June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Three blind mice, see how they run: Light-dependent behavior in the absence of an optic nerve
Author Affiliations & Notes
  • Anna Matynia
    Jules Stein Eye Institute, UCLA, Los Angeles, California, United States
  • Sachin Parikh
    Jules Stein Eye Institute, UCLA, Los Angeles, California, United States
  • Steven Nusinowitz
    Jules Stein Eye Institute, UCLA, Los Angeles, California, United States
  • Michael B Gorin
    Jules Stein Eye Institute, UCLA, Los Angeles, California, United States
  • Footnotes
    Commercial Relationships   Anna Matynia, None; Sachin Parikh, None; Steven Nusinowitz, None; Michael Gorin, None
  • Footnotes
    Support  Knights Templar Eye Foundation, Gerald Oppenheimer Family Foundation
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4126. doi:
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    • Get Citation

      Anna Matynia, Sachin Parikh, Steven Nusinowitz, Michael B Gorin; Three blind mice, see how they run: Light-dependent behavior in the absence of an optic nerve. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4126.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The retinohypothalamic tract is critical for light-dependent responses that drive behavior although light aversion and light-induced blinks have been observed in the absence of a functional optic nerve. This study investigates the role of the optic and trigeminal nerves in light aversion.

Methods : Light aversion was assessed in adult mice using an aversion index (AI: ≤0=no aversion; 1=complete aversion). Wild type mice (WT) or mice lacking melanopsin expressing cells (OPN4dta/dta) were subjected to either bilateral sham or one of three optic nerve manipulations that result in “blindness”: severe Optic Nerve Crush (ONC), Optic Nerve Transection (ONT) or ciliary Trigeminal and Optic nerve, ophthalmic Artery and Sheath Transection (TOAST). OPN4dta/dta rd1 mice lacking all known photoreceptors were also assessed. Administration of morphine (5mg/kg) or nitroglycerin (NTG, 10mg/kg) was used to unmask light aversion.

Results : Without drug treatment, all WT mice with optic nerve injury (ONC, ONT, TOAST) exhibited no light aversion at 1000 Lux. Light aversion increased in WT sham mice after NTG (AI=0.79±0.09, n=8) or morphine (AI=0.98±0.01, n=8). NTG also increased light aversion in severe bilateral ONC (AI=0.46±0.16, n=8), ONT (AI=0.37±0.24, n=4) and TOAST mice (AI=0.43±0.17, n=3). Neither OPN4dta/dta with ONC (AI=0.19±0.22, n=8) nor OPN4dta/dta rd1 double mutants (AI=0.12±0.02, n=4) showed NTG-induced light aversion. Morphine similarly increased light aversion in WT mice with ONC (AI=0.39±0.05, n=8), ONT (AI=0.58±0.15, n=4) or TOAST (AI=0.58±0.21, n=3). By contrast to NTG, morphine induced light aversion in OPN4dta/dta with ONC (AI=0.41±0.08, n=8) and OPN4dta/dta rd1 double mutants (AI=0.46±0.09, n=4). Both retinal (ipRGCs) and trigeminal ganglion melanopsin-expressing neurons in OPN4dta/dta mice are ablated.

Conclusions : Light perception mediating behavioral responses can occur in the absence of the optic nerve and ensheathed trigeminal nerves. Morphine and NTG provide useful tools for identifying the neural circuit(s) underlying this latent light perception. Melanopsin expression has been observed in a subset of trigeminal ganglion neurons that respond to light ex vivo, providing a potential alternative circuit to influence light aversion. Other mechanisms for light dependent behavior in the absence of trigeminal or optic nerve innervation must also be considered.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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