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Intrinsically Photosensitive Retinal Ganglion Cells

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Reviews of Physiology, Biochemistry and Pharmacology

Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 162))

Abstract

Intrinsically photosensitive retinal ganglion cells (ipRGCs) respond to light in the absence of all rod and cone photoreceptor input. The existence of these ganglion cell photoreceptors, although predicted from observations scattered over many decades, was not established until it was shown that a novel photopigment, melanopsin, was expressed in retinal ganglion cells of rodents and primates. Phototransduction in mammalian ipRGCs more closely resembles that of invertebrate than vertebrate photoreceptors and appears to be mediated by transient receptor potential channels. In the retina, ipRGCs provide excitatory drive to dopaminergic amacrine cells and ipRGCs are coupled to GABAergic amacrine cells via gap junctions. Several subtypes of ipRGC have been identified in rodents based on their morphology, physiology and expression of molecular markers. ipRGCs convey irradiance information centrally via the optic nerve to influence several functions including photoentrainment of the biological clock located in the hypothalamus, the pupillary light reflex, sleep and perhaps some aspects of vision. In addition, ipRGCs may also contribute irradiance signals that interface directly with the autonomic nervous system to regulate rhythmic gene activity in major organs of the body. Here we review the early work that provided the motivation for searching for a new mammalian photoreceptor, the ground-breaking discoveries, current progress that continues to reveal the unusual properties of these neuron photoreceptors, and directions for future investigation.

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References

  • Allen AE, Cameron MA, Brown TM et al (2010) Visual responses in mice lacking critical components of all known retinal phototransduction cascades. PLoS ONE 5:e15063

    Google Scholar 

  • Altimus CM, Güler AD, Villa KL et al (2008) Rods-cones and melanopsin detect light and dark to modulate sleep independent of image formation. Proc Natl Acad Sci USA 105:19998–20003

    Article  PubMed  CAS  Google Scholar 

  • Aschoff J (1960) Exogenous and endogenous components in circadian rhythms. Cold Spring Harbor Symp on Quan Biol 25:11–28

    Article  CAS  Google Scholar 

  • Avery DH, Dahl K, Savage MV et al (1997) Circadian temperature and cortisol rhythms during a constant routine are phase-delayed in hypersomnic winter depression. Biol Psychiatry 41:1109–1123

    Article  PubMed  CAS  Google Scholar 

  • Bailes HJ, Lucas RJ (2010) Melanopsin and inner retinal photoreception. Cell Mol Life Sci 67:99–111

    Article  PubMed  CAS  Google Scholar 

  • Balsalobre A, Brown SA, Marcacci L et al (2000) Resetting of circadian time in peripheral tissues by glucocorticoid signaling. Science 289:2344–2347

    Article  PubMed  CAS  Google Scholar 

  • Baver SB, Pickard GE, Sollars PJ et al (2008) Two types of melanopsin retinal ganglion cell differentially innervate the hypothalamic suprachiasmatic nucleus and the olivary pretectal nucleus. Eur J Neurosci 27:1763–1770

    Article  PubMed  Google Scholar 

  • Belenky MA, Smeraski CA, Provencio I et al (2003) Melanopsin retinal ganglion cells receive bipolar and amacrine cell synapses. J Comp Neurol 460:380–393

    Article  PubMed  Google Scholar 

  • Berson DM (2003) Strange vision: ganglion cells as circadian photoreceptors. Trends Neurosci 26:314–320

    Article  PubMed  CAS  Google Scholar 

  • Berson DM (2007) Phototransduction in ganglion-cell photoreceptors. Pflügers Arch 454:849–855

    Article  PubMed  CAS  Google Scholar 

  • Berson DM, Dunn FA, Takao M (2002) Phototransduction by retinal ganglion cells that set the circadian clock. Science 295:1070–1073

    Article  PubMed  CAS  Google Scholar 

  • Berson DM, Castrucci AM, Provencio I (2010) Morphology and mosaics of melanopsin-expressing retinal ganglion cell types in mice. J Comp Neurol 518:2405–2422

    Article  PubMed  Google Scholar 

  • Brainard GC, Hanifin JP, Rollag MD et al (2001) Human melatonin regulation is not mediated by the three cone photopic visual system. J Clin Endocrinol Met 86:433–436

    Article  CAS  Google Scholar 

  • Bramley JR, Wiles EM, Sollars PJ et al (2011) Carbenoxolone blocks the light-evoked rise in intracellular calcium in isolated melanopsin ganglion cell photoreceptors. PLoS ONE 6:e22721

    Article  PubMed  CAS  Google Scholar 

  • Brown TM, Lucas RJ (2009) Melanopsin phototransduction: great excitement over a poor catch. Curr Biol 19:R256–R257

    Article  PubMed  CAS  Google Scholar 

  • Cajal S Ramón y (1894) Les Nouvelles Ideés sur la Structure du Système Nerveux chez l’Homme et chez les Vértebrés. Reinwald, Paris

    Google Scholar 

  • Chambille I (1998) Retinal ganglion cells expressing the FOS protein after light stimulation in the Syrian hamster are relatively insensitive to neonatal treatment with monosodium glutamate. J Comp Neurol 392:458–467

    Article  PubMed  CAS  Google Scholar 

  • Chambille I, Serviere J (1993) Neurotoxic effects of neonatal injections of monosodium L-glutamate (L-MSG) on the retinal ganglion cell layer of the golden hamster: anatomical and functional consequences on the circadian system. J Comp Neurol 338:67–82

    Article  PubMed  CAS  Google Scholar 

  • Chen CK, Burns ME, Spencer M et al (1999) Abnormal photoresponses and light-induced apoptosis in rods lacking rhodopsin kinase. Proc Natl Acad Sci USA 96:3718–3722

    Article  PubMed  CAS  Google Scholar 

  • Chen SK, Badea TC, Hattar S (2011) Photoentrainment and pupillary light reflex are mediated by distinct populations of ipRGCs. Nature 476:92–95

