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melanopsin 332

melanopsin 332






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melanopsin 332 melanopsin 332 Presentation Transcript

  • Melanopsin, Pinopsin and Encephalic Photoreception in Birds Simon Bishop Alice Cowie Emily Purcell Jeannette Shipman Gemma Sykes
  • Outline
    • Photoreception in vertebrates
    • Importance of the pineal gland and melatonin
    • Melanopsin and pinopsin – what are they?
    • How melanopsin and pinopsin entrain melatonin production by the pineal gland to light
  • Photoreception in Vertebrates
    • Most vertebrates (birds included) have both retinal and extra retinal photoreceptors
    • These include:
      • Lateral eyes
      • Deep brain photoreceptors
      • Intracranial pineal organ
      • Intracranial parapineal organ (fish only)
      • Extra-retinal “third eye” (reptiles and amphibians only)
  • Birds and Mammals Compared
  • Mammals and Birds compared
    • Mammals:
      • Eyes are the only photoreceptors .
      • Signals sent from eyes along the retinohypothalamic tract to the SCN, which acts as a MASTER CLOCK.
      • SCN sends inhibitory or stimulatory information to the pineal gland to rhythmically control its production of melatonin.
    • Birds:
      • Much more complex!
      • Eyes , hypothalamus and pineal gland all act as photoreceptors AND circadian oscillators.
      • Melatonin production by the pineal gland can be directly entrained to the environmental light/dark cycle.
  • The Pineal Gland
    • Particularly important in avian photoreception.
    • Small endocrine gland in the brain, developmentally derived from diencephalic tissue.
    • Primary function to rhythmically synthesize and release melatonin .
  • Melatonin
    • Indoleamine hormone.
    • Rhythmically synthesised and released by cells in the pineal gland.
    • Production of melatonin by the pineal gland is stimulated by darkness and inhibited by light.
    • Secretion of melatonin peaks in the middle of the night
    • Output must be entrained to the light dark cycle.
    • Entrainment achieved by photopigments.
  • Phototransduction and Entrainment
    • Experimental evidence suggests two distinct transduction pathways mediate the effects of light on pineal gland melatonin output:
      • One causes the acute suppression of melatonin output
      • One mediates phase shift entrainment of the pineal clock
    • Each pathway is possibly controlled by a different photopigment.
  • What Evidence is there for 2 Phototransduction Pathways?
    • Experiment 1:
      • Deprive cultured pineal cells of Vitamin A
      • Acute effect of light on melatonin production is reduced
      • Phase shifts are unaffected
    • Experiment 2:
      • Apply pertussis toxin to cultured chick pineal cells (interferes with G proteins which are often coupled with photoreceptors)
      • Blocks acute , but not phase-shifting effects of light on melatonin production
  • Pinopsin
    • mRNA rhythmically expressed.
    • Daily rhythm of expression regulated by light and an intrapineal circadian oscillator .
    • Gene expression initially thought to be purely light-controlled.
    • However when chickens/isolated pineal glands were kept in constant darkness rhythmic pinopsin expression continued (albeit at a reduced level).
    • Therefore now know that circadian oscillators must also play a role in its control.
  • Melanopsin
    • Rhythmically expressed (like pinopsin).
    • In constant darkness, daily amplitudes of melanopsin gene expression are not reduced, in some cases seem even to increase.
    • Therefore seems that regulation of melanopsin production is primarily controlled by the pineal circadian oscillator (unlike pinopsin).
  • Daily Cycles in Pinopsin and Melanopsin Levels
    • Pinopsin and melanopsin levels low in early morning (ZT 0 – 6).
    • Increase in middle of day (ZT 6) by approx. 5-fold.
    • Reach a peak between ZT 10 – 12.
    • mRNA levels decrease after lights-off.
    • Return to low nocturnal levels within 4 – 6 hours.
  • Circadian Variations of Melanopsin and Pinopsin mRNA levels in Chick Pineal Glands under LD 12:12 In vivo In vitro Holthues H. et al (2004).
  • Pinopsin – what is it?
    • An opsin-like photopigment .
    • Related to, but distinct from, other visual opsins.
    • First isolated from the pineal gland of the chicken ( Gallus domesticus ).
    • Expressed exclusively in the pineal gland (key difference with melanopsin).
    • Precise role still unclear.
    • Involved in ‘acute suppression’ pathway???
  • Melanopsin – what is it?
    • Opsin-like photopigment, also called Opn4, first isolated from photosensitive skin and retinal cells in the African Claw frog ( Xenopus laevis ).
    • In birds, found in:
      • Specialised photosensitive ganglion cells in the retina
      • Iris muscles
      • Deep brain regions
      • Pineal gland
      • Skin cells
    • Involved in ‘phase-shift entrainment’ pathway???
  • How do they work?
    • Melanopsin
      • Knockout mice have attenuated phase shifting light response
      • Transfection makes non-photosensitive cells respond to light
      • Linked to Gq-type G-proteins and neuron depolarisation
      • But… G-proteins are indiscriminate and use varies between species
    • Pinopsin
      • PTX blocks Gi- and Gt-type G-proteins, blocking the acute effect of light on pinealocytes in vitro.
      • Transducin (Gt1 α ) is coupled with pinopsin in vivo.
      • Pinopsin activated Gt1 in vitro when illuminated
      • Therefore pinopsin-Gt1 pathway contributes to the acute pathway
      • But… Gq/11 α also localises with pinopsin, speculated to be involved with phase-shifting
  • In Summary…
    • Birds have multiple photoreceptors
    • Some involved in vision, others in temporal physiology
    • Pinopsin and melanopsin – two photopigments with a role in controlling daily melatonin output by the pineal gland
    • Exact functions still unknown but:
      • Pinopsin – involved in ‘acute effect’…?
      • Melanopsin – involved in ‘phase-shift entrainment’ effect…?
  • References
    • Natesan A. et al (2002). Rhythm and Soul in the Avian Pineal. Cell Tissue Res 309 35 – 45.
    • Holthues H. et al (2004). Circadian gene expression patterns of melanopsin and pinopsin in the chick pineal gland. Biochem and Biophys Res Comm 326 160 – 165.
    • Oishi T. et al (2001). Multiphotoreceptor and multioscillator system in avian circadian organization Micros Res and Tech 53 43 – 47.
    • Peirson S. and Foster R.G. (2006). Melanopsin: Another Way of Signalling Light. Neuron 49 331-339
    • Okano T. and Fukada Y. (2001). Photoreception and Circadian Clock System of the Chicken Pineal Gland. Micros Res and Tech 53 72-80
    • Wada Y. et al (2000). Phototransduction Molecules in the Pigeon Deep Brain. J. Comp. Neuro . 428 138-144
    • Kumar Nayak S. et al (2007). Role of a Novel Photopigment, Melanopsin, in Behavioural Adaptation to Light. Cell. Mol. Life. Sci 64 144-154
    • Bailey M.J. and Cassone V.M. (2005) Melanopsin Expression in the Chick Retina and Pineal Gland Molecular Brain Research 134 345-398
    • Foster R.G. and Soni B.G. (1998) Extraretinal Photoreceptors and Their Regulation of Temporal Physiology. Reviews of Reproduction 3 145-150
    • Takanaka Y. et al (1998) Light-Dependent Expression of Pinopsin Gene in Chicken Pineal Gland. J. Neurochem . 70 908-913
    • Fu Z. et al. (1998) Vitamin A Deficiency Reduces the Responsiveness of Pineal Gland to Light in Japanese Quail ( Coturnix japonica ) Comp. Biochem. Physiol . 119 593-598