Loss of circadian photoentrainment and abnormal retinal electrophysiology in Math5 mutant mice

Joseph A. Brzezinski IV, Nadean L Brown, Atsuhiro Tanikawa, Ronald A. Bush, Paul A. Sieving, Martha H. Vitaterna, Joseph S. Takahashi, Thomas M Glaser

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

PURPOSE. To determine how the absence of retinal ganglion cells (RGCs) in Math5 (Atoh7) mutant mice affects circadian behavior and retinal function. METHODS. The wheel-running behavior of wild-type and Math5 mutant mice was measured under various light-dark cycle conditions. To evaluate retinal input to the suprachiasmatic nuclei (SCN) anatomically, the retinohypothalamic tracts were labeled in vivo. To assess changes in retinal function, corneal flash electroretinograms (ERGs) from mutant and wild-type mice were compared under dark- and light-adapted conditions. Alterations in retinal neuron populations were evaluated quantitatively and with cell-type-specific markers. RESULTS. The Math5-null mice did not entrain to light and exhibited free-running circadian behavior with a mean period (23.6 ± 0.15 hours) that was indistinguishable from that of wild-type mice (23.4 ± 0.19 hours). The SCN showed no anterograde labeling with a horseradish peroxidase-conjugated cholera toxin B (CT-HRP) tracer. ERGs recorded from mutant mice had diminished scotopic a- and b-wave and photopic b-wave amplitudes. The scotopic b-wave was more severely affected than the a-wave. The oscillatory potentials (OPs) and scotopic threshold response (STR) were also reduced. Consistent with these ERG findings, a pan-specific reduction in the number of bipolar cells and a smaller relative decrease in the number of rods in mutant mice were observed. CONCLUSIONS. Math5-null mice are clock-blind and have no RGC projections to the SCN. RGCs are thus essential for photoentrainment in mice, but are not necessary for the development or intrinsic function of the SCN clock. RGCs are not required to generate any of the major ERG waveforms in mice, including the STR, which is produced by ganglion cells in some other species. The diminished amplitude of b-wave, OPs, and STR components in Math5 mutants is most likely caused by the decreased abundance of retinal interneurons.

Original languageEnglish (US)
Pages (from-to)2540-2551
Number of pages12
JournalInvestigative Ophthalmology and Visual Science
Volume46
Issue number7
DOIs
StatePublished - 2005
Externally publishedYes

Fingerprint

Electrophysiology
Suprachiasmatic Nucleus
Retinal Ganglion Cells
Retinal Neurons
Light
Photoperiod
Interneurons
Ganglia
Running
Cell Count

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Loss of circadian photoentrainment and abnormal retinal electrophysiology in Math5 mutant mice. / Brzezinski IV, Joseph A.; Brown, Nadean L; Tanikawa, Atsuhiro; Bush, Ronald A.; Sieving, Paul A.; Vitaterna, Martha H.; Takahashi, Joseph S.; Glaser, Thomas M.

In: Investigative Ophthalmology and Visual Science, Vol. 46, No. 7, 2005, p. 2540-2551.

Research output: Contribution to journalArticle

Brzezinski IV, Joseph A. ; Brown, Nadean L ; Tanikawa, Atsuhiro ; Bush, Ronald A. ; Sieving, Paul A. ; Vitaterna, Martha H. ; Takahashi, Joseph S. ; Glaser, Thomas M. / Loss of circadian photoentrainment and abnormal retinal electrophysiology in Math5 mutant mice. In: Investigative Ophthalmology and Visual Science. 2005 ; Vol. 46, No. 7. pp. 2540-2551.
@article{d448c68c6af24ee895fae89be2e7063e,
title = "Loss of circadian photoentrainment and abnormal retinal electrophysiology in Math5 mutant mice",
abstract = "PURPOSE. To determine how the absence of retinal ganglion cells (RGCs) in Math5 (Atoh7) mutant mice affects circadian behavior and retinal function. METHODS. The wheel-running behavior of wild-type and Math5 mutant mice was measured under various light-dark cycle conditions. To evaluate retinal input to the suprachiasmatic nuclei (SCN) anatomically, the retinohypothalamic tracts were labeled in vivo. To assess changes in retinal function, corneal flash electroretinograms (ERGs) from mutant and wild-type mice were compared under dark- and light-adapted conditions. Alterations in retinal neuron populations were evaluated quantitatively and with cell-type-specific markers. RESULTS. The Math5-null mice did not entrain to light and exhibited free-running circadian behavior with a mean period (23.6 ± 0.15 hours) that was indistinguishable from that of wild-type mice (23.4 ± 0.19 hours). The SCN showed no anterograde labeling with a horseradish peroxidase-conjugated cholera toxin B (CT-HRP) tracer. ERGs recorded from mutant mice had diminished scotopic a- and b-wave and photopic b-wave amplitudes. The scotopic b-wave was more severely affected than the a-wave. The oscillatory potentials (OPs) and scotopic threshold response (STR) were also reduced. Consistent with these ERG findings, a pan-specific reduction in the number of bipolar cells and a smaller relative decrease in the number of rods in mutant mice were observed. CONCLUSIONS. Math5-null mice are clock-blind and have no RGC projections to the SCN. RGCs are thus essential for photoentrainment in mice, but are not necessary for the development or intrinsic function of the SCN clock. RGCs are not required to generate any of the major ERG waveforms in mice, including the STR, which is produced by ganglion cells in some other species. The diminished amplitude of b-wave, OPs, and STR components in Math5 mutants is most likely caused by the decreased abundance of retinal interneurons.",
author = "{Brzezinski IV}, {Joseph A.} and Brown, {Nadean L} and Atsuhiro Tanikawa and Bush, {Ronald A.} and Sieving, {Paul A.} and Vitaterna, {Martha H.} and Takahashi, {Joseph S.} and Glaser, {Thomas M}",
year = "2005",
doi = "10.1167/iovs.04-1123",
language = "English (US)",
volume = "46",
pages = "2540--2551",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "7",