    Article  PubMed  CAS  Google Scholar 

  • Cooper HM, Mure LS (2008) Expected and unexpected properties of melanopsin signaling. J Biol Rhythms 23:392–393

    Article  PubMed  Google Scholar 

  • Cowan WM, Gottlieb DI, Hendrickson AE et al (1972) The autoradiographic demonstration of axonal connection in the central nervous system. Brain Res 37:21–51

    Article  PubMed  CAS  Google Scholar 

  • Dacey DM (1985) Wide-spreading terminal axons in the inner plexiform layer of the cat’s retina: evidence for intrinsic axon collaterals of ganglion cells. J Comp Neurol 242:247–262

    Article  PubMed  CAS  Google Scholar 

  • Dacey DM, Lioa H-W, Peterson BB et al (2005) Melanopsin-expressing ganglion cells in primate retina signal colour and irradiance and project to the LGN. Nature 433:749–754

    Article  PubMed  CAS  Google Scholar 

  • Daniolos A, Lerner AB, Lerner MR (1990) Action of light on frog pigment cells in culture. Pigment Cell Res 3:38–43

    Article  PubMed  CAS  Google Scholar 

  • Darwin C, Darwin F (1880) The power of movements in plants. John Murray, London

    Google Scholar 

  • Davies WIL, Zheng L, Hughes S et al (2011) Functional diversity of melanopsins and their global expression in the teleost retina. Cell Mol Life Sci (in press)

    Google Scholar 

  • De Candolle A (1832) Physiologie vegetale, ou Exposition des forces et des fonctions vitals des vegetaux, Bechet jeune, Paris

    Google Scholar 

  • De Mairan M (1729) Observation botanique. Historie de l’Academie Royale des Sciences, Paris:1

    Google Scholar 

  • DeCoursey PJ (1972) LD ratios and the entrainment of circadian activity in a nocturnal and diurnal rodent. J Comp Physiol 78:221–235

    Article  Google Scholar 

  • de Zavalia N, Plano SA, Fernandez DC et al (2011) Effect of experimental glaucoma on the non-image forming visual system. J Neurochem 117:904–914

    Article  PubMed  CAS  Google Scholar 

  • Do MT, Kang SH, Xue T et al (2009) Photon capture and signaling by melanopsin retinal ganglion cells. Nature 457:281–287

    Article  PubMed  CAS  Google Scholar 

  • Dräger UC, Hubel DH (1978) Studies of visual function and its decay in mice with hereditary retinal degeneration. J Comp Neurol 180:85–114

    Article  PubMed  Google Scholar 

  • Drouyer E, Dkhissi-Benyahya O, Chiquet C et al (2008) Glaucoma alters the circadian timing system. PLoS ONE 3:e3931

    Google Scholar 

  • Dumitrescu ON, Pucci FG, Wong KY et al (2009) Ectopic retinal ON bipolar cell synapses in the OFF inner plexiform layer: contacts with dopaminergic amacrine cells and melanopsin ganglion cells. J Comp Neurol 517:226–244

    Article  PubMed  CAS  Google Scholar 

  • Earnest DJ, Turek FW (1983) Effect of one-second light pulses on testicular function and locomotor activity in the golden hamster. Biol Reprod 28:557–565

    Article  PubMed  CAS  Google Scholar 

  • Ebihara S, Tsuji K (1980) Entrainment of the circadian activity rhythm to the light dark cycle: effective light intensity for a Zeitgeber in the retinal degenerate C3H mouse and normal C57BL mouse. Physiol Behav 24:523–527

    Article  PubMed  CAS  Google Scholar 

  • Ecker J, Dumitrescu ON, Wong KY et al (2010) Melanopsin-expressing retinal ganglion-cell photoreceptors: cellular diversity and role in pattern vision. Neuron 67:49–60

    Article  PubMed  CAS  Google Scholar 

  • Engelund A, Fahrenkrug J, Harrison A et al (2010) Vesicular glutamate transporter 2 (VGLUT2) is co-stored with PACAP in projections from the rat melanopsin-containing retinal ganglion cells. Cell Tiss Res 340:243–255

    Article  CAS  Google Scholar 

  • Famiglietti EV, Kolb H (1976) Structural basis for on- and off-center responses in retinal ganglion cells. Science 194:193–195

    Article  PubMed  Google Scholar 

  • Farber DB, Flannery JG, Bowes-Rickman C (1994) The rd mouse story: Seventy years of research on an animal model of inherited retinal degeneration. Prog Retinal Eye Res 13:31–64

    Article  CAS  Google Scholar 

  • Feigl B, Mattes D, Thomas R et al (2011) Intrinsically photosensitive (melanopsin) retinal ganglion cell function in glaucoma. Invest Ophthalmol Vis Sci 52:4362–4367

    Article  PubMed  CAS  Google Scholar 

  • Foster RG, Provencio I, Hudson D et al (1991) Circadian photoreception in the retinally degenerate mouse (rd/rd). J Comp Physiol A 169:39–50

    Article  PubMed  CAS  Google Scholar 

  • Freedman MS, Lucas RJ, Soni B et al (1999) Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors. Science 284:502–504

    Article  PubMed  CAS  Google Scholar 

  • Fu Y, Liao H-W, Do MTH et al (2005a) Non-image-forming ocular photoreception in vertebrates. Curr Opin Neurobiol 15:415–422

    Article  PubMed  CAS  Google Scholar 

  • Fu Y, Zhong H, Wang M-H H et al (2005b) Intrinsically photosensitive retinal ganglion cells detect light with a vitamin A-based photopigment, melanopsin. Proc Natl Acad Sci USA 102:10339–10344

    Article  PubMed  CAS  Google Scholar 

  • Fyk-Kolodziej B, Dzhagaryan A, Qin P et al (2004) Immunocytochemical localization of three vesicular glutamate transporters in the cat retina. J Comp Neurol 475:518–530

