Melanopsin and non-melanopsin expressing retinal ganglion cells innervate the hypothalamic suprachiasmatic nucleus | Visual Neuroscience | Cambridge Core (original) (raw)

Abstract

Retinal input to the hypothalamic suprachiasmatic nucleus (SCN) synchronizes the SCN circadian oscillator to the external day/night cycle. Retinal ganglion cells that innervate the SCN via the retinohypothalamic tract are intrinsically light sensitive and express melanopsin. In this study, we provide data indicating that not all SCN-projecting retinal ganglion cells express melanopsin. To determine the proportion of ganglion cells afferent to the SCN that express melanopsin, ganglion cells were labeled following transsynaptic retrograde transport of a recombinant of the Bartha strain of pseudorabies virus (PRV152) constructed to express the enhanced green fluorescent protein (EGFP). PRV152 injected into the anterior chamber of the eye retrogradely infects four retinorecipient nuclei in the brain via autonomic circuits to the eye, resulting in transneuronally labeled ganglion cells in the contralateral retina 96 h after intraocular infection. In animals with large bilateral lesions of the lateral geniculate body/optic tract, ganglion cells labeled with PRV152 are retrogradely infected from only the SCN. In these animals, most PRV152-infected ganglion cells were immunoreactive for melanopsin. However, a significant percentage (10–20%) of EGFP-labeled ganglion cells did not express melanopsin. These data suggest that in addition to the intrinsically light-sensitive melanopsin-expressing ganglion cells, conventional ganglion cells also innervate the SCN. Thus, it appears that the rod/cone system of photoreceptors may provide signals to the SCN circadian system independent of intrinsically light-sensitive melanopsin ganglion cells.

References

Belenky, M.A.,Smeraski, C.A.,Provencio, I.,Sollars, P.J., &Pickard, G.E.(2003).Melanopsin retinal ganglion cells receive bipolar and amacrine cell synapses.Journal of Comparative Neurology 460,380–393.Google Scholar

Berson, D.M.(2003).Strange vision: Ganglion cells as circadian photoreceptors.Trends in Neuroscience 26,314–320.Google Scholar

Berson, D.M.,Dunn, F.A., &Takao, M.(2002).Phototransduction by retinal ganglion cells that set the circadian clock.Science 295,1070–1073.Google Scholar

Brideau, A.D.,Eldridge, M.G., &Enquist, L.W.(2000).Directional transneuronal infection by pseudorabies virus is dependent on an acidic internalization motif in the Us9 cytoplasmic tail.Journal of Virology 74,4549–4561.Google Scholar

Card, J.P.(1995).Pseudorabies virus replication and assembly in the rodent central nervous system. InViral Vectors. Gene Therapy and Neuroscience Applications, ed.Kaplitt, M.G. &Loewy, A.D., pp.319–345.San Diego, California:Academic Press.

Card, J.P.,Whealy, M.E.,Robbins, A.K.,Moore, R.Y., &Enquist, L.W.(1991).Two alpha-herpevirus strains are transported differentially in the rodent visual system.Neuron 6,957–969.Google Scholar

Chao, T.I.,Grosche, J.,Friedrich, K.J.,Biedermann, B.,Francke, M.,Pannicke, T.,Reichelt, W.,Wulst, M.,Mühle, C.,Pritz-Hohmeier, S.,Kuhrt, H.,Faude, F.,Drommer, W.,Kasper, M.,Buse, E., &Reichenbach, A.(1997).Comparative studies on mammalian Müller (retinal glial) cells.Journal of Neurocytology 26,439–454.Google Scholar

Dunn, F.A. &Berson, D.M.(2002).Are intrinsically photosensitive retinal ganglion cells influenced by rods or cones?[ARVO Abstract]Investigative Ophthalmology and Visual Science 43(4),Abstract nr 2982.Google Scholar

Famiglietti, E.V. &Kolb, H.(1976).Structural basis of “ON”- and “OFF”-center responses in retinal ganglion cells.Science 194,193–195.Google Scholar

Freedman, M.S.,Lucas, R.J.,Soni, B.,von Schantz, M.,Munoz, M.,David-Gray, Z., &Foster, R.(1999).Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors.Science 284,502–504.Google Scholar

Gooley, J.J.,Lu, J.,Chou, T.C.,Scammell, T.E., &Saper, C.B.(2001).Melanopsin in cells of origin of the retinohypothalamic tract.Nature Neuroscience 4,1165.Google Scholar

