title: Whole-Retina Reduced Electrophysiological Activity in Mice Bearing Retina-Specific Deletion of Vesicular Acetylcholine Transporter.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biology, The University of Western Ontario, London, Ontario, Canada N6A 5B7.
authors.forename: Jake
authors.initials: J
authors.lastname: Bedore
authors.affiliation: Molecular Medicine, Robarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada N6A 5B7.
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Martyn
authors.affiliation: Department of Biology, The University of Western Ontario, London, Ontario, Canada N6A 5B7.
authors.forename: Anson K C
authors.initials: AK
authors.lastname: Li
authors.affiliation: Department of Biology, The University of Western Ontario, London, Ontario, Canada N6A 5B7.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Dolinar
authors.affiliation: Department of Biology, The University of Western Ontario, London, Ontario, Canada N6A 5B7.
authors.forename: Ian S
authors.initials: IS
authors.lastname: McDonald
authors.affiliation: Ophthalmology, Cellular and Molecular Medicine, University of Ottawa, Ottawa Eye Institute, Ottawa, Ontario, Canada K1H 8L6.
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Coupland
authors.affiliation: Molecular Medicine, Robarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada N6A 5B7.
authors.forename: Vania F
authors.initials: VF
authors.lastname: Prado
authors.affiliation: Molecular Medicine, Robarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada N6A 5B7.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Prado
authors.affiliation: Department of Biology, The University of Western Ontario, London, Ontario, Canada N6A 5B7.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Hill
mesh_terms: D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D004596:Electroretinography; D017353:Gene Deletion; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018377:Neurotransmitter Agents / Q000502:physiology*; D009900:Optic Nerve / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000502:physiology*; D055213:Retinal Pigment Epithelium / Q000502:physiology; D041623:Tomography, Optical Coherence; D050494:Vesicular Acetylcholine Transport Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D018377:Neurotransmitter Agents; C493460:Slc18a3 protein, mouse; D050494:Vesicular Acetylcholine Transport Proteins; D000109:Acetylcholine