    Article  PubMed  CAS  Google Scholar 

  • Gaus SE, Strecker RE, Tate BA et al (2002) Ventrolateral preoptic nucleus contains sleep-active, galaninergic neurons in multiple mammalian species. Neurosci 115:285–294

    Article  CAS  Google Scholar 

  • Gooley JJ, Lu J, Chou TC et al (2001) Melanopsin in cells of origin of the retinohypothalamic tract. Nat Neurosci 4:1165

    Article  PubMed  CAS  Google Scholar 

  • Gooley JJ, Lu J, Fischer D et al (2003) A broad role for melanopsin in nonvisual photoreception. J Neurosci 23:7093–7106

    PubMed  CAS  Google Scholar 

  • Göz D, Studholme K, Lappi DA et al (2008) Targeted destruction of photosensitive retinal ganglion cells with a saporin conjugate alters the effects of light on mouse circadian rhythms. PLoS ONE 3:e3153

    Article  PubMed  CAS  Google Scholar 

  • Graham DM, Wong KY, Shapiro P et al (2008) Melanopsin ganglion cells use a membrane-associated rhabdomeric phototransduction cascade. J Neurophysiol 99:2522–2532

    Article  PubMed  CAS  Google Scholar 

  • Groos GA, Mason R (1978) Maintained discharge of rat suprachiasmatic neurons at different adaptation levels. Neurosci Lett 8:59–64

    Article  PubMed  CAS  Google Scholar 

  • Groos GA, Mason R (1980) The visual properties of rat and cat suprachiasmatic neurons. J Comp Physiol 135:349–356

    Article  Google Scholar 

  • Güler AD, Ecker JL, Lall GS et al (2008) Melanopsin cells are the principal conduits for rod-cone input to non-image-forming vision. Nature 453:102–105

    Article  CAS  Google Scholar 

  • Hamner KC, Finn JC, Sirohi GS, Hoshizaki T, Carpenter BH (1962) The biological clock at the south pole. Nature 195:476–480

    Article  Google Scholar 

  • Hannibal J, Georg B, Fahrenkrug J (2007) Melanopsin changes in neonatal albino rat independent of rods and cones. NeuroReport 18:81–85

    Article  PubMed  CAS  Google Scholar 

  • Harrington ME, Rusak B (1986) Lesions of the thalamic intergeniculate leaflet alter hamster circadian rhythms. J Biol Rhythms 1:309–325

    Article  PubMed  CAS  Google Scholar 

  • Hartwick ATE, Bramley JR, Yu J et al (2007) Light-evoked calcium responses of isolated melanopsin-expressing retinal ganglion cells. J Neurosci 27:13468–13480

    Article  PubMed  CAS  Google Scholar 

  • Hartwick ATE, Hamilton CM, Baldridge WH (2008) Glutamatergic calcium dynamics and deregulation of rat retinal ganglion cells. J Physiol 586:3425–3446

    Article  PubMed  CAS  Google Scholar 

  • Hatori M, Le H, Vollmers C et al (2008) Inducible ablation of melanopsin-expressing retinal ganglion cells reveals their central role in non-image forming visual responses. PLoS ONE 3:e2451

    Article  PubMed  CAS  Google Scholar 

  • Hattar S, Liao HW, Takao M et al (2002) Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science 295:1065–1070

    Article  PubMed  CAS  Google Scholar 

  • Hattar S, Kumar M, Park A et al (2006) Central projections of melanopsin-expressing retinal ganglion cells in the mouse. J Comp Neurol 497:326–349

    Article  PubMed  Google Scholar 

  • Hendrickson AE, Wagoner N, Cowan WM (1972) An autoradioradiographic and electron microscopic study of retinohypothalamic connections. Z Zellforsch 135:1–26

    Article  PubMed  CAS  Google Scholar 

  • Hoffman T, Schaefer M, Schultz G et al (2002) Subunit composition of mammalian transient receptor potential channels in living cells. Proc Natl Acad Sci USA 99:7461–7466

    Article  CAS  Google Scholar 

  • Horowitz SS, Blanchard J, Morin LP (2004) Intergeniculate leaflet and ventral lateral geniculate nucleus afferent connections: An anatomical substrate for functional input from the vestibulo-visuomotor system. J Comp Neurol 474:227–245

    Article  PubMed  Google Scholar 

  • Hoshi H, Liu W-L, Massey SC et al (2009) ON inputs to the OFF layer: bipolar cells that break the stratification rules of the retina. J Neurosci 29:8875–8883

    Article  PubMed  CAS  Google Scholar 

  • Ishida A, Mutoh T, Ueyama T et al (2005) Light activates the adrenal gland: timing of gene expression and glucocorticoid release. Cell Metab 2:297–307

    Article  PubMed  CAS  Google Scholar 

  • Isoldi MC, Rollag MD, Castrucci AM et al (2005) Rhabdomeric phototransduction initiated by the vertebrate photopigment melanopsin. Proc Natl Acad Sci USA 102:1217–1221

    Article  PubMed  CAS  Google Scholar 

  • Jakobs TC, Ben Y, Masland RH (2007) Expression of mRNA for glutamate receptor subunits distinguishes the major classes of retinal neurons, but is less specific for individual cell types. Mol Vis 13:933–948

    PubMed  CAS  Google Scholar 

  • Jakobs TC, Libby RT, Ben Y et al (2005) Retinal ganglion cell degeneration is topological but not cell type specific in DBA/2J mice. J Cell Biol 171:313–325

    Article  CAS  Google Scholar 

  • Johnson J, Fremeau RT, Duncan JL et al (2007) Vesicular glutamate transporter 1 is required for photoreceptor synaptic signaling but not for intrinsic visual functions. J Neurosci 27:7245–7255

