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Network deficiency exacerbates impairment in a mouse model of retinal degeneration.

Yee CW, Toychiev AH, Sagdullaev BT - Front Syst Neurosci (2012)

Bottom Line: In recording from retina in a mouse model of retinal degeneration (RD), we found that the incidence of oscillatory activity varied across different cell classes, evidence that some retinal networks are more affected by functional changes than others.By stimulating the surviving circuitry at different stages of the neurodegenerative process, we found that this dystrophic oscillator further compromises the function of the retina.These data reveal that retinal remodeling can exacerbate the visual deficit, and that aberrant synaptic activity could be targeted for RD treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Burke Medical Research Institute, Weill Medical College of Cornell University White Plains, NY, USA.

ABSTRACT
Neural oscillations play an important role in normal brain activity, but also manifest during Parkinson's disease, epilepsy, and other pathological conditions. The contribution of these aberrant oscillations to the function of the surviving brain remains unclear. In recording from retina in a mouse model of retinal degeneration (RD), we found that the incidence of oscillatory activity varied across different cell classes, evidence that some retinal networks are more affected by functional changes than others. This aberrant activity was driven by an independent inhibitory amacrine cell oscillator. By stimulating the surviving circuitry at different stages of the neurodegenerative process, we found that this dystrophic oscillator further compromises the function of the retina. These data reveal that retinal remodeling can exacerbate the visual deficit, and that aberrant synaptic activity could be targeted for RD treatment.

No MeSH data available.


Related in: MedlinePlus

Aberrant activity compromises efficiency of synaptic transmission within the inner retina during RD. (A) Photoreceptor-dependent light-evoked spiking responses from GCs in rd1 and age-matched wt controls (P20–P26). Peristimulus time histograms (PSTHs) were generated with 0.1 ms bins. The recording paradigm is illustrated in the insert (PR, photoreceptor; BC, bipolar; AC, amacrine; GC, ganglion cells). Shaded area – timing of the light stimulus (∼300 μm light spot). (B) Photoreceptor-independent synaptically evoked activity from voltage-clamped GCs in rd1 mice at different phases of retinal remodeling and age-matched wildtype controls. A current pulse was delivered to the INL, bypassing photoreceptors. Arrowhead indicates stimulus artifact. (C) Signal-to-noise ratios at different ages in rd1 (black bars, n = 21) and wt (gray bars, n = 15). As RD progresses, increasing noise levels obscure the evoked response. All data are reported as means ± SEM; p < 0.001.
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Figure 9: Aberrant activity compromises efficiency of synaptic transmission within the inner retina during RD. (A) Photoreceptor-dependent light-evoked spiking responses from GCs in rd1 and age-matched wt controls (P20–P26). Peristimulus time histograms (PSTHs) were generated with 0.1 ms bins. The recording paradigm is illustrated in the insert (PR, photoreceptor; BC, bipolar; AC, amacrine; GC, ganglion cells). Shaded area – timing of the light stimulus (∼300 μm light spot). (B) Photoreceptor-independent synaptically evoked activity from voltage-clamped GCs in rd1 mice at different phases of retinal remodeling and age-matched wildtype controls. A current pulse was delivered to the INL, bypassing photoreceptors. Arrowhead indicates stimulus artifact. (C) Signal-to-noise ratios at different ages in rd1 (black bars, n = 21) and wt (gray bars, n = 15). As RD progresses, increasing noise levels obscure the evoked response. All data are reported as means ± SEM; p < 0.001.

Mentions: In rd1 mice at P20–26, light-induced responses could be observed (Figure 9A). At this stage, the majority of rods have died, while cones are still present in large numbers (Strettoi and Pignatelli, 2000). In light-adapted conditions (see Materials and Methods), responses are not evident in individual traces, but are observable in peristimulus time histograms (PSTHs) and averages. However, using light stimuli does not enable the separation of the relative contributions of photoreceptor and post-photoreceptor sites to diminished responses in RD.


