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Originally published In Press as doi:10.1167/iovs.08-1936 on June 6, 2008
(Investigative Ophthalmology and Visual Science. 2008;49:4655-4663.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.08-1936

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Evaluating Neural Activity of Retinal Ganglion Cells by Flash-Evoked Intrinsic Signal Imaging in Macaque Retina

Gen Hanazono,1,2,3 Kazushige Tsunoda,1,2 Yoko Kazato,1,2,4 Kazuo Tsubota,5 and Manabu Tanifuji2

1From the Laboratory of Visual Physiology, National Institute of Sensory Organs, Tokyo, Japan; 2Laboratory for Integrative Neural Systems, Brain Science Institute, RIKEN, Saitama, Japan; 3Department of Ophthalmology, Kikkoman General Hospital, Chiba, Japan; 4Department of Ophthalmology, Nihon University School of Medicine, Tokyo, Japan; and 5Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.

PURPOSE. Intrinsic signal imaging (ISI) detects light-induced microstructural or metabolic changes in retinal tissues. Thus, activities of the rod and cone systems could be mapped topographically. However, no direct evidence indicates the cellular origin of the signals. The purpose of this study was to determine whether and how retinal ganglion cells (RGCs) contribute to ISI.

METHODS. In anesthetized macaque monkeys, the properties of intrinsic signals were investigated by simultaneous measurement of the retina and the primary visual cortex (V1) with different wavelengths of observation light, measurement of the flash-induced blood flow changes by laser Doppler flowmetry, and intravitreal injection of tetrodotoxin (TTX).

RESULTS. Slow components of ISI correspond well to the flash-induced blood flow increase. Intrinsic signals of the posterior retina are partially decreased, and the signal of the optic disc is completely abolished by intravitreal injection of TTX at a concentration that should reduce the neural activities of RGCs. The intrinsic signal at the fovea did not change significantly after TTX injection.

CONCLUSIONS. Photoreceptors in the outer retina and RGCs in the inner retina are major contributors to the intrinsic signals, and the activity of the RGCs can be mapped by using fast and slow components of the signal in the posterior retina. The functional organization of the RGC layer has not been objectively mapped; results presented here indicate that the ISI has the potential to do this.








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