    Article  PubMed  CAS  Google Scholar 

  • Johnson MS (1939) Effect of continuous light on periodic spontaneous activity of white-footed mice (Peromyscus). J Exper Zool 82:315–328

    Article  Google Scholar 

  • Joo HR, Hattar S, Chen SK (2011) Anatomy and targeting of sparsely labeled M1 ipRGC using the inducible Cre/LoxP system. Soc Neurosci 174.04

    Google Scholar 

  • Keeler CE (1924) The inheritance of a retinal abnormality in white mice. Proc Natl Acad Sci USA 10:329–333

    Article  PubMed  CAS  Google Scholar 

  • Keeler CE (1927) Iris movements in blind mice. Am J Physiol 81:107–112

    Google Scholar 

  • Kong J-H, Fish DR, Rockhill RL et al (2005) Diversity of ganglion cells in the mouse retina: unsupervised morphological classification and its limits. J Comp Neurol 489:293–310

    Article  PubMed  Google Scholar 

  • Koyanagi M, Kubokawa K, Tsukamoto H et al (2005) Cephalochordate melanopsin: evolutionary linkage between invertebrate visual cells and vertebrate photosensitive retinal ganglion cells. Curr Biol 15:1065–1069

    Article  PubMed  CAS  Google Scholar 

  • Kumbalasiri T, Rollag MD, Isoldi MC et al (2007) Melanopsin triggers the release of internal calcium stores in response to light. Photochem Photobiol 83:273–279

    Article  PubMed  CAS  Google Scholar 

  • La Morgia C, Ross-Cisneros FN, Sadun AA et al (2010) Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochrondrial optic neuropathies. Brain 133:2426–2438

    Article  PubMed  Google Scholar 

  • Lamont EW, Robinson B, Stewart J et al (2005) The central and basolateral nuclei of the amygdala exhibit opposite diurnal rhythms of expression of the clock protein Period2. Proc Natl Acad Sci USA 102:4180–4184

    Article  PubMed  CAS  Google Scholar 

  • Lazareva OF, Shimizu T, Wasserman EA (2011) How animals see the world. Oxford University Press (in press)

    Google Scholar 

  • Lewy AJ, Sack RL, Miller S et al (1987) Antidepressant and circadian phase-shifting effects of light. Science 235:352–354

    Article  PubMed  CAS  Google Scholar 

  • Li RS, Chen BY, Tay DK et al (2006) Melanopsin-expressing retinal ganglion cells are more injury-resistant in a chronic ocular hypertension model. Invest Ophthalmol Vis Sci 47:2951–2958

    Article  PubMed  Google Scholar 

  • Li SY, Yau SY, Chen BY et al (2008) Enhanced survival of melanopsin-expressing retinal ganglion cells after injury is associated with the PI3 K/Akt pathway. Cell Mol Neurobiol 28:1095–1107

    Article  PubMed  CAS  Google Scholar 

  • Lin B, Koizumi A, Tanaka N et al (2008) Restoration of visual function in retinal degeneration mice by ectopic expression of melanopsin. Proc Natl Acad Sci USA 105:16009–16014

    Article  PubMed  CAS  Google Scholar 

  • Luan L, Ren C, Lau BW-M et al (2011) Y-like retinal ganglion cells innervate the dorsal raphe nucleus in the Mongolian gerbil (Meriones unguiculatus). PLoS ONE 6:e18938

    Article  PubMed  CAS  Google Scholar 

  • Lucas RJ, Freedman MS, Munoz M et al (1999) Regulation of mammalian pineal by non-rod, non-cone, ocular photoreceptors. Science 284:505–507

    Article  PubMed  CAS  Google Scholar 

  • Lucas RJ, Douglas RH, Foster RG (2001) Characterization of an ocular photopigment capable of driving pupillary constriction in mice. Nat Neurosci 4:621–626

    Article  PubMed  CAS  Google Scholar 

  • Lucas RJ, Hattar S, Takao M et al (2003) Diminished papillary light reflex at high irradiances in melanopsin-knockout mice. Science 299:245–247

    Article  PubMed  CAS  Google Scholar 

  • Lupi D, Oster H, Thompson S et al (2008) The acute light-induction of sleep is mediated by OPN-4based photoreception. Nat Neurosci 11:1068–1073

    Article  PubMed  CAS  Google Scholar 

  • Mawad K, Van Gelder RN (2008) Absence of long-wavelength photic potentiation of murine intrinsically photosensitive retinal ganglion cell firing in vitro. J Biol Rhythms 23:387–391

    Article  PubMed  Google Scholar 

  • Meijer JH, Groos GA, Rusak B (1986) Luminance coding in a circadian pacemaker: the suprachiasmatic nucleus of the rat and hamster. Brain Res 382:109–118

    Article  PubMed  CAS  Google Scholar 

  • Melyan Z, Tarttelin EE, Bellingham et al (2005) Addition of human melanopsin renders mammalian cells photoresponsive. Nature 433:741–745

    Article  PubMed  CAS  Google Scholar 

  • Millhouse OE (1977) Optic chiasm collaterals afferent to the suprachiasmatic nucleus. Brain Res 137:351–355

    Article  PubMed  CAS  Google Scholar 

  • Moore RY, Lenn NJ (1972) A retinohypothalamic projection in the rat. J Comp Neurol 146:1–14

    Article  PubMed  CAS  Google Scholar 

  • Morin LP, Blanchard J (1991) Depletion of brain serotonin by 5,7-DHT modifies hamster circadian rhythm response to light. Brain Res 566:173–185

    Article  PubMed  CAS  Google Scholar 

  • Morin LP, Blanchard J (1997) Neuropeptide Y and enkephalin immunoreactivity in retinorecipient nuclei of the hamster pretectum and thalamus. Vis Neurosci 14:765–777

    Article  PubMed  CAS  Google Scholar 

  • Morin LP, Blanchard J (1998) Interconnections among nuclei of the subcortical visual shell: the intergeniculate leaflet is a major constituent of the hamster subcortical visual system. J Comp Neurol 396:288–309

