title: Encoding visual information in retinal ganglion cells with prosthetic stimulation.
abstract: Retinal prostheses aim to restore functional vision to those blinded by outer retinal diseases using electric stimulation of surviving retinal neurons. The ability to replicate the spatiotemporal pattern of ganglion cell spike trains present under normal viewing conditions is presumably an important factor for restoring high-quality vision. In order to replicate such activity with a retinal prosthesis, it is important to consider both how visual information is encoded in ganglion cell spike trains, and how retinal neurons respond to electric stimulation. The goal of the current review is to bring together these two concepts in order to guide the development of more effective stimulation strategies. We review the experiments to date that have studied how retinal neurons respond to electric stimulation and discuss these findings in the context of known retinal signaling strategies. The results from such in vitro studies reveal the advantages and disadvantages of activating the ganglion cell directly with the electric stimulus (direct activation) as compared to activation of neurons that are presynaptic to the ganglion cell (indirect activation). While direct activation allows high temporal but low spatial resolution, indirect activation yields improved spatial resolution but poor temporal resolution. Finally, we use knowledge gained from in vitro experiments to infer the patterns of elicited activity in ongoing human trials, providing insights into some of the factors limiting the quality of prosthetic vision.
authors: Center for Innovative Visual Rehabilitation, Boston VA Healthcare System, 150 South Huntington Ave, Boston, MA 02130, USA. dfreeman@mit.edu
authors: Daniel K
authors: DK
authors: Freeman
authors: Joseph F
authors: JF
authors: Rizzo
authors: Shelley I
authors: SI
authors: Fried
references: J Neurosci. 2004 Sep 22;24(38):8366-78
references: 15385619
references: Science. 2002 Feb 8;295(5557):1022-5
references: 11834821
references: Ophthalmic Res. 1997;29(5):269-80
references: 9323718
references: J Comp Neurol. 1989 Jun 8;284(2):174-86
references: 2474002
references: Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1486-96
references: 15790920
references: Curr Biol. 2010 Mar 9;20(5):R228-9
references: 20219169
references: Prog Retin Eye Res. 2002 May;21(3):263-302
references: 12052385
references: Neural Comput. 2008 Dec;20(12):2895-936
references: 18533812
references: J Neurophysiol. 2006 Feb;95(2):970-8
references: 16236780
references: Invest Ophthalmol Vis Sci. 2003 Dec;44(12):5362-9
references: 14638739
references: Annu Int Conf IEEE Eng Med Biol Soc. 2010;2010:5919-22
references: 21096939
references: Prog Retin Eye Res. 1998 Oct;17(4):523-63
references: 9777649
references: Physiol Rev. 1991 Apr;71(2):447-80
references: 2006220
references: Arch Ophthalmol. 2009 Apr;127(4):398-401
references: 19365014
references: J Neurosci. 2009 Apr 8;29(14):4675-80
references: 19357292
references: Arch Ophthalmol. 1992 Nov;110(11):1634-9
references: 1444925
references: Arch Ophthalmol. 2004 Apr;122(4):460-9
references: 15078662
references: Prog Brain Res. 2009;175:317-32
references: 19660665
references: Curr Opin Neurobiol. 2003 Aug;13(4):421-7
references: 12965288
references: Prog Brain Res. 2001;134:17-34
references: 11702542
references: J Neurophysiol. 2010 Nov;104(5):2778-91
references: 20810683
references: Science. 1976 Oct 8;194(4261):193-5
references: 959847
references: Nature. 1996 Feb 22;379(6567):728-32
references: 8602219
references: J Neural Eng. 2005 Mar;2(1):S105-20
references: 15876646
references: IEEE Trans Neural Netw. 2004 Sep;15(5):1083-91
references: 15484885
references: Trends Neurosci. 2001 Feb;24(2):113-21
references: 11164942
references: Annu Rev Neurosci. 2008;31:317-38
references: 18558858
references: J Neural Eng. 2007 Mar;4(1):S92-101
references: 17325421
references: Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2606-12
