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Whole-Retina Reduced Electrophysiological Activity in Mice Bearing Retina-Specific Deletion of Vesicular Acetylcholine Transporter.

Bedore J, Martyn AC, Li AK, Dolinar EA, McDonald IS, Coupland SG, Prado VF, Prado MA, Hill KA - PLoS ONE (2015)

Bottom Line: One of the unanswered questions is how acetylcholine contributes to the functional capacity of mature retinal circuits.Reduced a-wave amplitude was proportional to the reduction in b-wave amplitude and not associated with altered a-wave 10%-90% rise time or inner and outer segment thicknesses.Reduced amplitude across the electroretinogram wave form does not suggest dysfunction in specific retinal cell types and could reflect underlying changes in the retinal and/or extraretinal microenvironment.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, The University of Western Ontario, London, Ontario, Canada N6A 5B7.

ABSTRACT

Background: Despite rigorous characterization of the role of acetylcholine in retinal development, long-term effects of its absence as a neurotransmitter are unknown. One of the unanswered questions is how acetylcholine contributes to the functional capacity of mature retinal circuits. The current study investigates the effects of disrupting cholinergic signalling in mice, through deletion of vesicular acetylcholine transporter (VAChT) in the developing retina, pigmented epithelium, optic nerve and optic stalk, on electrophysiology and structure of the mature retina.

Methods & results: A combination of electroretinography, optical coherence tomography imaging and histological evaluation assessed retinal integrity in mice bearing retina- targeted (embryonic day 12.5) deletion of VAChT (VAChTSix3-Cre-flox/flox) and littermate controls at 5 and 12 months of age. VAChTSix3-Cre-flox/flox mice did not show any gross changes in nuclear layer cellularity or synaptic layer thickness. However, VAChTSix3-Cre-flox/flox mice showed reduced electrophysiological response of the retina to light stimulus under scotopic conditions at 5 and 12 months of age, including reduced a-wave, b-wave, and oscillatory potential (OP) amplitudes and decreased OP peak power and total energy. Reduced a-wave amplitude was proportional to the reduction in b-wave amplitude and not associated with altered a-wave 10%-90% rise time or inner and outer segment thicknesses.

Significance: This study used a novel genetic model in the first examination of function and structure of the mature mouse retina with disruption of cholinergic signalling. Reduced amplitude across the electroretinogram wave form does not suggest dysfunction in specific retinal cell types and could reflect underlying changes in the retinal and/or extraretinal microenvironment. Our findings suggest that release of acetylcholine by VAChT is essential for the normal electrophysiological response of the mature mouse retina.

No MeSH data available.


Related in: MedlinePlus

Quantitative assessment of rod sensitivity.The 10%-90% rise time of the leading edge of the a-wave measured for the top three luminances was similar between VAChTSix3-Cre-flox/flox (open circles) and littermate controls (VAChTflox/flox, closed squares) at (A) 5 (n = 7 VAChTSix3-Cre-flox/flox and n = 13 littermate control) and (B) 12 months of age (n = 3 VAChTSix3-Cre-flox/flox and n = 5 littermate control). The 10%-90% rise time was unaffected by the absence of VAChT at either age examined. Values represent the mean ± SEM.
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pone.0133989.g005: Quantitative assessment of rod sensitivity.The 10%-90% rise time of the leading edge of the a-wave measured for the top three luminances was similar between VAChTSix3-Cre-flox/flox (open circles) and littermate controls (VAChTflox/flox, closed squares) at (A) 5 (n = 7 VAChTSix3-Cre-flox/flox and n = 13 littermate control) and (B) 12 months of age (n = 3 VAChTSix3-Cre-flox/flox and n = 5 littermate control). The 10%-90% rise time was unaffected by the absence of VAChT at either age examined. Values represent the mean ± SEM.

Mentions: Specific analysis of rod sensitivity through measurement of the 10% to 90% rise time of the a-wave found no significant differences between VAChTSix3-Cre-flox/flox and littermate controls in 10%-90% rise time at either 5 or 12 months of age (Fig 5). Even at the highest luminance, the 10% to 90% rise time of the a-wave was not different between genotypes. In littermate controls, the shorter 10% to 90% rise time response was as expected for increased luminance (Fig 5). There was no significant difference in the 10% to 90% rise time response with age in littermate control mice.