Gooley, J.J.,Lu, J.,Fischer, D., &Saper, C.B.(2003).A broad role for melanopsin in non-visual photoreception.Journal of Neuroscience,23,7093–7106.Google Scholar

Hannibal, J.,Vrang, N.,Card, J.P., &Fahrenkrug, J.(2001).Light-dependent induction of cFos during subjective day and night in PACAP-containing ganglion cells of the retinohypothalamic tract.Journal of Biological Rhythms 16,457–470.Google Scholar

Hannibal, J.,Hindersson, P.,Knudsen, S.M.,Georg, B., &Fahrenkrug, J.(2002a).The photopigment melanopsin is exclusively present in pituitary adenylate cyclase-activating polypeptide-containing retinal ganglion cells of the retinohypothalamic tract.Journal of Neuroscience 22, RC191(1–7).Google Scholar

Hannibal, J.,Hindersson, P.,Nevo, E., &Fahrehkrug, J.(2002b).The circadian photopigment melanopsin is expressed in the blind subterranean mole rat, Spalax.NeuroReport 13,1411–1414.Google Scholar

Hattar, S.,Liao, H.-W.,Takao, M.,Berson, D.M., &Yau, K.-W.(2002).Melanopsin-containing retinal ganglion cells: Architecture, projections, and intrinsic photosensitivity.Science 295,1065–1070.Google Scholar

Hattar, S.,Lucas, R.J.,Mrosovsky, N.,Thompson, S.,Douglas, R.H.,Hankins, M.W.,Lem, J.,Biel, M.,Hofmann, F.,Foster, R.G., &Yau, K.-W.(2003).Melanopsin and rod–cone photoreceptive systems account for all major accessory visual functions in mice.Nature 424,75–81.Google Scholar

Husak, P.J.,Kuo, T., &Enquist, L.W.(2000).Pseudorabies virus membrane proteins gI and gE facilitate anterograde spread of infection in projection-specific neurons in the rat.Journal of Virology 74,10975–10983.Google Scholar

Johnson, R.F.,Moore, R.Y., &Morin, L.P.(1988).Loss of entrainment and anatomical plasticity after lesions of the hamster retinohypothalamic tract.Brain Research 460,297–313.Google Scholar

Lu, J.,Shiromani, P., &Saper, C.B.(1999).Retinal input to the sleep-active ventrolateral preoptic nucleus in the rat.Neuroscience 93,209–214.Google Scholar

Lucas, R.J.,Freedman, M.S.,Munoz, M.,Garcia-Fernandez, J.M., &Foster, R.G.(1999).Regulation of the mammalian pineal by non-rod, non-cone, ocular photoreceptors.Science 284,505–507.Google Scholar

Moore, R.Y.,Speh, J.C., &Card, J.P.(1995).The retinohypothalamic tract originates from a distinct subset of retinal ganglion cells.Journal of Comparative Neurology 352,351–366.Google Scholar

Morin, L.P. &Blanchard, J.H.(1998).Interconnections among nuclei of the subcortical visual shell: The intergeniculate leaflet is a major constituent of the hamster subcortical visual system.Journal of Comparative Neurology 396,288–309.Google Scholar

Morin, L.P. &Wood, R.I.(2001).A Stereotaxic Atlas of the Golden Hamster Brain.New York:Academic Press.

Morin, L.P.,Goodless-Sanchez, N.,Smale, L., &Moore, R.Y.(1994).Projections of the suprachiasmatic nuclei, subparaventricular zone and retrochiasmatic area in the golden hamster.Neuroscience 61,391–410.Google Scholar

Morin, L.P.,Blanchard, J.H., &Provencio, I.(2003).Retinal ganglion cell projections to the hamster suprachiasmatic nucleus, intergeniculate leaflet, and visual midbrain: Bifurcation and melanopsin immunoreactivity.Journal of Comparative Neurology 465,401–416.Google Scholar

Panda, S.,Sato, T.K.,Castrucci, A.M.,Rollag, M.D.,DeGrip, W.J.,Hogenesch, J.B.,Provencio, I., &Kay, S.A.(2002).Melanopsin (Opn4) requirement for normal light-induced circadian phase shifting.Science 298,2213–2216.Google Scholar