    Article  PubMed  CAS  Google Scholar 

  • Morin LP, Studholme KM (2011) Separation of function for classical and ganglion cell photoreceptors with respect to circadian rhythm entrainment and induction of photosomnolence. Neurosci (in press)

    Google Scholar 

  • Morin LP, Blanchard J, Moore RY (1992) Intergeniculate leaflet and suprachiasmatic nucleus organization and connections in the golden hamster. Vis Neurosci 8:219–230

    Article  PubMed  CAS  Google Scholar 

  • Morin LP, Blanchard JH, Provencio I (2003) Retinal ganglion cell projections to the hamster suprachiasmatic nucleus, intergeniculate leaflet, and visual midbrain: bifurcation and melanopsin immunoreactivity. J Comp Neurol 465:401–416

    Article  PubMed  Google Scholar 

  • Morin LP, Lituma PJ, Studholme KM (2010) Two components of nocturnal locomotor suppression by light. J Biol Rhythms 25:197–207

    Article  PubMed  Google Scholar 

  • Müller LPS, Do MTH, Yau KW et al (2010) Tracer coupling of intrinsically photosensitive retinal ganglion cells to amacrine cells in the mouse retina. J Comp Neurol 518:4813–4824

    Article  PubMed  Google Scholar 

  • Mure LS, Rieux C, Hattar S et al (2007) Melanopsin-dependent nonvisual responses: evidence for photopigment bistability in vivo. J Biol Rhythms 22:411–424

    Article  PubMed  Google Scholar 

  • Mure LS, Cornut P-L, Rieux C et al (2009) Melanopsin bistability: a fly’s eye technology in the human retina. PLoS ONE 4:e5991

    Article  PubMed  CAS  Google Scholar 

  • Nelson DE, Takahashi JS (1999) Integration and saturation within the circadian photic entrainment pathway of hamsters. Am J Physiol 46:R1351–R1361

    Google Scholar 

  • Nelson RJ, Zucker I (1981) Absence of extraocular photoreception in diurnal and nocturnal rodents exposed to direct sunlight. J Comp Biochem Physiol 69A:145–148

    Article  Google Scholar 

  • Nelson R, Famiglietti EV, Kolb H (1978) Intracellular staining reveals different levels of stratification for on- and off-center ganglion cells in cat retina. J Neurophysiol 41:472–483

    PubMed  CAS  Google Scholar 

  • Nemeroff CB, Konkol RJ, Bissette G et al (1977) Analysis of the disruption in hypothalamic-pituitary regulation in rats treated neonatally with monosodium L-glutamate (MSG): evidence for involvement of tuberoinfundibular cholinergic and dopaminergic systems in neuroendocrine regulation. Endocrinol 101:613–622

    Article  CAS  Google Scholar 

  • Newman LA, Walker MT, Brown RL et al (2003) Melanopsin forms a functional short-wavelength photopigment. Biochem 42:12734–12738

    Article  CAS  Google Scholar 

  • Nickle B, Robinson PR (2007) The opsins of the vertebrate retina: insights from structural, biochemical, and evolutionary studies. Cell Mol Life Sci 64:2917–2932

    Article  PubMed  CAS  Google Scholar 

  • Olney JW (1969) Glutamate induced retinal degeneration in neonatal mice. Electron microscopy of the acutely evolving lesion. J Neuropathol Exp Neurol 28:455–474

    Article  PubMed  CAS  Google Scholar 

  • Oster H, Damerow S, Kiessling S et al (2006) The circadian rhythm of glucocorticoids is regulated by a gating mechanism residing in the adrenal cortical clock. Cell Metab 4:163–173

    Article  PubMed  CAS  Google Scholar 

  • Ostergaard J, Hannibal J, Fahrenkrug J (2007) Synaptic contact between melanopsin-containing retinal ganglion cells and rod bipolar cells. Invest Ophthalmol Vis Sci 48:3812–3820

    Article  PubMed  Google Scholar 

  • Panda S, Sato TK, Castrucci AM et al (2002) Melanopsin (Opn4) requirement for normal light-induced circadian phase shifting. Science 298:2213–2216

    Article  PubMed  CAS  Google Scholar 

  • Panda S, Provencio I, Tu DC et al (2003) Melanopsin is required for non-image-forming photic responses in blind mice. Science 301:525–527

    Article  PubMed  CAS  Google Scholar 

  • Panda S, Nayak SK, Campo B et al (2005) Illumination of the melanopsin signaling pathway. Science 307:600–604

    Article  PubMed  CAS  Google Scholar 

  • Peirson SN, Oster H, Jones SL et al (2007) Microarry analysis and functional genomics identify novel components of melanopsin signaling. Curr Biol 17:1363–1372

    Article  PubMed  CAS  Google Scholar 

  • Peirson SN, Halford S, Foster RG (2009) The evolution of irradiance detection: melanopsin and the non-visual opsins. Phil Trans R Soc B 364:2849–2865

    Article  PubMed  CAS  Google Scholar 

  • Perez-Leighton CE, Schmidt TM, Abramowitz J et al (2011) Intrinsic phototransduction persists in melanopsin-expressing ganglion cells lacking diacylglycerol-sensitive TRPC subunits. Eur J Neurosci 33:856–867

    Article  PubMed  Google Scholar 

  • Perez-Leon JA, Warren EJ, Allen CN et al (2006) Synaptic inputs to retinal ganglion cells that set the circadian clock. Eur J Neurosci 24:1117–1123

    Article  PubMed  Google Scholar 

  • Peterson BB, Dacey DM (1998) Morphology of human retinal ganglion cells with intraretinal axon collaterals. Vis Neurosci 15:377–387

    Article  PubMed  CAS  Google Scholar 

  • Pickard GE (1980) Morphological characteristics of retinal ganglion cells projecting to the suprachiasmatic nucleus: a horseradish peroxidase study. Brain Res 183:458–465

