Proceedings of The Physiological Society

Physiology 2015 (Cardiff, UK) (2015) Proc Physiol Soc 34, C67

Oral Communications

Plasticity of visual cortex function in an adult mouse model of retinal ganglion cell loss

A. Vasalauskaite1,2, J. Morgan2, F. Sengpiel1

1. School of Biosciences, Cardiff University, Cardiff, United Kingdom. 2. School of Optometry & Vision Sciences, Cardiff University, Cardiff, United Kingdom.

Injury to optic nerve (ON) axons plays a major role in glaucoma progression. ON crush is an established model of an acute unilateral axonal injury. The crush results in retrograde degeneration and death of retinal ganglion cells (RGCs). However it is unknown how signal transmission to higher visual structures such as primary visual cortex (V1) is affected. Separate cohorts of C57BL/6 mice of >8 month old were used for this study. Unilateral ON crush was performed on left eyes under general anaesthesia (2 % isoflurane). V1 function of the contralateral (right) hemisphere was assessed by optical imaging (OI) under anaesthesia (0.8-1.0% isoflurane) of normal adult mice (n=6) and 30min (n=2), 7d (n=3), 14d (n=1) and 30 days (n=3) after ON crush. RGC numbers were quantified by counting Hoechst labelled cells in flat-mounted retinas. An additional group of mice (n=5) were imaged longitudinally by optical imaging (OI) before and at multiple time points up to 60 days after ON crush. We found a significant (p<0.001) cell loss in the RGC layer compared to normal adults after 30 days ON crush. RGC layer cell loss occurred progressively over time with 15% of cells lost after 7 days and 43% of cells lost 14 days after ON crush. OI experiments demonstrate a significant shift in ocular dominance index (p<0.001) from 0.17±0.04 to -0.67±0.12 towards the ipsilateral eye and significant reduction (p<0.001) of signal magnitude in V1 in response to contralateral eye stimulation from 0.79±0.08 in normal adult control to 0.15±0.05 in all ON crush animals. Surprisingly response magnitude to ipsilateral eye stimulation was significantly increased (p<0.05) from 0.55±0.08 to 0.72 ±0.15 after long term ON crush (n=7). This study shows an acute and permanent loss of signal transmission from the retina to V1 via a crushed ON and much slower RGC loss. Additionally we demonstrate a significant increase of responsiveness in V1 to non-crushed eye stimulation, which indicates that acute and severe injury of the ON in adulthood may evoke plasticity that is normally seen during the critical period of visual cortex development.

Where applicable, experiments conform with Society ethical requirements