Whole-Retina Reduced Electrophysiological Activity in Mice Bearing Retina-Specific Deletion of Vesicular Acetylcholine Transporter.

Bedore J, Martyn AC, Li AK, Dolinar EA, McDonald IS, Coupland SG, Prado VF, Prado MA, Hill KA - PLoS ONE (2015)

Quantitative assessment of rod sensitivity.The 10%-90% rise time of the leading edge of the a-wave measured for the top three luminances was similar between VAChTSix3-Cre-flox/flox (open circles) and littermate controls (VAChTflox/flox, closed squares) at (A) 5 (n = 7 VAChTSix3-Cre-flox/flox and n = 13 littermate control) and (B) 12 months of age (n = 3 VAChTSix3-Cre-flox/flox and n = 5 littermate control). The 10%-90% rise time was unaffected by the absence of VAChT at either age examined. Values represent the mean ± SEM.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4520552&req=5

pone.0133989.g005: Quantitative assessment of rod sensitivity.The 10%-90% rise time of the leading edge of the a-wave measured for the top three luminances was similar between VAChTSix3-Cre-flox/flox (open circles) and littermate controls (VAChTflox/flox, closed squares) at (A) 5 (n = 7 VAChTSix3-Cre-flox/flox and n = 13 littermate control) and (B) 12 months of age (n = 3 VAChTSix3-Cre-flox/flox and n = 5 littermate control). The 10%-90% rise time was unaffected by the absence of VAChT at either age examined. Values represent the mean ± SEM.
Mentions: Specific analysis of rod sensitivity through measurement of the 10% to 90% rise time of the a-wave found no significant differences between VAChTSix3-Cre-flox/flox and littermate controls in 10%-90% rise time at either 5 or 12 months of age (Fig 5). Even at the highest luminance, the 10% to 90% rise time of the a-wave was not different between genotypes. In littermate controls, the shorter 10% to 90% rise time response was as expected for increased luminance (Fig 5). There was no significant difference in the 10% to 90% rise time response with age in littermate control mice.

Bottom Line: One of the unanswered questions is how acetylcholine contributes to the functional capacity of mature retinal circuits.Reduced a-wave amplitude was proportional to the reduction in b-wave amplitude and not associated with altered a-wave 10%-90% rise time or inner and outer segment thicknesses.Reduced amplitude across the electroretinogram wave form does not suggest dysfunction in specific retinal cell types and could reflect underlying changes in the retinal and/or extraretinal microenvironment.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, The University of Western Ontario, London, Ontario, Canada N6A 5B7.

ABSTRACT

Background: Despite rigorous characterization of the role of acetylcholine in retinal development, long-term effects of its absence as a neurotransmitter are unknown. One of the unanswered questions is how acetylcholine contributes to the functional capacity of mature retinal circuits. The current study investigates the effects of disrupting cholinergic signalling in mice, through deletion of vesicular acetylcholine transporter (VAChT) in the developing retina, pigmented epithelium, optic nerve and optic stalk, on electrophysiology and structure of the mature retina.

Methods & results: A combination of electroretinography, optical coherence tomography imaging and histological evaluation assessed retinal integrity in mice bearing retina- targeted (embryonic day 12.5) deletion of VAChT (VAChTSix3-Cre-flox/flox) and littermate controls at 5 and 12 months of age. VAChTSix3-Cre-flox/flox mice did not show any gross changes in nuclear layer cellularity or synaptic layer thickness. However, VAChTSix3-Cre-flox/flox mice showed reduced electrophysiological response of the retina to light stimulus under scotopic conditions at 5 and 12 months of age, including reduced a-wave, b-wave, and oscillatory potential (OP) amplitudes and decreased OP peak power and total energy. Reduced a-wave amplitude was proportional to the reduction in b-wave amplitude and not associated with altered a-wave 10%-90% rise time or inner and outer segment thicknesses.

Significance: This study used a novel genetic model in the first examination of function and structure of the mature mouse retina with disruption of cholinergic signalling. Reduced amplitude across the electroretinogram wave form does not suggest dysfunction in specific retinal cell types and could reflect underlying changes in the retinal and/or extraretinal microenvironment. Our findings suggest that release of acetylcholine by VAChT is essential for the normal electrophysiological response of the mature mouse retina.

No MeSH data available.


Related in: MedlinePlus