    Article  PubMed  CAS  Google Scholar 

  • Pickard GE (1982) The afferent connections of the suprachiasmatic nucleus of the golden hamster with emphasis on the retinohypothalamic projection. J Comp Neurol 211:65–83

    Article  PubMed  CAS  Google Scholar 

  • Pickard GE (1985) Bifurcating axons of retinal ganglion cells terminate in the hypothalamic suprachiasmatic nucleus and the intergeniculate leaflet of the thalamus. Neurosci Lett 55:211–217

    Article  PubMed  CAS  Google Scholar 

  • Pickard GE (1989) Entrainment of the circadian rhythm of wheel running activity is phase shifted by ablation of the intergeniculate leaflet. Brain Res 494:151–154

    Article  PubMed  CAS  Google Scholar 

  • Pickard GE, Silverman AJ (1981) Direct retinal projections to the hypothalamus, piriform cortex and accessory optic nuclei in the golden hamster as demonstrated by a sensitive anterograde horseradish peroxidase technique. J Comp Neurol 196:155–172

    Article  PubMed  CAS  Google Scholar 

  • Pickard GE, Turek FW, Lamperti AA et al (1982) The effect of neonatally administered monosodium glutamate (MSG) on the development of retinofugal projections and entrainment of circadian locomotor activity. Behav Neural Biol 34:433–444

    Article  PubMed  CAS  Google Scholar 

  • Pickard GE, Ralph M, Menaker M (1987) The intergeniculate leaflet partially mediates the effects of light on circadian rhythms. J Biol Rhythms 2:35–56

    Article  PubMed  CAS  Google Scholar 

  • Pickard GE, Weber TE, Scott PA et al (1996) 5HT1B receptor agonists inhibit light-induced phase shifts of the circadian activity rhythm and expression of the immediate-early gene c-fos in the suprachiasmatic nucleus. J Neurosci 16:8208–8220

    PubMed  CAS  Google Scholar 

  • Pickard GE, Smith BN, Belenky M et al (1999) 5HT1B receptor-mediated presynaptic inhibition of retinal input to the suprachiasmatic nucleus. J Neurosci 19:4034–4045

    PubMed  CAS  Google Scholar 

  • Pickard GE, Baver SB, Ogilvie MD et al (2009) Light-induced Fos expression in intrinsically photosensitive retinal ganglion cells in melanopsin knockout (Opn4−/−) mice. PLoS ONE 4:e4984

    Article  PubMed  CAS  Google Scholar 

  • Pires SS, Hughes S, Turton M et al (2009) Differential expression of two distinct functional isoforms of melanopsin (Opn4) in the mammalian retina. J Neurosci 29:12332–12342

    Article  PubMed  CAS  Google Scholar 

  • Pittendrigh CS (1954) On temperature independence in the clock-system controlling emergence time in Drosophlia. Proc Natl Acad Sci USA 40:1018–1029

    Article  PubMed  CAS  Google Scholar 

  • Provencio I, Jiang G, de Grip WJ et al (1998) Melanopsin: an opsin in melanophores, brain and eye. Proc Natl Acad Sci USA 95:340–345

    Article  PubMed  CAS  Google Scholar 

  • Provencio I, Rodriguez IR, Jiang G et al (2000) A novel human opsin in the inner retina. J Neurosci 20:600–605

    PubMed  CAS  Google Scholar 

  • Provencio I, Rollag MD, Castrucci AM (2002) Photoreceptive net in the mammalian retina. Nature 415:493

    Article  PubMed  CAS  Google Scholar 

  • Qiu X, Kumbalasiri T, Carlson SM et al (2005) Induction of photosensitivity by heterologous expression of melanopsin. Nature 433:745–749

    Article  CAS  Google Scholar 

  • Rajaraman K (2012) ON ganglion cells are intrinsically photosensitive in the tiger salamander retina. J Comp Neurol 520:100–200

    Google Scholar 

  • Richter CP (1965) Biological clocks in medicine and psychiatry. Charles C Thomas, Springfield

    Google Scholar 

  • Robinson GA, Madison RD (2004) Axotomized mouse retinal ganglion cells containing melanopsin show enhanced survival, but not enhanced axon regrowth into a peripheral nerve graft. Vis Res 44:2667–2674

    Article  PubMed  CAS  Google Scholar 

  • Rockhill RL, Daly FJ, MacNeil MA et al (2002) The diversity of ganglion cells in a mammalian retina. J Neurosci 22:3831–3843

    PubMed  CAS  Google Scholar 

  • Roecklein KA, Rohan KJ, Duncan WC et al (2009) A missense variant (P10L) of the melanopsin (OPN4) gene in seasonal affective disorder. J Affect Disorders 114:279–285

    Article  PubMed  CAS  Google Scholar 

  • Ruby NF, Brennan TJ, Xie X et al (2002) Role of melanopsin in circadian responses to light. Science 298:2211–2213

    Article  PubMed  CAS  Google Scholar 

  • Schmidt TM, Kofuji P (2009) Functional and morphological differences among intrinsically photosensitive retinal ganglion cells. J Neurosci 29:476–482

    Article  PubMed  CAS  Google Scholar 

  • Schmidt TM, Kofuji P (2010) Differential cone pathway influence on intrinsically photosensitive retinal ganglion cells subtypes. J Neurosci 30:16262–16271

    Article  PubMed  CAS  Google Scholar 

  • Schmidt TM, Kofuji P (2011) Structure and function of bistratified intrinsically photosensitive retinal ganglion cells in the mouse. J Comp Neurol 519:1492–1504

    Article  PubMed  CAS  Google Scholar 

  • Schmidt TM, Taniguchi K, Kofuji P (2008) Intrinsic and extrinsic light responses in melanopsin-expressing cells during development. J Neurophysiol 100:371–384

