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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

Dystrophic amacrine cell input drives bursting activity in RD. Diagrams of the synaptic interactions in rd1 (left) and wt (right) retinas. Bipolar cells (BC) provide excitatory drive to ganglion cells (GC) and amacrine cells (AC). Amacrine cells, in turn, modulate the GC activity via presynaptic inhibition of BCs, and direct inhibition of GCs. In both RD and healthy retina, an intrinsic slow BC oscillator is silent in resting conditions. In rd1 retina, an additional fast dystrophic AC oscillator is active, and affects both BC and GC output. Lower panels show GC spiking output at different conditions. In control conditions, GCs in RD retina show fast bursting activity driven by the AC oscillator. This fast bursting persists with nifedipine. In contrast, application of inhibitory blockers (STR + GZ + TPMPA) unveils the BC oscillator, which is present in both rd1 and wt, but silent in control conditions. Unlike fast oscillations this slow oscillator is abolished by nifedipine.
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Figure 10: Dystrophic amacrine cell input drives bursting activity in RD. Diagrams of the synaptic interactions in rd1 (left) and wt (right) retinas. Bipolar cells (BC) provide excitatory drive to ganglion cells (GC) and amacrine cells (AC). Amacrine cells, in turn, modulate the GC activity via presynaptic inhibition of BCs, and direct inhibition of GCs. In both RD and healthy retina, an intrinsic slow BC oscillator is silent in resting conditions. In rd1 retina, an additional fast dystrophic AC oscillator is active, and affects both BC and GC output. Lower panels show GC spiking output at different conditions. In control conditions, GCs in RD retina show fast bursting activity driven by the AC oscillator. This fast bursting persists with nifedipine. In contrast, application of inhibitory blockers (STR + GZ + TPMPA) unveils the BC oscillator, which is present in both rd1 and wt, but silent in control conditions. Unlike fast oscillations this slow oscillator is abolished by nifedipine.

Mentions: Until recently, RD has mainly been considered to be a deficiency of photoreceptors. We studied a form of “network deficiency” – maladaptive changes within the surviving tissue – that manifests as aberrant oscillatory activity. Incidence and properties of these oscillations varied between GC classes, suggesting differences between visual pathways in susceptibility to retinal remodeling. Single-cell recordings combined with pharmacological analysis allowed us to distinguish two independent oscillators in the RD retina, driven respectively by bipolar and amacrine cells. In contrast to earlier studies (Borowska et al., 2011; Menzler and Zeck, 2011), we find that an AC oscillator alone is necessary and sufficient to drive aberrant activity in rd1 retina. A BC oscillator, in both rd1 and wt, is normally suppressed by inhibition and not required for aberrant activity (Figure 10). We find that aberrant activity compromises transmission of evoked responses in surviving inner retina, exacerbating the visual deficit.


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

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

Dystrophic amacrine cell input drives bursting activity in RD. Diagrams of the synaptic interactions in rd1 (left) and wt (right) retinas. Bipolar cells (BC) provide excitatory drive to ganglion cells (GC) and amacrine cells (AC). Amacrine cells, in turn, modulate the GC activity via presynaptic inhibition of BCs, and direct inhibition of GCs. In both RD and healthy retina, an intrinsic slow BC oscillator is silent in resting conditions. In rd1 retina, an additional fast dystrophic AC oscillator is active, and affects both BC and GC output. Lower panels show GC spiking output at different conditions. In control conditions, GCs in RD retina show fast bursting activity driven by the AC oscillator. This fast bursting persists with nifedipine. In contrast, application of inhibitory blockers (STR + GZ + TPMPA) unveils the BC oscillator, which is present in both rd1 and wt, but silent in control conditions. Unlike fast oscillations this slow oscillator is abolished by nifedipine.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
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Figure 10: Dystrophic amacrine cell input drives bursting activity in RD. Diagrams of the synaptic interactions in rd1 (left) and wt (right) retinas. Bipolar cells (BC) provide excitatory drive to ganglion cells (GC) and amacrine cells (AC). Amacrine cells, in turn, modulate the GC activity via presynaptic inhibition of BCs, and direct inhibition of GCs. In both RD and healthy retina, an intrinsic slow BC oscillator is silent in resting conditions. In rd1 retina, an additional fast dystrophic AC oscillator is active, and affects both BC and GC output. Lower panels show GC spiking output at different conditions. In control conditions, GCs in RD retina show fast bursting activity driven by the AC oscillator. This fast bursting persists with nifedipine. In contrast, application of inhibitory blockers (STR + GZ + TPMPA) unveils the BC oscillator, which is present in both rd1 and wt, but silent in control conditions. Unlike fast oscillations this slow oscillator is abolished by nifedipine.
Mentions: Until recently, RD has mainly been considered to be a deficiency of photoreceptors. We studied a form of “network deficiency” – maladaptive changes within the surviving tissue – that manifests as aberrant oscillatory activity. Incidence and properties of these oscillations varied between GC classes, suggesting differences between visual pathways in susceptibility to retinal remodeling. Single-cell recordings combined with pharmacological analysis allowed us to distinguish two independent oscillators in the RD retina, driven respectively by bipolar and amacrine cells. In contrast to earlier studies (Borowska et al., 2011; Menzler and Zeck, 2011), we find that an AC oscillator alone is necessary and sufficient to drive aberrant activity in rd1 retina. A BC oscillator, in both rd1 and wt, is normally suppressed by inhibition and not required for aberrant activity (Figure 10). We find that aberrant activity compromises transmission of evoked responses in surviving inner retina, exacerbating the visual deficit.

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