2000 Jan;139(1-2):13-30
10601709
J Acoust Soc Am. 1991 Jul;90(1):155-63
1880283
Hear Res. 1989 Apr;38(3):221-8
2540135
Laryngoscope. 2006 Jun;116(6):970-5
16735910
Hear Res. 1991 Jan;51(1):11-28
1672865
Otolaryngol Head Neck Surg. 1999 Oct;121(4):457-62
10504604
Cell Tissue Res. 2006 Nov;326(2):535-40
16807723
Trends Neurosci. 2008 May;31(5):257-64
18403029
Scand Audiol Suppl. 1998;48:75-86
9505300
Psychosomatics. 2006 Jul-Aug;47(4):282-8
16844885
J Neurochem. 1987 Jul;49(1):128-37
3585325
Mol Pharmacol. 1996 Aug;50(2):402-6
8700149
Braz J Otorhinolaryngol. 2005 Jul-Aug;71(4):427-31
16446955
Hear Res. 1999 Feb;128(1-2):70-4
10082285
Noise Health. 2004 Oct-Dec;7(25):29-40
15703147
Peptides. 2007 Feb;28(2):464-74
17194506
Exp Neurol. 1998 Dec;154(2):473-88
9878183
Brain Res. 1992 Sep 11;590(1-2):95-108
1330217
Hear Res. 2000 Sep;147(1-2):125-36
10962179
Hear Res. 2006 Jun-Jul;216-217:207-15
16644158
J Neurochem. 2005 Jun;93(5):1069-86
15934929
Mech Ageing Dev. 2002 Jan;123(2-3):207-13
11718813
Ann N Y Acad Sci. 2000 Jun;908:143-54
10911955
J Neurochem. 1999 Mar;72(3):1323-6
10037506
Neuroscience. 2000;98(1):149-56
10858621
J Neurosci. 1983 Jan;3(1):237-42
6822858
J Acoust Soc Am. 1968 Dec;44(6):1503-6
5702023
Gen Hosp Psychiatry. 1988 Jul;10(4):285-91
3417130
Nat Rev Neurosci. 2001 Apr;2(4):240-50
11283747
EMBO Rep. 2005 Jan;6(1):22-7
15643447
Behav Neurosci. 2005 Jun;119(3):734-42
15998194
Neurosci Lett. 1992 Sep 14;144(1-2):19-24
1436702
Laryngoscope. 1998 Jan;108(1 Pt 1):26-31
9432062
Neurosci Lett. 2004 Jan 23;355(1-2):121-5
14729250
Exp Gerontol. 2000 Mar;35(2):119-31
10767573
Exp Gerontol. 1996 Jan-Apr;31(1-2):33-47
8706803
J Neurochem. 2006 Jun;97(6):1600-10
16805771
Brain Res. 1987 Aug 11;417(2):273-82
3651816
Nat Neurosci. 2001 Mar;4(3):253-60
11224541
Jpn J Physiol. 1994;44 Suppl 2:S97-9
7752563
Traffic. 2006 Dec;7(12):1604-6
17054759
Neuroscience. 2005;132(4):1103-13
15857714
Drugs Aging. 2004;21(5):297-305
15040757
Neurochem Res. 1989 Jun;14(6):563-70
2761675
Biol Cell. 2007 Jun;99(6):297-309
17504238
Hear Res. 1988 Nov;36(2-3):181-9
3209491
Prog Brain Res. 2007;166:19-35
17956768
J Comp Neurol. 1997 Mar 17;379(3):455-65
9067836
Neurosci Lett. 1998 Jul 10;250(3):197-200
9708866
Audiology. 2001 May-Jun;40(3):133-40
11465295
Cell Mol Life Sci. 2001 May;58(5-6):760-93
11437237
Hear Res. 2006 Jun-Jul;216-217:224-34
16469461
J Neurosci Res. 2007 May 15;85(7):1489-98
17393482
Prog Brain Res. 2007;166:89-106
17956775
Hear Res. 2005 Aug;206(1-2):227-36
16081010
J Physiol Paris. 1994;88(4):243-8
7874085
Otolaryngol Clin North Am. 2003 Apr;36(2):383-8
12856305
Audiol Neurootol. 2003 May-Jun;8(3):129-39
12679624
Neuroscience. 1995 Aug;67(3):713-9
7675197
Cell Cycle. 2006 Jun;5(12):1292-6
16760669
Brain Res. 2008 Apr 8;1203:18-25
18313644
Exp Brain Res. 2003 Dec;153(4):655-60
12955379
Hear Res. 2000 Feb;140(1-2):165-72
10675644
Behav Neurosci. 2006 Feb;120(1):188-95
16492129
J Cell Sci. 2007 Mar 1;120(Pt 5):782-91
17284523
Trends Neurosci. 2004 Nov;27(11):676-82
15474168
J Cell Sci. 1998 Feb;111 ( Pt 3):335-45
9427682
Hear Res. 2007 Jun;228(1-2):168-79
17382501
J Comp Neurol. 2005 Oct 3;490(4):391-413
16127711
Curr Pharm Des. 2007;13(23):2350-67
17692006
Brain Res. 1979 Aug 17;172(1):179-85
466463
J Assoc Res Otolaryngol. 2001 Mar;2(1):54-64
11545150
Hear Res. 2005 Jun;204(1-2):90-100
15925194
Hear Res. 2004 Sep;195(1-2):17-34
15350276
Neuron. 1992 Dec;9(6):1155-61
1281418
J Psychosom Res. 1987;31(5):613-21
3430424
Exp Neurol. 1998 Jun;151(2):273-88
9628763
Eur J Neurosci. 1992;4(9):798-812
12106303
Otolaryngol Clin North Am. 1996 Jun;29(3):455-65
8743344
Hear Res. 2005 Aug;206(1-2):200-26
16081009
Neuroscience. 2009 Apr 21;160(1):227-39
19217931
J Cell Sci. 2000 Aug;113 ( Pt 15):2783-95
10893193
Neuron. 2005 Mar 3;45(5):727-39
15748848
Neuroscience. 1999;93(4):1375-81
10501462
J Neurosci Res. 2008 Aug 15;86(11):2564-78
18438941
Acta Otolaryngol. 2000 Sep;120(6):750-6
11099153
Audiology. 1986;25(2):116-23
3707436
Neurosci Res. 1990 Aug;8(4):221-54
2175858
Pediatrics. 2005 Apr;115(4):861-7
15805356
Hear Res. 2000 Sep;147(1-2):282-92
10962192
J Neurosci. 2002 Mar 15;22(6):2383-90
11896177
Trends Neurosci. 2000 Sep;23(9):429-35
10941193
Exp Brain Res. 1989;75(2):381-9
2721616
Physiol Rev. 2004 Oct;84(4):1051-95
15383648
J Cell Biol. 2006 Jan 30;172(3):441-51
16449194
Hear Res. 1998 Mar;117(1-2):81-96
9557979