references: 16723477
references: Vision Res. 2003 Nov;43(24):2573-81
references: 13129543
references: IEEE Trans Biomed Eng. 2008 Mar;55(3):1056-62
references: 18334397
references: J Neurophysiol. 2010 Aug;104(2):704-12
references: 20538771
references: Prog Retin Eye Res. 2003 Sep;22(5):607-55
references: 12892644
references: IEEE Trans Biomed Eng. 1986 Oct;33(10):974-7
references: 3770787
references: Science. 1963 Feb 1;139(3553):412-4
references: 13966712
references: J Neurosci. 2001 Dec 15;21(24):9904-16
references: 11739598
references: J Comp Neurol. 1991 Jan 22;303(4):617-36
references: 1707423
references: Invest Ophthalmol Vis Sci. 2010 Feb;51(2):1223-33
references: 19741248
references: Vision Res. 1999 Jul;39(15):2569-76
references: 10396625
references: J Neurophysiol. 1997 May;77(5):2836-41
references: 9163398
references: J Comp Neurol. 2007 Jan 10;500(2):222-38
references: 17111372
references: Neuron. 2010 Jan 28;65(2):150-64
references: 20152123
references: J Neural Eng. 2010 Dec;7(6):066008
references: 21084732
references: J Neurosci Methods. 2009 May 15;179(2):166-72
references: 19428523
references: Vision Res. 2008 Sep;48(20):2070-89
references: 18513781
references: Curr Opin Neurobiol. 2008 Aug;18(4):396-402
references: 18832034
references: Invest Ophthalmol Vis Sci. 2009 Apr;50(4):1483-91
references: 19098313
references: Nat Neurosci. 2003 Jun;6(6):600-8
references: 12740583
references: Curr Biol. 2006 Jul 25;16(14):1428-34
references: 16860742
references: Invest Ophthalmol Vis Sci. 2003 Aug;44(8):3533-43
references: 12882804
references: J Neurosci. 1993 Dec;13(12):5334-55
references: 8254378
references: Eur J Neurosci. 2005 Oct;22(8):2016-26
references: 16262640
references: Neuron. 2002 Dec 5;36(5):909-19
references: 12467594
references: J Neural Eng. 2007 Jun;4(2):1-16
references: 17409475
references: J Neurosci. 2009 Oct 7;29(40):12374-83
references: 19812313
references: Curr Biol. 2004 Sep 7;14(17):1523-30
references: 15341738
references: Nature. 1994 Oct 6;371(6497):511-3
references: 7935763
references: J Neurophysiol. 2006 Aug;96(2):512-21
references: 16835359
references: J Rehabil Res Dev. 1999 Oct;36(4):371-6
references: 10678460
references: Trends Neurosci. 1989 Feb;12(2):75-80
references: 2469215
references: Vision Res. 1983;23(12):1485-93
references: 6666049
references: J Neurophysiol. 2009 Dec;102(6):3260-9
references: 19726725
references: Invest Ophthalmol Vis Sci. 2007 Jul;48(7):3364-71
references: 17591910
references: Invest Ophthalmol Vis Sci. 2008 Jun;49(6):2303-14
references: 18515576
references: J Neurosci. 2008 Apr 23;28(17):4446-56
references: 18434523
references: Nat Neurosci. 2008 Nov;11(11):1343-51
references: 18820692
references: Curr Biol. 2007 Aug 7;17(15):R577-82
references: 17686423
references: J Neurosci. 1998 Mar 15;18(6):2200-11
references: 9482804
references: Neuron. 2003 Jan 9;37(1):15-27
references: 12526769
references: J Neurophysiol. 2004 Aug;92(2):780-9
references: 15277596
references: J Neurophysiol. 2006 Jun;95(6):3311-27
references: 16436479
references: Brain Res. 1975 Nov 21;98(3):417-40
references: 1102064
references: Clin Electroencephalogr. 2001 Jul;32(3):145-51
references: 11512378
references: Vision Res. 2008 Jun;48(14):1562-8
references: 18555890
references: Curr Biol. 1997 Jul 1;7(7):R421-3
references: 9210365
references: Proc R Soc Lond B Biol Sci. 1966 Nov 15;166(1002):80-111
references: 4382694
references: Vision Res. 2000;40(13):1785-95
references: 10814763
references: Network. 1999 Nov;10(4):R1-66
references: 10695759
references: Annu Int Conf IEEE Eng Med Biol Soc. 2009;2009:642-5
references: 19963976
references: J Neurophysiol. 2004 Aug;92(2):1023-33
references: 15071086
references: J Neurophysiol. 2001 Apr;85(4):1351-6
references: 11287459
references: Science. 2002 Mar 29;295(5564):2460-2
references: 11923539
references: J Neurophysiol. 2009 Apr;101(4):1972-87
references: 19193771
references: J Neural Eng. 2007 Mar;4(1):S1-6
references: 17325407