Network deficiency exacerbates impairment in a mouse model of retinal degeneration.

Yee CW, Toychiev AH, Sagdullaev BT - Front Syst Neurosci (2012)

Aberrant activity compromises efficiency of synaptic transmission within the inner retina during RD. (A) Photoreceptor-dependent light-evoked spiking responses from GCs in rd1 and age-matched wt controls (P20–P26). Peristimulus time histograms (PSTHs) were generated with 0.1 ms bins. The recording paradigm is illustrated in the insert (PR, photoreceptor; BC, bipolar; AC, amacrine; GC, ganglion cells). Shaded area – timing of the light stimulus (∼300 μm light spot). (B) Photoreceptor-independent synaptically evoked activity from voltage-clamped GCs in rd1 mice at different phases of retinal remodeling and age-matched wildtype controls. A current pulse was delivered to the INL, bypassing photoreceptors. Arrowhead indicates stimulus artifact. (C) Signal-to-noise ratios at different ages in rd1 (black bars, n = 21) and wt (gray bars, n = 15). As RD progresses, increasing noise levels obscure the evoked response. All data are reported as means ± SEM; p < 0.001.
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Related In: Results  -  Collection

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Figure 9: Aberrant activity compromises efficiency of synaptic transmission within the inner retina during RD. (A) Photoreceptor-dependent light-evoked spiking responses from GCs in rd1 and age-matched wt controls (P20–P26). Peristimulus time histograms (PSTHs) were generated with 0.1 ms bins. The recording paradigm is illustrated in the insert (PR, photoreceptor; BC, bipolar; AC, amacrine; GC, ganglion cells). Shaded area – timing of the light stimulus (∼300 μm light spot). (B) Photoreceptor-independent synaptically evoked activity from voltage-clamped GCs in rd1 mice at different phases of retinal remodeling and age-matched wildtype controls. A current pulse was delivered to the INL, bypassing photoreceptors. Arrowhead indicates stimulus artifact. (C) Signal-to-noise ratios at different ages in rd1 (black bars, n = 21) and wt (gray bars, n = 15). As RD progresses, increasing noise levels obscure the evoked response. All data are reported as means ± SEM; p < 0.001.
Mentions: In rd1 mice at P20–26, light-induced responses could be observed (Figure 9A). At this stage, the majority of rods have died, while cones are still present in large numbers (Strettoi and Pignatelli, 2000). In light-adapted conditions (see Materials and Methods), responses are not evident in individual traces, but are observable in peristimulus time histograms (PSTHs) and averages. However, using light stimuli does not enable the separation of the relative contributions of photoreceptor and post-photoreceptor sites to diminished responses in RD.

Bottom Line: In recording from retina in a mouse model of retinal degeneration (RD), we found that the incidence of oscillatory activity varied across different cell classes, evidence that some retinal networks are more affected by functional changes than others.By stimulating the surviving circuitry at different stages of the neurodegenerative process, we found that this dystrophic oscillator further compromises the function of the retina.These data reveal that retinal remodeling can exacerbate the visual deficit, and that aberrant synaptic activity could be targeted for RD treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Burke Medical Research Institute, Weill Medical College of Cornell University White Plains, NY, USA.

ABSTRACT
Neural oscillations play an important role in normal brain activity, but also manifest during Parkinson's disease, epilepsy, and other pathological conditions. The contribution of these aberrant oscillations to the function of the surviving brain remains unclear. In recording from retina in a mouse model of retinal degeneration (RD), we found that the incidence of oscillatory activity varied across different cell classes, evidence that some retinal networks are more affected by functional changes than others. This aberrant activity was driven by an independent inhibitory amacrine cell oscillator. By stimulating the surviving circuitry at different stages of the neurodegenerative process, we found that this dystrophic oscillator further compromises the function of the retina. These data reveal that retinal remodeling can exacerbate the visual deficit, and that aberrant synaptic activity could be targeted for RD treatment.

No MeSH data available.


Related in: MedlinePlus