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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

Recording procedures and identification of GCs in RD retinal wholemount. Top. The view at the retinal ganglion cell (GC) layer in wholemount retinal preparation. The outlines of individual cell bodies are visible across the field. The recording pipette is targeting one of the GCs (asterisk). Fluorescent image of the same GC with attached recording pipette filled with sulforhodamine B (monochrome image). GCs were distinguished from displaced amacrine cells by the presence of an axon (arrowhead). Following the characterization of excitatory (EPSCs) and inhibitory (IPSCs) inputs and spiking output, the pipette was detached and the detailed dendritic structure was reconstructed using confocal microscopy. A z-stack of 161 images was acquired at 0.5 μm steps at 1024 × 1024 pixel resolution. A nuclear stain (Ethidium Bromide with To-Pro-3, blue) was subsequently added to aid in determining the thickness of the inner plexiform layer (IPL). Scale bar – 20 μm. Bottom. (Left) Spikes and currents recorded from the same cell. (Middle) Arbor area and (Right) depth of the dendritic arbors (AD) were measured as illustrated.
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Figure 1: Recording procedures and identification of GCs in RD retinal wholemount. Top. The view at the retinal ganglion cell (GC) layer in wholemount retinal preparation. The outlines of individual cell bodies are visible across the field. The recording pipette is targeting one of the GCs (asterisk). Fluorescent image of the same GC with attached recording pipette filled with sulforhodamine B (monochrome image). GCs were distinguished from displaced amacrine cells by the presence of an axon (arrowhead). Following the characterization of excitatory (EPSCs) and inhibitory (IPSCs) inputs and spiking output, the pipette was detached and the detailed dendritic structure was reconstructed using confocal microscopy. A z-stack of 161 images was acquired at 0.5 μm steps at 1024 × 1024 pixel resolution. A nuclear stain (Ethidium Bromide with To-Pro-3, blue) was subsequently added to aid in determining the thickness of the inner plexiform layer (IPL). Scale bar – 20 μm. Bottom. (Left) Spikes and currents recorded from the same cell. (Middle) Arbor area and (Right) depth of the dendritic arbors (AD) were measured as illustrated.

Mentions: Each GC was filled with sulforhodamine B, included in patch pipette solution. At the end of each recording session, contrast and fluorescent images of the cell were documented with a modified Nikon D5000 DSLR attached to a Nikon FN1 microscope. The preparation was immediately placed in glass bottom culture dish (Matek, Ashland, MA, USA) and transferred to a stage of a Nikon C1 confocal microscope. A z-stack of 160 images was acquired at 0.5 μm steps at a resolution of 1024 × 1024 pixels. A nuclear stain stock solution, 2 μL of an equal mixture of 12 mM ethidium bromide and 100 μM To-Pro-3 (Invitrogen, Carlsbad, CA, USA) was added for determining the borders of the inner plexiform layer (IPL, Figure 1). GCs were distinguished from displaced ACs by the presence of an axon. As previously described (Sun et al., 2002), for dendritic field (DF) size, a polygon was drawn by linking the tips of dendrites, and the area calculated. The area was converted back to diameter by assuming a circular DF. Cell body size was measured similarly. The level at which the GC dendritic processes stratified in the IPL was measured as the distance of its processes from the proximal (0%) to distal margin (100%) of the IPL. In general, ON GCs were defined as those whose dendrites stratified <60% of the IPL depth, and OFF GCs stratified >60% of the IPL depth. Measurement of cell properties was performed with ImageJ and Nikon EZ-C1 software. Cells were classified under two different methods. First, cell body size, DF diameter, and depth of dendritic stratification were used to classify cells in adherence to the groups described by Sun et al. (2002). This was done to verify a broad sampling of previously identified classes in both wild type (Sun et al., 2002) and RD (Mazzoni et al., 2008) GCs, and to establish a baseline for cluster analysis (Kong et al., 2005). Second, a cluster analysis was performed using SPSS (SPSS Inc., Chicago, IL, USA), with stratification depth and DF diameter as parameters (Badea and Nathans, 2004; Kong et al., 2005). This followed the method described by Badea and Nathans: Ward’s joining method was used to determine the number of clusters by a separation threshold of 25% of the greatest distance between nodes, followed by a k-means analysis to determine cluster membership. Monostratified and bistratified cells were analyzed separately. For bistratified cells, the dendritic depth and the area were obtained for both branches.