    Article  PubMed  CAS  Google Scholar 

  • Schmidt TM, Chen SK, Hattar S (2011) Intrinsically photosensitive retinal ganglion cells: many subtypes, diverse functions. Trends Neurosci 34:572–580

    Google Scholar 

  • Sekaran S, Foster RG, Lucas RJ et al (2003) Calcium imaging reveals a network of intrinsically light-sensitive inner-retinal neurons. Curr Biol 13:1290–1298

    Article  PubMed  CAS  Google Scholar 

  • Sekaran S, Lupi D, Jones CJ et al (2005) Melanopsin-dependent photoreception provides earliest light detection in the mammalian retina. Curr Biol 15:1099–1107

    Article  PubMed  CAS  Google Scholar 

  • Sekaran S, Lall GS, Ralphs KL et al (2007) 2-aminoethoxydiphenylborane is an acute inhibitor of directly photosensitive retinal ganglion cell activity in vitro and in vivo. J Neurosci 27:3981–3986

    Article  PubMed  CAS  Google Scholar 

  • Smale L, Michels KM, Moore RY et al (1990) Destruction of the hamster serotonergic system by 5,7-DHT: effects on circadian rhythm phase, entrainment and response to triazolam. Brain Res 515:9–19

    Article  PubMed  CAS  Google Scholar 

  • Sollars PJ, Smeraski CA, Kaufman JD et al (2003) Melanopsin and non-melanopsin expressing retinal ganglion cells innervate the hypothalamic suprachiasmatic nucleus. Vis Neurosci 20:601–610

    Article  PubMed  Google Scholar 

  • Sollars PJ, Ogilvie MD, Simpson AM et al (2006) Photic entrainment is altered in the 5-HT1B receptor knockout mouse. J Biol Rhythms 21:21–32

    Article  PubMed  CAS  Google Scholar 

  • Son GH, Chung S, Hk C et al (2008) Adrenal peripheral clock controls the autonomous circadian rhythm of glucocorticoid by causing rhythmic steroid production. Proc Natl Acad Sci USA 105:20970–20975

    Article  PubMed  CAS  Google Scholar 

  • Stephan FK, Zucker I (1972) Circadian rhythms in drinking behavior and locomotor activity of rats are eliminated by hypothalamic lesions. Proc Natl Acad Sci USA 69:1583–1586

    Article  PubMed  CAS  Google Scholar 

  • Swanson LW, Cowan WM, Jones EG (1974) An autoradioradiographic study of the efferent connections of the ventral lateral geniculate nucleus in the albino rat and cat. J Comp Neurol 156:143–163

    Article  PubMed  CAS  Google Scholar 

  • Takahashi JS, DeCoursey PJ, Bauman L et al (1984) Spectral sensitivity of a novel photoreceptive system mediating entrainment of mammalian circadian rhytms. Nature 308:186–188

    Article  Google Scholar 

  • Terman M, Terman JS (2005) Light therapy. In: Kryger MH, Roth T, Dement WC (eds) Principles and practice of sleep medicine, 4th edn. Elsevier, Philadelphia, pp 1424–1442

    Chapter  Google Scholar 

  • Thapan K, Arendt J, Skene DJ (2001) An action spectrum for melatonin suppression: evidence for a novel non-rod, non-cone photoreceptor system in humans. J Physiol 535:261–267

    Article  PubMed  CAS  Google Scholar 

  • Torii M, Kojima D, Okano T et al (2007) Two isoforms of chicken melanopsins show blue light sensitivity. FEBS Lett 581:5327–5331

    Article  PubMed  CAS  Google Scholar 

  • Tsai JW, Hannibal J, Hagiwara G et al (2009) Melanopsin as a sleep modulator: circadian gating of direct effects of light on sleep and altered sleep homeostasis in Opn4 −/− mice. PLoS Biol 7:e1000125

    Article  PubMed  CAS  Google Scholar 

  • Usai C, Ratto GM, Bisti S (1991) Two systems of branching axons in monkey’s retina. J Comp Neurol 308:149–161

    Article  PubMed  CAS  Google Scholar 

  • Van den Pol AN, Cao V, Heller HC (1998) Circadian system of mice integrates brief light stimuli. Am J Physiol 275:R654–R657

    Google Scholar 

  • Van Gelder RN (2008) Non-visual photoreception: sensing light without sight. Curr Biol 18:R38–R39

    Article  PubMed  CAS  Google Scholar 

  • Van Gelder RN, Mawad K (2008) Illuminating the mysteries of melanopsin and circadian photoreception. J Biol Rhythms 23:394–395

    Article  Google Scholar 

  • Vessey JP, Lalonde MR, Mizan HA (2004) Carbenoxolone inhibition of voltage-gated Ca channels and synaptic transmission in the retina. J Neurophysiol 92:1252–1256

    Article  PubMed  CAS  Google Scholar 

  • Vidal L, Morin LP (2007) Absence of normal photic integration in the circadian visual system: response to millisecond light flashes. J Neurosci 27:3375–3382

    Article  PubMed  CAS  Google Scholar 

  • Viney TJ, Balint K, Hillier D et al (2007) Local retinal circuits of melanopsin-containing ganglion cells identified by transsynaptic viral tracing. Curr Biol 17:981–988

    Article  PubMed  CAS  Google Scholar 

  • Vugler AA, Redgrave P, Semo M et al (2007) Dopamine neurons form a discrete plexus with melanopsin cells in normal and degenerating retina. Exp Neurol 205:26–35

    Article  PubMed  CAS  Google Scholar 

  • Walker MT, Brown RL, Cronin TW et al (2008) Photochemistry of retinal chromophore in mouse melanopsin. Proc Natl Acad Sci USA 105:8861–8865

    Article  PubMed  CAS  Google Scholar 

  • Wang JS, Kefalov VJ (2009) An alternative pathway mediates the mouse and human cone visual cycle. Curr Biol 19:1665–1669

