April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Spontaneous Hyperactivity Emerges Before Light Responsiveness Is Lost During Retinal Degeneration In rd10 Mice
Author Affiliations & Notes
  • S. F. Stasheff
    Pediatrics (Neurology), University of Iowa, Iowa City, Iowa
  • M. P. Andrews
    Pediatrics (Neurology), University of Iowa, Iowa City, Iowa
  • Footnotes
    Commercial Relationships  S.F. Stasheff, None; M.P. Andrews, None.
  • Footnotes
    Support  Child Neurology Foundation, Lewis-Rhodes Charitable Trust
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 5686. doi:
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      S. F. Stasheff, M. P. Andrews; Spontaneous Hyperactivity Emerges Before Light Responsiveness Is Lost During Retinal Degeneration In rd10 Mice. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5686.

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

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Purpose: : I previously reported that both spontaneous and light-evoked ganglion cell activity are substantially altered as photoreceptors degenerate in the retinal degeneration (rd1) mouse, suggesting significant reorganization of inner retinal circuitry. In the closely related rd10 mouse degeneration progresses more slowly, so loss of photoreceptors begins only after a peak of developmental plasticity in retinal circuitry. Comparison of these two models provides an opportunity to determine whether changes in spontaneous versus light-evoked activity stem from distinct mechanisms, and whether underlying circuit reorganization reflects perturbations of normal retinal development.

Methods: : Extracellular action potentials were recorded simultaneously from 30-90 retinal ganglion cells in the in vitro retina of wild type (wt), rd1 or rd10 mice, using a multielectrode array. Spontaneous activity was monitored and full field light flashes were presented to retinas of various developmental ages.

Results: : Developmental spontaneous "waves" of correlated ganglion cell activity, comparable to those in wt mice, are present in rd1 and rd10 retinas prior to eye opening (P7-8). In rd1 mice, spontaneous firing increases by postnatal day 14-15 (P14-15) and reaches ~10 times normal by P28, when all responses to light have disappeared. In rd10 retinas, spontaneous activity already has increased substantially by P14-15, yet vigorous ON and OFF responses are maintained up to at least P28, and are not completely lost until after P38.

Conclusions: : Despite a similar genetic defect as in rd1 mice, in rd10 retinas normal developmental processes form and maintain light-evoked activity for an extended period. Nonetheless, spontaneous hyperactivity emerges in a manner similar to that in rd1. Thus, developmental mechanisms appear not to contribute substantially to the emergence of hyperactivity in these models. Furthermore, mechanisms underlying the hyperactivity appear separable from those that alter light-driven responses. This raises hope that normal visual function might be preserved or restored even in the face of ganglion cell hyperactivity seen in inherited retinal degenerations.

Keywords: retinal degenerations: cell biology • ganglion cells • electrophysiology: non-clinical 

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