Skip to main content
SpringerLink
Log in

Functional Assessment of Melanopsin-Driven Light Responses in the Mouse: Multielectrode Array Recordings

  • Protocol
  • First Online:
Mouse Retinal Phenotyping

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1753))

Abstract

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are a special subset of retinal output neurons capable of detecting and responding to light via a unique photopigment called melanopsin. Melanopsin activation is essential to a wide array of physiological functions, especially to those related to non-image-forming vision. Since ipRGCs only constitute a very small proportion of retinal ganglion cells, targeted recording of melanopsin-driven responses used to be a big challenge to vision researchers. Multielectrode array (MEA) recording provides a noninvasive, high throughput method to monitor melanopsin-driven responses. When synaptic inputs from rod/cone photoreceptors are silenced with glutamatergic blockers, extracellular electric signals derived from melanopsin activation can be recorded from multiple ipRGCs simultaneously by tens of microelectrodes aligned in an array. In this chapter we describe how our labs have approached MEA recording of melanopsin-driven light responses in adult mouse retinas. Instruments, tools and chemical reagents routinely used for setting up a successful MEA recording are listed, and a standard experimental procedure is provided. The implementation of this technique offers a useful paradigm that can be used to conduct functional assessments of ipRGCs and NIF vision.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. 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  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  7. Hattar S, Lucas RJ, Mrosovsky N et al (2003) Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice. Nature 424:76–81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. 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  CAS  PubMed  Google Scholar 

  9. Barnard AR, Hattar S, Hankins MW et al (2006) Melanopsin regulates visual processing in the mouse retina. Curr Biol 16:389–395

    Article  CAS  PubMed  Google Scholar 

  10. Lupi D, Oster H, Thompson S et al (2008) The acute light-induction of sleep is mediated by OPN4-based photoreception. Nat Neurosci 11:1068–1073

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  12. Renna JM, Weng S, Berson DM (2011) Light acts through melanopsin to alter retinal waves and segregation of retinogeniculate afferents. Nat Neurosci 14:827–829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  14. Ecker JL, 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  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Tu DC, Zhang D, Demas J et al (2005) Physiologic diversity and development of intrinsically photosensitive retinal ganglion cells. Neuron 48:987–999

    Article  CAS  PubMed  Google Scholar 

  18. Weng S, Wong KY, Berson DM (2009) Circadian modulation of melanopsin-driven light response in rat ganglion-cell photoreceptors. J Biol Rhythm 24:391–402

    Article  CAS  Google Scholar 

  19. Weng S, Estevez ME, Berson DM (2013) Mouse ganglion-cell photoreceptors are driven by the most sensitive rod pathway and by both types of cones. PLoS One 8:e66480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Margolis DJ, Detwiler PB (2007) Different mechanisms generate maintained activity in ON and OFF retinal ganglion cells. J Neurosci 27:5994–6005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lax P, Esquiva G, Fuentes-Broto L et al (2016) Age-related changes in photosensitive melanopsin-expressing retinal ganglion cells correlate with circadian rhythm impairments in sighted and blind rats. Chronobiol Int 33:374–391

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Sexton TJ, Bleckert A, Turner MH et al (2015) Type I intrinsically photosensitive retinal ganglion cells of early post-natal development correspond to the M4 subtype. Neural Dev 10:17

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  25. Sakamoto K, Liu C, Tosini G (2004) Classical photoreceptors regulate melanopsin mRNA levels in the rat retina. J Neurosci 24:9693–9697

    Article  CAS  PubMed  Google Scholar 

  26. Estevez ME, Fogerson PM, Ilardi MC et al (2012) Form and function of the M4 cell, an intrinsically photosensitive retinal ganglion cell type contributing to geniculocortical vision. J Neurosci 32:13608–13620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Schmidt TM, Alam NM, Chen S et al (2014) A role for melanopsin in alpha retinal ganglion cells and contrast detection. Neuron 82:781–788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Zhao X, Stafford BK, Godin AL et al (2014) Photoresponse diversity among the five types of intrinsically photosensitive retinal ganglion cells. J Physiol 592:1619–1636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Henze DA, Borhegyi Z, Csicsvari J et al (2000) Intracellular features predicted by extracellular recordings in the hippocampus in vivo. J Neurophysiol 84:390–400

    Article  CAS  PubMed  Google Scholar 

  30. Marre O, Amodei D, Deshmukh N et al (2012) Mapping a complete neural population in the retina. J Neurosci 32:14859–14873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Segev R, Goodhouse J, Puchalla J et al (2004) Recording spikes from a large fraction of the ganglion cells in a retinal patch. Nat Neurosci 7:1154–1161

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The research of the authors is supported by grants from the National Natural Science Foundation of China (31571072, 31100796, 31571075, 31171005, 31421091, 81790640 and 81430007); the Ministry of Science and Technology of China (2011CB504602 and 2015AA020512); NIH R15 EY026255 and the Karl Kirchgessner Foundation.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, State Key Laboratory of Medical Neurobiology and Institutes of Brain Science, Zhongshan Hospital, Fudan University, Shanghai, China

    Shi-Jun Weng, Wei-Yi Chen & Xiong-Li Yang

  2. Department of Biology, University of Akron, Akron, OH, USA

    Jordan M. Renna

Authors
  1. Shi-Jun Weng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jordan M. Renna
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wei-Yi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiong-Li Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shi-Jun Weng .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, University Hospital Schleswig-Holstein, Kiel, Germany

    Naoyuki Tanimoto

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Weng, SJ., Renna, J.M., Chen, WY., Yang, XL. (2018). Functional Assessment of Melanopsin-Driven Light Responses in the Mouse: Multielectrode Array Recordings. In: Tanimoto, N. (eds) Mouse Retinal Phenotyping. Methods in Molecular Biology, vol 1753. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7720-8_20

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-7720-8_20

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7719-2

  • Online ISBN: 978-1-4939-7720-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation