The Scotopic Threshold Response of the Dark‐Adapted Electroretinogram of the Mouse

The most sensitive response in the dark‐adapted electroretinogram (ERG), the scotopic threshold response (STR) which originates from the proximal retina, has been identified in several mammals including humans, but previously not in the mouse. The current study established the presence and assessed the nature of the mouse STR. ERGs were recorded from adult wild‐type C57/BL6 mice anaesthetized with ketamine (70 mg kg−1) and xylazine (7 mg kg−1). Recordings were between DTL fibres placed under contact lenses on the two eyes. Monocular test stimuli were brief flashes (λmax 462 nm; ‐6.1 to +1.8 log scotopic Troland seconds(sc td s)) under fully dark‐adapted conditions and in the presence of steady adapting backgrounds (‐3.2 to ‐1.7 log sc td). For the weakest test stimuli, ERGs consisted of a slow negative potential maximal ≈200 ms after the flash, with a small positive potential preceding it. The negative wave resembled the STR of other species. As intensity was increased, the negative potential saturated but the positive potential (maximal ≈110 ms) continued to grow as the b‐wave. For stimuli that saturated the b‐wave, the a‐wave emerged. For stimulus strengths up to those at which the a‐wave emerged, ERG amplitudes measured at fixed times after the flash (110 and 200 ms) were fitted with a model assuming an initially linear rise of response amplitude with intensity, followed by saturation of five components of declining sensitivity: a negative STR (nSTR), a positive STR (pSTR), a positive scotopic response (pSR), PII (the bipolar cell component) and PIII (the photoreceptor component). The nSTR and pSTR were approximately 3 times more sensitive than the pSR, which was approximately 7 times more sensitive than PII. The sensitive positive components dominated the b‐wave up to > 5 % of its saturated amplitude. Pharmacological agents that suppress proximal retinal activity (e.g. GABA) minimized the pSTR, nSTR and pSR, essentially isolating PII which rose linearly with intensity before showing hyperbolic saturation. The nSTR, pSTR and pSR were desensitized by weaker backgrounds than those desensitizing PII. In conclusion, ERG components of proximal retinal origin that are more sensitive to test flashes and adapting backgrounds than PII provide the ‘threshold’ negative and positive (b‐wave) responses of the mouse dark‐adapted ERG. These results support the use of the mouse ERG in studies of proximal retinal function.

[1]  J. Robson,et al.  Dissecting the dark-adapted electroretinogram , 1998, Documenta Ophthalmologica.

[2]  Bert Sakmann,et al.  Scotopic and mesopic light adaptation in the cat's retina , 1969, Pflügers Archiv.

[3]  L. Frishman,et al.  Response Properties of Rod Photoreceptors in Nob Mice Determined by Paired-flash Electroretinography , 2002 .

[4]  F. Rieke,et al.  Nonlinear Signal Transfer from Mouse Rods to Bipolar Cells and Implications for Visual Sensitivity , 2002, Neuron.

[5]  P. Lukasiewicz,et al.  Elimination of the ρ1 Subunit Abolishes GABACReceptor Expression and Alters Visual Processing in the Mouse Retina , 2002, The Journal of Neuroscience.

[6]  Heinz Wässle,et al.  Vesicular γ‐aminobutyric acid transporter expression in amacrine and horizontal cells , 2002 .

[7]  H. Wässle,et al.  Vesicular gamma-aminobutyric acid transporter expression in amacrine and horizontal cells. , 2002, The Journal of comparative neurology.

[8]  P. Sterling,et al.  Microcircuits for Night Vision in Mouse Retina , 2001, The Journal of Neuroscience.

[9]  R. Weiler,et al.  Visual Transmission Deficits in Mice with Targeted Disruption of the Gap Junction Gene Connexin36 , 2001, The Journal of Neuroscience.

[10]  F. Naarendorp,et al.  Absolute and relative sensitivity of the scotopic system of rat: Electroretinography and behavior , 2001, Visual Neuroscience.

[11]  H. Wässle,et al.  Morphological and physiological properties of the A17 amacrine cell of the rat retina , 2000, Visual Neuroscience.

[12]  H. Wässle,et al.  Immunocytochemical analysis of the mouse retina , 2000, The Journal of comparative neurology.

[13]  A. Berntson,et al.  Response characteristics and receptive field widths of on‐bipolar cells in the mouse retina , 2000, The Journal of physiology.

[14]  D Malakoff,et al.  The Rise of the Mouse, Biomedicine's Model Mammal , 2000, Science.

[15]  R H Masland,et al.  Light-evoked responses of bipolar cells in a mammalian retina. , 2000, Journal of neurophysiology.

[16]  S. Bloomfield,et al.  Surround inhibition of mammalian AII amacrine cells is generated in the proximal retina , 2000, The Journal of physiology.

[17]  D. G. Green,et al.  A dissection of the electroretinogram from the isolated rat retina with microelectrodes and drugs , 1999, Visual Neuroscience.

[18]  G. Falk,et al.  Contribution of rod, on-bipolar, and horizontal cell light responses to the ERG of dogfish retina , 1999, Visual Neuroscience.

[19]  Earl L. Smith,et al.  The photopic negative response of the macaque electroretinogram: reduction by experimental glaucoma. , 1999, Investigative ophthalmology & visual science.

[20]  J. Hetling,et al.  Sensitivity and kinetics of mouse rod flash responses determined in vivo from paired‐flash electroretinograms , 1999, The Journal of physiology.

[21]  P. Sieving,et al.  The electroretinogram of the rhodopsin knockout mouse , 1999, Visual Neuroscience.

