Retinal ganglion cell projections to the hamster suprachiasmatic nucleus, intergeniculate leaflet, and visual midbrain: Bifurcation and melanopsin immunoreactivity

The circadian clock in the suprachiasmatic nucleus (SCN) receives direct retinal input via the retinohypothalamic tract (RHT), and the retinal ganglion cells contributing to this projection may be specialized with respect to direct regulation of the circadian clock. However, some ganglion cells forming the RHT bifurcate, sending axon collaterals to the intergeniculate leaflet (IGL) through which light has secondary access to the circadian clock. The present studies provide a more extensive examination of ganglion cell bifurcation and evaluate whether ganglion cells projecting to several subcortical visual nuclei contain melanopsin, a putative ganglion cell photopigment. The results showed that retinal ganglion cells projecting to the SCN send collaterals to the IGL, olivary pretectal nucleus, and superior colliculus, among other places. Melanopsin‐immunoreactive (IR) ganglion cells are present in the hamster retina, and some of these cells project to the SCN, IGL, olivary pretectal nucleus, or superior colliculus. Triple‐label analysis showed that melanopsin‐IR cells bifurcate and project bilaterally to each SCN, but not to the other visual nuclei evaluated. The melanopsin‐IR cells have photoreceptive characteristics optimal for circadian rhythm regulation. However, the presence of moderately widespread bifurcation among ganglion cells projecting to the SCN, and projection by melanopsin‐IR cells to locations distinct from the SCN and without known rhythm function, suggest that this ganglion cell type is generalized, rather than specialized, with respect to the conveyance of photic information to the brain. J. Comp. Neurol. 465:401–416, 2003. © 2003 Wiley‐Liss, Inc.

[1]  Jun Lu,et al.  Melanopsin in cells of origin of the retinohypothalamic tract , 2001, Nature Neuroscience.

[2]  A. Joussen,et al.  Latanoprost stimulates secretion of matrix metalloproteinases in tenon fibroblasts both in vitro and in vivo. , 2003, Investigative ophthalmology & visual science.

[3]  D. Berson,et al.  Phototransduction by Retinal Ganglion Cells That Set the Circadian Clock , 2002, Science.

[4]  Raymond D. Lund,et al.  The retinal ganglion cells that drive the pupilloconstrictor response in rats , 1998, Brain Research.

[5]  C. Blakemore,et al.  Functional organization in the visual cortex of the golden hamster , 1976, The Journal of comparative neurology.

[6]  O. E. Millhouse.  Optic chiasm collaterals afferent to the suprachiasmatic nucleus , 1977, Brain Research.

[7]  L. P. Morin,et al.  Interconnections among nuclei of the subcortical visual shell: The intergeniculate leaflet is a major constituent of the hamster subcortical visual system , 1998, The Journal of comparative neurology.

[8]  W. P. Hayes,et al.  A Novel Human Opsin in the Inner Retina , 2000, The Journal of Neuroscience.

[9]  N. Mrosovsky,et al.  Masking of locomotor activity in hamsters , 1999, Journal of Comparative Physiology A.

[10]  U. Dräger,et al.  Origins of uncrossed retinofugal projections in normal and hypopigmented mice , 1990, Visual Neuroscience.

[11]  L. P. Morin.  The circadian visual system , 1994, Brain Research Reviews.

[12]  N. Mrosovsky,et al.  Intergeniculate leaflet lesions and behaviorally-induced shifts of circadian rhythms , 1994, Brain Research.

[13]  R. Lund,et al.  The anatomical substrates subserving the pupillary light reflex in rats: Origin of the consensual pupillary response , 1994, Neuroscience.

[14]  G. Schneider,et al.  Target-specific morphology of retinal axon arbors in the adult hamster , 1998, Visual Neuroscience.

[15]  T. Yamadori,et al.  Bifurcated projections of retinal ganglion cells bilaterally innervate the lateral geniculate nuclei in the cat , 1995, Brain Research.

[16]  L. P. Morin,et al.  Forebrain connections of the hamster intergeniculate leaflet: Comparison with those of ventral lateral geniculate nucleus and retina , 1999, Visual Neuroscience.

[17]  L. P. Morin,et al.  Retinohypothalamic projections in the hamster and rat demonstrated using cholera toxin , 1988, Brain Research.