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

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

Recording procedures and identification of GCs in RD retinal wholemount. Top. The view at the retinal ganglion cell (GC) layer in wholemount retinal preparation. The outlines of individual cell bodies are visible across the field. The recording pipette is targeting one of the GCs (asterisk). Fluorescent image of the same GC with attached recording pipette filled with sulforhodamine B (monochrome image). GCs were distinguished from displaced amacrine cells by the presence of an axon (arrowhead). Following the characterization of excitatory (EPSCs) and inhibitory (IPSCs) inputs and spiking output, the pipette was detached and the detailed dendritic structure was reconstructed using confocal microscopy. A z-stack of 161 images was acquired at 0.5 μm steps at 1024 × 1024 pixel resolution. A nuclear stain (Ethidium Bromide with To-Pro-3, blue) was subsequently added to aid in determining the thickness of the inner plexiform layer (IPL). Scale bar – 20 μm. Bottom. (Left) Spikes and currents recorded from the same cell. (Middle) Arbor area and (Right) depth of the dendritic arbors (AD) were measured as illustrated.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 1: Recording procedures and identification of GCs in RD retinal wholemount. Top. The view at the retinal ganglion cell (GC) layer in wholemount retinal preparation. The outlines of individual cell bodies are visible across the field. The recording pipette is targeting one of the GCs (asterisk). Fluorescent image of the same GC with attached recording pipette filled with sulforhodamine B (monochrome image). GCs were distinguished from displaced amacrine cells by the presence of an axon (arrowhead). Following the characterization of excitatory (EPSCs) and inhibitory (IPSCs) inputs and spiking output, the pipette was detached and the detailed dendritic structure was reconstructed using confocal microscopy. A z-stack of 161 images was acquired at 0.5 μm steps at 1024 × 1024 pixel resolution. A nuclear stain (Ethidium Bromide with To-Pro-3, blue) was subsequently added to aid in determining the thickness of the inner plexiform layer (IPL). Scale bar – 20 μm. Bottom. (Left) Spikes and currents recorded from the same cell. (Middle) Arbor area and (Right) depth of the dendritic arbors (AD) were measured as illustrated.
Mentions: Each GC was filled with sulforhodamine B, included in patch pipette solution. At the end of each recording session, contrast and fluorescent images of the cell were documented with a modified Nikon D5000 DSLR attached to a Nikon FN1 microscope. The preparation was immediately placed in glass bottom culture dish (Matek, Ashland, MA, USA) and transferred to a stage of a Nikon C1 confocal microscope. A z-stack of 160 images was acquired at 0.5 μm steps at a resolution of 1024 × 1024 pixels. A nuclear stain stock solution, 2 μL of an equal mixture of 12 mM ethidium bromide and 100 μM To-Pro-3 (Invitrogen, Carlsbad, CA, USA) was added for determining the borders of the inner plexiform layer (IPL, Figure 1). GCs were distinguished from displaced ACs by the presence of an axon. As previously described (Sun et al., 2002), for dendritic field (DF) size, a polygon was drawn by linking the tips of dendrites, and the area calculated. The area was converted back to diameter by assuming a circular DF. Cell body size was measured similarly. The level at which the GC dendritic processes stratified in the IPL was measured as the distance of its processes from the proximal (0%) to distal margin (100%) of the IPL. In general, ON GCs were defined as those whose dendrites stratified <60% of the IPL depth, and OFF GCs stratified >60% of the IPL depth. Measurement of cell properties was performed with ImageJ and Nikon EZ-C1 software. Cells were classified under two different methods. First, cell body size, DF diameter, and depth of dendritic stratification were used to classify cells in adherence to the groups described by Sun et al. (2002). This was done to verify a broad sampling of previously identified classes in both wild type (Sun et al., 2002) and RD (Mazzoni et al., 2008) GCs, and to establish a baseline for cluster analysis (Kong et al., 2005). Second, a cluster analysis was performed using SPSS (SPSS Inc., Chicago, IL, USA), with stratification depth and DF diameter as parameters (Badea and Nathans, 2004; Kong et al., 2005). This followed the method described by Badea and Nathans: Ward’s joining method was used to determine the number of clusters by a separation threshold of 25% of the greatest distance between nodes, followed by a k-means analysis to determine cluster membership. Monostratified and bistratified cells were analyzed separately. For bistratified cells, the dendritic depth and the area were obtained for both branches.

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