}

TY - JOUR

T1 - Loss of circadian photoentrainment and abnormal retinal electrophysiology in Math5 mutant mice

AU - Brzezinski IV, Joseph A.

AU - Brown, Nadean L

AU - Tanikawa, Atsuhiro

AU - Bush, Ronald A.

AU - Sieving, Paul A.

AU - Vitaterna, Martha H.

AU - Takahashi, Joseph S.

AU - Glaser, Thomas M

PY - 2005

Y1 - 2005

N2 - PURPOSE. To determine how the absence of retinal ganglion cells (RGCs) in Math5 (Atoh7) mutant mice affects circadian behavior and retinal function. METHODS. The wheel-running behavior of wild-type and Math5 mutant mice was measured under various light-dark cycle conditions. To evaluate retinal input to the suprachiasmatic nuclei (SCN) anatomically, the retinohypothalamic tracts were labeled in vivo. To assess changes in retinal function, corneal flash electroretinograms (ERGs) from mutant and wild-type mice were compared under dark- and light-adapted conditions. Alterations in retinal neuron populations were evaluated quantitatively and with cell-type-specific markers. RESULTS. The Math5-null mice did not entrain to light and exhibited free-running circadian behavior with a mean period (23.6 ± 0.15 hours) that was indistinguishable from that of wild-type mice (23.4 ± 0.19 hours). The SCN showed no anterograde labeling with a horseradish peroxidase-conjugated cholera toxin B (CT-HRP) tracer. ERGs recorded from mutant mice had diminished scotopic a- and b-wave and photopic b-wave amplitudes. The scotopic b-wave was more severely affected than the a-wave. The oscillatory potentials (OPs) and scotopic threshold response (STR) were also reduced. Consistent with these ERG findings, a pan-specific reduction in the number of bipolar cells and a smaller relative decrease in the number of rods in mutant mice were observed. CONCLUSIONS. Math5-null mice are clock-blind and have no RGC projections to the SCN. RGCs are thus essential for photoentrainment in mice, but are not necessary for the development or intrinsic function of the SCN clock. RGCs are not required to generate any of the major ERG waveforms in mice, including the STR, which is produced by ganglion cells in some other species. The diminished amplitude of b-wave, OPs, and STR components in Math5 mutants is most likely caused by the decreased abundance of retinal interneurons.

AB - PURPOSE. To determine how the absence of retinal ganglion cells (RGCs) in Math5 (Atoh7) mutant mice affects circadian behavior and retinal function. METHODS. The wheel-running behavior of wild-type and Math5 mutant mice was measured under various light-dark cycle conditions. To evaluate retinal input to the suprachiasmatic nuclei (SCN) anatomically, the retinohypothalamic tracts were labeled in vivo. To assess changes in retinal function, corneal flash electroretinograms (ERGs) from mutant and wild-type mice were compared under dark- and light-adapted conditions. Alterations in retinal neuron populations were evaluated quantitatively and with cell-type-specific markers. RESULTS. The Math5-null mice did not entrain to light and exhibited free-running circadian behavior with a mean period (23.6 ± 0.15 hours) that was indistinguishable from that of wild-type mice (23.4 ± 0.19 hours). The SCN showed no anterograde labeling with a horseradish peroxidase-conjugated cholera toxin B (CT-HRP) tracer. ERGs recorded from mutant mice had diminished scotopic a- and b-wave and photopic b-wave amplitudes. The scotopic b-wave was more severely affected than the a-wave. The oscillatory potentials (OPs) and scotopic threshold response (STR) were also reduced. Consistent with these ERG findings, a pan-specific reduction in the number of bipolar cells and a smaller relative decrease in the number of rods in mutant mice were observed. CONCLUSIONS. Math5-null mice are clock-blind and have no RGC projections to the SCN. RGCs are thus essential for photoentrainment in mice, but are not necessary for the development or intrinsic function of the SCN clock. RGCs are not required to generate any of the major ERG waveforms in mice, including the STR, which is produced by ganglion cells in some other species. The diminished amplitude of b-wave, OPs, and STR components in Math5 mutants is most likely caused by the decreased abundance of retinal interneurons.

UR - http://www.scopus.com/inward/record.url?scp=23244466329&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23244466329&partnerID=8YFLogxK

U2 - 10.1167/iovs.04-1123

DO - 10.1167/iovs.04-1123

M3 - Article

C2 - 15980246

AN - SCOPUS:23244466329

VL - 46

SP - 2540

EP - 2551

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 7

ER -