references: Proc Biol Sci. 2011 May 22;278(1711):1489-97
references: 21047851
references: J Neural Eng. 2011 Feb;8(1):016008
references: 21248379
references: J Physiol. 1976 Nov;262(2):265-84
references: 994040
references: Neuron. 2003 Feb 6;37(3):499-511
references: 12575956
references: Int J Neurosci. 2008 Aug;118(8):1131-44
references: 18576211
references: Vision Res. 1999 Jul;39(15):2485-97
references: 10396618
references: J Physiol. 2002 Feb 1;538(Pt 3):787-802
references: 11826165
references: Vis Neurosci. 2008 Jul-Aug;25(4):535-48
references: 18634718
references: J Neurosci. 2006 Aug 9;26(32):8254-66
references: 16899720
references: Network. 2008;19(4):253-85
references: 18991144
references: Vis Neurosci. 2007 Mar-Apr;24(2):217-30
references: 17640413
references: J Neural Eng. 2009 Jun;6(3):035004
references: 19458401
references: Ophthalmology. 2001 Jan;108(1):13-4
references: 11150256
references: Proc Natl Acad Sci U S A. 1997 May 13;94(10):5411-6
references: 9144251
references: IEEE Trans Biomed Eng. 2008 Jun;55(6):1744-53
references: 18714839
references: IEEE Trans Biomed Eng. 1999 May;46(5):505-14
references: 10230129
references: Cell Tissue Res. 2010 Feb;339(2):311-20
references: 19937346
references: Vis Neurosci. 1999 Mar-Apr;16(2):355-68
references: 10367969
references: J Neurosci. 2008 Dec 24;28(52):14282-92
references: 19109509
references: Br J Ophthalmol. 2011 Apr;95(4):539-43
references: 20881025
references: IEEE Trans Neural Syst Rehabil Eng. 2006 Sep;14(3):290-8
references: 17009488
references: J Rehabil Res Dev. 1993;30(1):110-6
references: 8263821
references: Retina. 2002 Aug;22(4):471-7
references: 12172115
references: Annu Int Conf IEEE Eng Med Biol Soc. 2009;2009:4566-8
references: 19963839
references: Invest Ophthalmol Vis Sci. 2010 Dec;51(12):6762-9
references: 20671284
references: Annu Rev Neurosci. 2007;30:1-30
references: 17335403
references: J Neurosci. 2007 Mar 7;27(10):2636-45
references: 17344401
references: Nature. 2003 May 22;423(6938):401-8
references: 12754524
references: J Neural Eng. 2005 Mar;2(1):S16-21
references: 15876650
references: J Biomater Sci Polym Ed. 2007;18(8):1031-55
references: 17705997
references: J Neurosci. 2009 Feb 25;29(8):2467-76
references: 19244521
references: J Physiol. 2009 Jun 15;587(Pt 12):2753-67
references: 19525561
references: J Neurophysiol. 1976 Jul;39(4):852-70
references: 823306
references: J Neural Eng. 2007 Mar;4(1):S7-16
references: 17325418
references: J Neurophysiol. 1997 Oct;78(4):2048-60
references: 9325372
references: Nature. 2007 Oct 4;449(7162):603-6
references: 17851533
references: Korean J Physiol Pharmacol. 2009 Dec;13(6):443-8
references: 20054490
references: Exp Brain Res. 1993;93(3):383-90
references: 8519332
references: Vis Neurosci. 1994 Jan-Feb;11(1):111-8
references: 8011574
references: Annu Int Conf IEEE Eng Med Biol Soc. 2008;2008:1785-8
references: 19163027
references: Science. 1973 Aug 31;181(4102):810-9
references: 4198903
references: Front Neurosci. 2010 Feb 12;4:28
references: 20582268
references: Annu Rev Neurosci. 2000;23:743-75
references: 10845080
references: Science. 1995 Nov 17;270(5239):1207-10
references: 7502047
references: Prog Brain Res. 2005;147:205-18
references: 15581708
references: Invest Ophthalmol Vis Sci. 2003 Nov;44(11):5035-42
references: 14578432
references: Invest Ophthalmol Vis Sci. 2009 Nov;50(11):5017-25
references: 19608533
references: Annu Rev Biomed Eng. 2005;7:361-401
references: 16004575
references: Exp Eye Res. 2006 Aug;83(2):367-73
references: 16616739
references: Proc Natl Acad Sci U S A. 1986 Apr;83(8):2755-7
references: 3458235
references: Nature. 2001 Mar 29;410(6828):583-7
references: 11279496
references: Nature. 1997 Mar 6;386(6620):69-73
references: 9052781
references: Nat Neurosci. 2004 Jan;7(1):13-4
references: 14699413
references: J Neurophysiol. 2009 Nov;102(5):2982-93
references: 19741103
references: Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9666-70
references: 1409680