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G. Zeck, J. Menzler; Network Oscillation in Rod Degenerated (rd1) Retinas. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5799.
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The mouse retina represents an ideal model to study alterations in the physiological activity after the loss of one cell class, the photoreceptors . It has been reported that spontaneous ganglion cell activity increases  and becomes rhythmic in the retinal degeneration (rd1) mouse [3-4]. The goal of this study is to explore mechanisms leading to oscillatory activity and the spatial scale over which it occurs.
Extracellular action potentials were recorded simultaneously from up to 100 retinal ganglion cells (RGC) in the in vitro retina of rd1 and wild type (wt), using a multi-transistor array with 16384 sensor sites. Spontaneous spiking activity and sub-threshold oscillations were monitored at micron scale spatial resolution in adult retinas (P40 - P130).
In rd1 retinas the spike trains of more than 80 % of the RGCs positively correlate with each other as compared to less than 30% in wt retinas. For rd1 RGCs the cross-correlogram displays multiple peaks, indicating a fundamental spiking frequency of ~ 10 Hz. Most of the correlated activity, both in rd1 and wt occurs between neurons separated less than 300 µm from each other.In rd1 retinas we measured an oscillatory Local Field Potential (LFP). Power Spectral Density analysis revealed that the LFP fundamental frequency was in the same frequency range as the RGC spiking activity. The LFPs are spatially restricted to areas smaller 0.5 mm2 and propagate across short retinal distances (<500 µm).Pharmacological treatment helps to confine the putative players acting as the driving source. The sodium channel blocker TTX abolishes RGC spiking but not the LFP. Glutamate receptor blockers (DNQX, AP-7) inhibited the LFPs but not the spiking activity. Application of inhibitory receptor blockers (strychnine, SR 95531) increased the LFP amplitude and decreased the oscillation frequency. Inhibition of electrical synapses by a gap junction blocker abolishes the LFPs as well.
Our results indicate that photoreceptor degeneration leads to prominent changes in the physiological activity of the majority of ganglion cells. A rhythmic and glutamate sensitive oscillatory driving force leads to oscillatory RGC spiking activity. Because the rhythmic activity occurs in phase across restricted retinal areas it may explain some of the photopsias reported by patients diagnosed with retinis pigmentosa.1. Marc, R.E., et al. Progr. Ret. Eye Res. 22, 607-655 (2003).2. Stasheff, SF et al. J. Neurophysiol 99, 1408 - 1421 (2008).3. Margolis, D.J., et al. J. Neurosci 28, 6526-6536 (2008).4. Ye, J.H. & Goo, Y.S. Physiol. Measurement 28, 1079-1088 (2007).
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