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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

Calcium signals underlying two distinct oscillators. (A) Isolated low-frequency EPSC oscillations recorded from identified wt (top) and rd1 (bottom) GCs were eliminated by a non-selective voltage-gated Ca2+ channel blocker, CdCl2 (200 μM). (B) Bipolar cell-mediated oscillations were slightly reduced by mibefradil (5 μM), a selective T-type voltage-gated Ca2+-channel blocker, and completely abolished by nifedipine (30 μM), a selective L-type voltage-gated Ca2+-channel blocker, in both wt (top) and rd1 (bottom) GCs. (C) Ca2+ influx is required for amacrine cell-mediated high-frequency oscillations in rd1. In representative rd1 GCs, both oscillatory EPSCs and IPSCs were eliminated by CdCl2 (200 μM). Summary histograms are shown in Figure 6. In confocal images, scale bars are adjusted to 40 μm.
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Figure 8: Calcium signals underlying two distinct oscillators. (A) Isolated low-frequency EPSC oscillations recorded from identified wt (top) and rd1 (bottom) GCs were eliminated by a non-selective voltage-gated Ca2+ channel blocker, CdCl2 (200 μM). (B) Bipolar cell-mediated oscillations were slightly reduced by mibefradil (5 μM), a selective T-type voltage-gated Ca2+-channel blocker, and completely abolished by nifedipine (30 μM), a selective L-type voltage-gated Ca2+-channel blocker, in both wt (top) and rd1 (bottom) GCs. (C) Ca2+ influx is required for amacrine cell-mediated high-frequency oscillations in rd1. In representative rd1 GCs, both oscillatory EPSCs and IPSCs were eliminated by CdCl2 (200 μM). Summary histograms are shown in Figure 6. In confocal images, scale bars are adjusted to 40 μm.

Mentions: Oscillations in rd1 ACs and variable effect of gap junction blocker on fast oscillations in rd1 GCs. (A) Representative IPSCs from rd1 narrow- and wide-field amacrine cells. (B) Oscillations that persisted in amacrine cells following application of iGluR antagonists did not differ from control conditions (p = 0.19, n = 5, paired t-test). (C,D) Recordings of oscillatory activity in two representative GCs. Application of the gap junction blocker carbenoxolone (CBX, 100 μM) diminishes oscillatory activity in one cell (C), while this activity remained unaffected in another cell (D). In both cells, all high-frequency oscillatory activity was abolished following addition of blockers of inhibitory transmission. Large, low-frequency EPSCs remain [(D), right traces], which are driven by bipolar cells (as shown in Figures 6–8).


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

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

Calcium signals underlying two distinct oscillators. (A) Isolated low-frequency EPSC oscillations recorded from identified wt (top) and rd1 (bottom) GCs were eliminated by a non-selective voltage-gated Ca2+ channel blocker, CdCl2 (200 μM). (B) Bipolar cell-mediated oscillations were slightly reduced by mibefradil (5 μM), a selective T-type voltage-gated Ca2+-channel blocker, and completely abolished by nifedipine (30 μM), a selective L-type voltage-gated Ca2+-channel blocker, in both wt (top) and rd1 (bottom) GCs. (C) Ca2+ influx is required for amacrine cell-mediated high-frequency oscillations in rd1. In representative rd1 GCs, both oscillatory EPSCs and IPSCs were eliminated by CdCl2 (200 μM). Summary histograms are shown in Figure 6. In confocal images, scale bars are adjusted to 40 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3285818&req=5

Figure 8: Calcium signals underlying two distinct oscillators. (A) Isolated low-frequency EPSC oscillations recorded from identified wt (top) and rd1 (bottom) GCs were eliminated by a non-selective voltage-gated Ca2+ channel blocker, CdCl2 (200 μM). (B) Bipolar cell-mediated oscillations were slightly reduced by mibefradil (5 μM), a selective T-type voltage-gated Ca2+-channel blocker, and completely abolished by nifedipine (30 μM), a selective L-type voltage-gated Ca2+-channel blocker, in both wt (top) and rd1 (bottom) GCs. (C) Ca2+ influx is required for amacrine cell-mediated high-frequency oscillations in rd1. In representative rd1 GCs, both oscillatory EPSCs and IPSCs were eliminated by CdCl2 (200 μM). Summary histograms are shown in Figure 6. In confocal images, scale bars are adjusted to 40 μm.
Mentions: Oscillations in rd1 ACs and variable effect of gap junction blocker on fast oscillations in rd1 GCs. (A) Representative IPSCs from rd1 narrow- and wide-field amacrine cells. (B) Oscillations that persisted in amacrine cells following application of iGluR antagonists did not differ from control conditions (p = 0.19, n = 5, paired t-test). (C,D) Recordings of oscillatory activity in two representative GCs. Application of the gap junction blocker carbenoxolone (CBX, 100 μM) diminishes oscillatory activity in one cell (C), while this activity remained unaffected in another cell (D). In both cells, all high-frequency oscillatory activity was abolished following addition of blockers of inhibitory transmission. Large, low-frequency EPSCs remain [(D), right traces], which are driven by bipolar cells (as shown in Figures 6–8).

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