Panda, S.,Provencio, I.,Tu, D.C.,Pires, S.S.,Rollag, M.D.,Castrucci, A.M.,Pletcher, M.T.,Sato, T.K.,Wiltshire, T.,Andahazy, M.,Kay, S.A.,Van Gelder, R.N., &Hogenesch, J.B.(2003).Melanopsin is required for non-image forming photic responses in blind mice.Science 301,525–527.Google Scholar

Pickard, G.E.(1982).The afferent connections of the suprachiasmatic nucleus of the golden hamster with emphasis on the retinohypothalamic projection.Journal of Comparative Neurology 211,65–83.Google Scholar

Pickard, G.E.(1985).Bifurcating axons of retinal ganglion cells terminate in the hypothalamic suprachiasmatic nucleus and the intergeniculate leaflet of the thalamus.Neuroscience Letters 55,211–217.Google Scholar

Pickard, G.E. &Silverman, A.J.(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.Journal of Comparative Neurology 196,155–172.Google Scholar

Pickard, G.E.,Ralph, M., &Menaker, M.(1987).The intergeniculate leaflet partially mediates the effects of light on circadian rhythms.Journal of Biological Rhythms 2,35–56.Google Scholar

Pickard, G.E.,Smeraski, C.A.,Tomlinson, C.C.,Banfield, B.W.,Kaufman, J.,Wilcox, C.L.,Enquist, L.W., &Sollars, P.J.(2002).Intravitreal injection of the attenuated pseudorabies virus, PRV-Bartha, results in infection of the hamster suprachiasmatic nucleus only by retrograde transsynaptic transport via autonomic circuits.Journal of Neuroscience 22,2701–2710.Google Scholar

Provencio, I.,Jiang, G.,DeGrip, W.J.,Hayes, W.P., &Rollag, M.D.(1998).Melanopsin: An opsin in melanophores, brain, and eye.Proceedings of the National Academy of Sciences of the U.S.A. 95,340–345.Google Scholar

Provencio, I.,Rodriguez, I.R.,Jiang, G.,Hayes, W.P.,Moreira, E.F., &Rollag, M.D.(2000).A novel human opsin in the inner retina.Journal of Neuroscience 20,600–605.Google Scholar

Provencio, I.,Rollag, M.D., &Castrucci, A.M.(2002).Photoreceptive net in the mammalian retina.Nature 415,493.Google Scholar

Pu, M.(1999)Dendritic morphology of cat retinal ganglion cells projecting to suprachiasmatic nucleus.Journal of Comparative Neurology 414,267–274.Google Scholar

Ruby, N.F.,Brennan, T.J.,Xie, X.,Cao, V.,Franken, P.,Heller, H.C., &O'Hara, B.F.(2002).Role of melanopsin in circadian responses to light.Science 298,2211–2213.Google Scholar

Sancar, A.(2000).Cryptochrome: The second photoactive pigment in the eye and its role in circadian photoreception.Annual Review of Biochemistry 69,31–67.Google Scholar

Smeraski, C.A.,Sollars, P.J.,Ogilvie, M.D.,Enquist, L.W., &Pickard, G.E.(2004).Suprachiasmatic nucleus input to autonomic circuits identified by retrograde transsynaptic transport of pseudorabies virus from the rat eye.Journal of Comparative Neurology 471,298–313.Google Scholar

Smith, B.N.,Banfield, B.W.,Smeraski, C.A.,Wilcox, C.L.,Dudek, F.E.,Enquist, L.W., &Pickard, G.E.(2000).Pseudorabies virus expressing enhanced green fluorescent protein: A tool for in vitro electrophysiological analysis of transsynaptically labeled neurons in identified CNS circuits.Proceedings of the National Academy of Sciences of the U.S.A. 97,9264–9269.Google Scholar

Strack, A.M. &Loewy, A.D.(1990).Pseudorabies virus: A highly specific transneuronal cell body marker in the sympathetic nervous system.Journal of Neuroscience 10,2139–2147.Google Scholar

Tiao, Y-C. &Blakemore, C.(1976).Regional specialization in the golden hamster's retina.Journal of Comparative Neurology 168,439–458.Google Scholar

Tomishima, M.J. &Enquist, L.W.(2001).A conserved α-herpesvirus protein necessary for axonal localization of viral membrane proteins.Journal of Cell Biology 154,741–752.Google Scholar

Warren, E.J.,Allen, C.N.,Brown, R.L., &Robinson, D.W.(2003).Intrinsic light responses of retinal ganglion cells projecting to the circadian system.European Journal of Neuroscience 17,1727–1735.Google Scholar