[18]  G. Schneider,et al.  A minute fraction of Syrian golden hamster retinal ganglion cells project bilaterally , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[19]  C A Wiley,et al.  Tyramide signal amplification method in multiple-label immunofluorescence confocal microscopy. , 1999, Methods.

[20]  R. Foster,et al.  Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors. , 1999, Science.

[21]  Robert J. Lucas,et al.  Characterization of an ocular photopigment capable of driving pupillary constriction in mice , 2001, Nature Neuroscience.

[22]  G. E. Pickard,et al.  The Intergeniculate Leaflet Partially Mediates Effects of Light on Circadian Rhythms , 1987, Journal of biological rhythms.

[23]  A. Cowey,et al.  Bifurcating retinal ganglion cell axons in the rat, demonstrated by retrograde double labelling , 2004, Experimental Brain Research.

[24]  L. P. Morin,et al.  Neuropeptide Y and enkephalin immunoreactivity in retinorecipient nuclei of the hamster pretectum and thalamus , 1997, Visual Neuroscience.

[25]  Barbara L. Finlay,et al.  A neuroethological approach to hamster vision , 1980, Behavioural Brain Research.

[26]  K. Yau,et al.  Melanopsin-Containing Retinal Ganglion Cells: Architecture, Projections, and Intrinsic Photosensitivity , 2002, Science.

[27]  J. Hannibal,et al.  The Photopigment Melanopsin Is Exclusively Present in Pituitary Adenylate Cyclase-Activating Polypeptide-Containing Retinal Ganglion Cells of the Retinohypothalamic Tract , 2002, The Journal of Neuroscience.

[28]  R. F. Johnson,et al.  Lateral geniculate lesions block circadian phase-shift responses to a benzodiazepine. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Bruce F O'Hara,et al.  Role of Melanopsin in Circadian Responses to Light , 2002, Science.

[30]  L. P. Morin,et al.  The Intergeniculate Leaflet, but Not the Visual Midbrain, Mediates Hamster Circadian Rhythm Response to Constant Light , 2002, Journal of biological rhythms.

[31]  C. M. Cicerone,et al.  Cells in the pretectal olivary nucleus are in the pathway for the direct light reflex of the pupil in the rat , 1984, Brain Research.

[32]  R. Moore,et al.  The primary and accessory optic systems in the golden hamster, Mesocricetus auratus. , 1974, Acta anatomica.

[33]  Colin Blakemore,et al.  Regional specialization in the golden hamster's retina , 1976, The Journal of comparative neurology.

[34]  H. Meissl,et al.  Responses of neurones of the rat suprachiasmatic nucleus to retinal illumination under photopic and scotopic conditions , 2000, The Journal of physiology.

[35]  L. P. Morin,et al.  Organization of the hamster intergeniculate leaflet: NPY and ENK projections to the suprachiasmatic nucleus, intergeniculate leaflet and posterior limitans nucleus , 1995, Visual Neuroscience.

[36]  N. Mrosovsky,et al.  Masking by light in hamsters with SCN lesions , 1999, Journal of Comparative Physiology A.

[37]  Paul D. Gamlin,et al.  Functional Architecture of the Photoreceptive Ganglion Cell in Primate Retina: Morphology, Mosaic Organization and Central Targets of Melanopsin Immunostained Cells , 2003 .

[38]  Satchidananda Panda,et al.  Melanopsin (Opn4) Requirement for Normal Light-Induced Circadian Phase Shifting , 2002, Science.

[39]  L. P. Morin,et al.  Intergeniculate leaflet and suprachiasmatic nucleus organization and connections in the golden hamster , 1992, Visual Neuroscience.

[40]  R. Rhoades,et al.  An electronmicroscopic analysis of the optic nerve in the golden hamster , 1979, The Journal of comparative neurology.

[41]  L. P. Morin,et al.  The Hamster Circadian Rhythm System Includes Nuclei of the Subcortical Visual Shell , 1999, The Journal of Neuroscience.

[42]  R. W. Rodieck,et al.  The retinal projection to the cat pretectum , 1985, The Journal of comparative neurology.

[43]  R. Moore,et al.  A retinohypothalamic projection in the rat , 1972, The Journal of comparative neurology.

[44]  B. Rusak,et al.  Photic sensitivity of geniculate neurons that project to the suprachiasmatic nuclei or the contralateral geniculate , 1989, Brain Research.

