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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

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).
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Figure 5: 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).

Mentions: CNQX and D-AP5 eliminated EPSCs in all rd1 GCs. Oscillatory IPSCs, in contrast, persisted in a large subset of GCs and were abolished after the addition of strychnine (3 μM), gabazine (5 μM) and TPMPA (100 μM), antagonists of glycine-, GABAA-, and GABACRs, respectively (Figure 4A). As evident from FFT heat maps (right panel), oscillations not only persisted, but were refined in a subset of GCs, showing less inter-wave variation in amplitude and frequency, reflected as an increase in power (p = 0.02, n = 11, paired t-test; Figure 4D). Notably, OFF cells all increased in power, while ON cells varied, though most maintained oscillations at reduced power (r2 = 0.67, p < 0.001, n = 26, linear regression; Figure 4C). The persistence of fast aberrant activity in a diversity of GCs suggests that BCs are not the source. An alternate pathway for these oscillations may be gap junction-mediated pathway between BCs and AII cells, which have been suggested to be required for their generation (Borowska et al., 2011) and/or propagation across the retina (Menzler and Zeck, 2011). For rd1 GCs with IPSC oscillations resistant to CNQX and DAP-5, the subsequent addition of the gap junction blocker carbenoxolone (100 μM, CBX) did not abolish oscillations (p = 0.46, n = 7, paired t-test; Figures 4B,D). Carbenoxolone alone had a variable effect on the size of oscillations, but they persisted in six out of nine GCs (Figures 5C,D).


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

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

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).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: 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).
Mentions: CNQX and D-AP5 eliminated EPSCs in all rd1 GCs. Oscillatory IPSCs, in contrast, persisted in a large subset of GCs and were abolished after the addition of strychnine (3 μM), gabazine (5 μM) and TPMPA (100 μM), antagonists of glycine-, GABAA-, and GABACRs, respectively (Figure 4A). As evident from FFT heat maps (right panel), oscillations not only persisted, but were refined in a subset of GCs, showing less inter-wave variation in amplitude and frequency, reflected as an increase in power (p = 0.02, n = 11, paired t-test; Figure 4D). Notably, OFF cells all increased in power, while ON cells varied, though most maintained oscillations at reduced power (r2 = 0.67, p < 0.001, n = 26, linear regression; Figure 4C). The persistence of fast aberrant activity in a diversity of GCs suggests that BCs are not the source. An alternate pathway for these oscillations may be gap junction-mediated pathway between BCs and AII cells, which have been suggested to be required for their generation (Borowska et al., 2011) and/or propagation across the retina (Menzler and Zeck, 2011). For rd1 GCs with IPSC oscillations resistant to CNQX and DAP-5, the subsequent addition of the gap junction blocker carbenoxolone (100 μM, CBX) did not abolish oscillations (p = 0.46, n = 7, paired t-test; Figures 4B,D). Carbenoxolone alone had a variable effect on the size of oscillations, but they persisted in six out of nine GCs (Figures 5C,D).

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