    Article  PubMed  CAS  Google Scholar 

  • Wang HZ, Lu QJ, Wang NL (2008) Loss of melanopsin-containing retinal ganglion cells in a rat glaucoma model. Chin Med J 121:1015–1019

    PubMed  Google Scholar 

  • Wang JS, Estevez ME, Cornwall MC et al (2009) Intra-retinal visual cycle required for rapid and complete cone dark adaptation. Nat Neurosci 12:295–302

    Article  PubMed  CAS  Google Scholar 

  • Wang X, Wang T, Jiao Y et al (2010) Requirement for an enzymatic visual cycle in Drosophlia. Curr Biol 20:93–102

    Article  PubMed  CAS  Google Scholar 

  • Warren EJ, Allen CN, Brown RL et al (2003) Intrinsic light responses of retinal ganglion cells projecting to the circadian system. Eur J Neurosci 17:1727–1735

    Article  PubMed  Google Scholar 

  • Warren EJ, Allen CN, Brown RL et al (2006) The light-activated signaling pathway in SCN-projecting rat retinal ganglion cells. Eur J Neurosci 23:2477–2487

    Article  PubMed  Google Scholar 

  • Wässle H (2004) Parallel processing in the mammalian retina. Nat Rev Neurosci 5:747–757

    Article  PubMed  CAS  Google Scholar 

  • Wiles EM, Sollars PJ, Pickard GE (2011) Intrinsically photosensitive retinal ganglion cells isolated from neonatal rat retina are depolarized by glycine. Soc Neurosci 602.14

    Google Scholar 

  • Witkovsky P (2004) Dopamine and retinal function. Doc Ophthalmol 108:17–40

    Article  PubMed  Google Scholar 

  • Wong KY, Dunn FA, Berson DM (2005) Photoreceptor adaptation in intrinsically photosensitive retinal ganglion cells. Neuron 48:1001–1010

    Article  PubMed  CAS  Google Scholar 

  • Wong KY, Dunn FA, Graham DM et al (2007) Synapic influences on rat ganglion-cell photoreceptors. J Physiol 582:279–296

    Article  PubMed  CAS  Google Scholar 

  • Yau K-W, Hardie RC (2009) Phototransduction motifs and variations. Cell 139:247–264

    Article  CAS  Google Scholar 

  • Ye H, Baba MD, Peng RW et al (2011) A synthetic optogenetic transcription device enhances blood-glucose homeostasis in mice. Science 332:1565–1568

    Article  PubMed  CAS  Google Scholar 

  • Yoshimura T, Ebihara S (1996) Spectral sensitivity of photoreceptors mediating phase-shifts of circadian rhythms in retinally degenerate CBA/J (rd/rd) and normal CBA/N (+/+) mice. J Comp Physiol 178:797–802

    Article  CAS  Google Scholar 

  • Zaida F, Hull JT, Peirson SN et al (2007) Short-wavelenfth light sensitivity of circadian, pupillary, and visual awareness in humans lacking an outer retina. Curr Biol 17:2122–2128

    Article  CAS  Google Scholar 

  • Zhang DQ, Zhou TR, McMahon DG (2007) Functional heterogeneity of retinal dopaminergic neurons underlying their multiple roles in vision. J Neurosci 27:692–699

    Article  PubMed  CAS  Google Scholar 

  • Zhang DQ, Wong KY, Sollars PJ et al (2008) Intraretinal signaling by ganglion cell photoreceptors do dopaminergic amacrine neurons. Proc Natl Acad Sci USA 105:14181–14186

    Article  PubMed  CAS  Google Scholar 

  • Zhang DQ, Sollars PJ, Pickard GE (2010) Signaling by ganglion cell photoreceptors to dopaminergic amacrine cells requires the photopigment melanopsin and AMP-type glutamate receptors. ARVO #1206

    Google Scholar 

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Acknowledgment

Supported by grants from the National Institutes of Health; National Institute of Neurological Disorders and Stroke R01 NS035615 and National Eye Institute R01 EY017809.

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Authors and Affiliations

  1. School of Veterinary Medicine and Biomedical Sciences, University of Nebraska, Lincoln, NE, 68583, USA

    Gary E. Pickard & Patricia J. Sollars

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  1. Gary E. Pickard
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  2. Patricia J. Sollars
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Correspondence to Gary E. Pickard .

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Editors and Affiliations

  1. Lab. Fysiologie, Katholieke Universiteit Leuven, Herestraat 49, Leuven, 3000, Belgium

    Bernd Nilius

  2. School of Medicine, Deptartment of Neurobiology, University of Pittsburgh, Fifth Avenue 3501, Pittsburgh, 15261, Pennsylvania, USA

    Susan G. Amara

  3. Medizinische Fakultät, Walther-Straub-Institut für Pharmakologi, Ludwig-Maximilians-Universität München, Goethestr. 33, München, 80336, Germany

    Thomas Gudermann

  4. Abt. Neurobiologie, MPI für Biophysikalische Chemie, Am Faßberg 11, Göttingen, 37077, Germany

    Reinhard Jahn

  5. Inst. Zytobiologie und, Zytopathologie, Universität Marburg, Robert-Koch-Str. 5, Marburg, 35033, Germany

    Roland Lill

  6. , Abteilung II, Max-Planck-Institut für Herz- und Lungen, Ludwigstr. 43, Bad Nauheim, 61231, Germany

    Stefan Offermanns

  7. School of Biosciences, Cardiff University, Museum Ave., Cardiff, CF10 3US, United Kingdom

    Ole H. Petersen

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Pickard, G.E., Sollars, P.J. (2011). Intrinsically Photosensitive Retinal Ganglion Cells. In: Nilius, B., et al. Reviews of Physiology, Biochemistry and Pharmacology. Reviews of Physiology, Biochemistry and Pharmacology, vol 162. Springer, Berlin, Heidelberg. https://doi.org/10.1007/112_2011_4

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