[45]  R. Moore,et al.  Organization of lateral geniculate‐hypothalamic connections in the rat , 1989, The Journal of comparative neurology.

[46]  R. Moore,et al.  Efferent projections of the intergeniculate leaflet and the ventral lateral geniculate nucleus in the rat , 2000, The Journal of comparative neurology.

[47]  I. W. Mclean,et al.  PERIODATE-LYSINE-PARAFORMALDEHYDE FIXATIVE A NEW FIXATIVE FOR IMMUNOELECTRON MICROSCOPY , 1974, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[48]  L. P. Morin,et al.  Neuromodulator content of hamster intergeniculate leaflet neurons and their projection to the suprachiasmatic nucleus or visual midbrain , 2001, The Journal of comparative neurology.

[49]  G. Schneider,et al.  Topography of visual and somatosensory projections to the superior colliculus of the golden hamster , 1978, Brain Research.

[50]  M. Harrington,et al.  Lesions of the Thalamic Intergeniculate Leaflet Alter Hamster Circadian Rhythms , 1986, Journal of biological rhythms.

[51]  R. Foster,et al.  Identifying the photoreceptive inputs to the mammalian circadian system using transgenic and retinally degenerate mice , 2001, Behavioural Brain Research.

[52]  R. Illing.  Axonal bifurcation of cat retinal ganglion cells as demonstrated by retrograde double labelling with fluorescent dyes , 1980, Neuroscience Letters.

[53]  J. Simpson,et al.  The pretectal nuclear complex and the accessory optic system. , 1988, Reviews of oculomotor research.

[54]  D. Berson,et al.  Are Intrinsically Photosensitive Retinal Ganglion Cells Influenced by Rods or Cones , 2002 .

[55]  R. Foster,et al.  Retinal projections in mice with inherited retinal degeneration: Implications for circadian photoentrainment , 1998, The Journal of comparative neurology.

[56]  R. V. Van Gelder,et al.  Functional redundancy of cryptochromes and classical photoreceptors for nonvisual ocular photoreception in mice. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[57]  G. Aston-Jones,et al.  Evidence that cholera toxin B subunit (CTb) can be avidly taken up and transported by fibers of passage , 1995, Brain Research.

[58]  G. E. Pickard.  Bifurcating axons of retinal ganglion cells terminate in the hypothalamic suppachiasmatic nucleus and the intergeniculate leaflet of the thalamus , 1985, Neuroscience Letters.

[59]  I. Zucker,et al.  Circadian rhythms in drinking behavior and locomotor activity of rats are eliminated by hypothalamic lesions. , 1972, Proceedings of the National Academy of Sciences of the United States of America.

[60]  W. P. Hayes,et al.  Melanopsin: An opsin in melanophores, brain, and eye. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[61]  B. Dreher,et al.  The morphology, number, distribution and central projections of Class I retinal ganglion cells in albino and hooded rats. , 1985, Brain, behavior and evolution.

[62]  N. Mrosovsky,et al.  Enhanced masking response to light in hamsters with IGL lesions , 1999, Journal of Comparative Physiology A.

[63]  F. Turek,et al.  Lesions of the thalamic intergeniculate leafleet block activity-induced phase shifts in the circadian activity rhythm of the golden hamster , 1994, Brain Research.

[64]  K. Yau,et al.  Diminished Pupillary Light Reflex at High Irradiances in Melanopsin-Knockout Mice , 2003, Science.

[65]  B. Rusak.  The role of the suprachiasmatic nuclei in the generation of circadian rhythms in the golden hamster,Mesocricetus auratus , 2004, Journal of comparative physiology.

[66]  P. J. Larsen,et al.  Pituitary Adenylate Cyclase-Activating Peptide (PACAP) in the Retinohypothalamic Tract: A Potential Daytime Regulator of the Biological Clock , 1997, The Journal of Neuroscience.

[67]  B. Stein,et al.  Multimodal Representation in the Superior Colliculus and Optic Tectum , 1984 .

[68]  R. F. Johnson,et al.  Loss of entrainment and anatomical plasticity after lesions of the hamster retinohypothalamic tract , 1988, Brain Research.

[69]  G. E. Pickard.  The afferent connections of the suprachiasmatic nucleus of the golden hamster with emphasis on the retinohypothalamic projection , 1982, The Journal of comparative neurology.