[22]  E. Pugh,et al.  UV- and Midwave-Sensitive Cone-Driven Retinal Responses of the Mouse: A Possible Phenotype for Coexpression of Cone Photopigments , 1999, The Journal of Neuroscience.

[23]  J. Robson,et al.  Inner retinal signal processing: adaptation to environmental light , 1999 .

[24]  R. Masland,et al.  The Major Cell Populations of the Mouse Retina , 1998, The Journal of Neuroscience.

[25]  E. Pugh,et al.  The Origin of the Major Rod- and Cone-Driven Components of the Rodent Electroretinogram and the Effect of Age and Light-Rearing History on the Magnitude of These Components , 1998 .

[26]  J. Robson,et al.  Effects of background light on the human dark-adapted electroretinogram and psychophysical threshold. , 1996, Journal of the Optical Society of America. A, Optics, image science, and vision.

[27]  E. Pugh,et al.  Recovery phase of the murine rod photoresponse reconstructed from electroretinographic recordings , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[28]  R S Harwerth,et al.  The scotopic electroretinogram of macaque after retinal ganglion cell loss from experimental glaucoma. , 1996, Investigative ophthalmology & visual science.

[29]  J. Robson,et al.  Response linearity and kinetics of the cat retina: The bipolar cell component of the dark-adapted electroretinogram , 1995, Visual Neuroscience.

[30]  R. Hansen,et al.  The VEP thresholds for full-field stimuli in dark-adapted infants , 1995, Visual Neuroscience.

[31]  P. Sieving,et al.  Evidence for two sites of adaptation affecting the dark-adapted ERG of cats and primates , 1995, Vision Research.

[32]  D. G. Green,et al.  Behavioral estimates of absolute threshold in rat , 1994, Visual Neuroscience.

[33]  D. G. Green,et al.  Electrophysiological estimates of visual sensitivity in albino and pigmented mice , 1994, Visual Neuroscience.

[34]  C. Karwoski,et al.  Current source density analysis of retinal field potentials. II. Pharmacological analysis of the b-wave and M-wave. , 1994, Journal of neurophysiology.

[35]  J. Hayes,et al.  Elevated dark-adapted thresholds in hypopigmented mice measured with a water maze screening apparatus , 1993, Behavior genetics.

[36]  C. Remé,et al.  Chronic lithium treatment induces reversible and irreversible changes in the rat ERG in vivo , 1992 .

[37]  P. Sieving,et al.  The scotopic threshold response of the cat erg is suppressed selectively by GABA and glycine , 1991, Vision Research.

[38]  P. Sieving Retinal ganglion cell loss does not abolish the scotopic threshold response (STR) of the cat and human ERG , 1991 .

[39]  P. Sieving,et al.  Comparison of rod threshold erg from monkey, cat and human , 1991 .

[40]  L. Frishman,et al.  Intraretinal analysis of the threshold dark-adapted ERG of cat retina. , 1989, Journal of neurophysiology.

[41]  L. Frishman,et al.  Light-evoked increases in [K+]o in proximal portion of the dark-adapted cat retina. , 1989, Journal of neurophysiology.

[42]  M. Slaughter,et al.  B-wave of the electroretinogram. A reflection of ON bipolar cell activity , 1989, The Journal of general physiology.

[43]  P. Sieving,et al.  Scotopic threshold response (STR) of the human electroretinogram. , 1988, Investigative ophthalmology & visual science.

[44]  P Sterling,et al.  Microcircuitry of the dark-adapted cat retina: functional architecture of the rod-cone network , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[45]  L. Frishman,et al.  Scotopic threshold response of proximal retina in cat. , 1986, Journal of neurophysiology.

[46]  D. Baylor,et al.  The photocurrent, noise and spectral sensitivity of rods of the monkey Macaca fascicularis. , 1984, The Journal of physiology.

[47]  Maureen K. Powers,et al.  Mechanisms of light adaptation in rat retina , 1982, Vision Research.

[48]  M. Lavail,et al.  Rods and cones in the mouse retina. I. Structural analysis using light and electron microscopy , 1979, The Journal of comparative neurology.

[49]  G. Trick,et al.  Improved electrode for electroretinography. , 1979, Investigative ophthalmology & visual science.

[50]  Anne B. Fulton,et al.  The human rod ERG: Correlation with psychophysical responses in light and dark adaptation , 1978, Vision Research.

[51]  H. Barlow,et al.  Responses to single quanta of light in retinal ganglion cells of the cat. , 1971, Vision research.

[52]  J. Dowling,et al.  Intracellular responses of the Müller (glial) cells of mudpuppy retina: their relation to b-wave of the electroretinogram. , 1970, Journal of neurophysiology.

[53]  W. A. Hagins,et al.  Signal Transmission along Retinal Rods and the Origin of the Electroretinographic a-Wave , 1969, Nature.

[54]  Gunther Wyszecki,et al.  Color Science: Concepts and Methods, Quantitative Data and Formulae, 2nd Edition , 2000 .

[55]  R. Cone Quantum Relations of the Rat Electroretinogram , 1963, The Journal of general physiology.

[56]  H B BARLOW,et al.  Increment thresholds at low intensities considered as signal/noise discriminations , 1957, The Journal of physiology.

[57]  H. Barlow Retinal noise and absolute threshold. , 1956, Journal of the Optical Society of America.

[58]  R. Granit The components of the retinal action potential in mammals and their relation to the discharge in the optic nerve , 1933, The Journal of physiology.