Melanopsin-expressing and intrinsically photosensitive retinal ganglion cells (mRGC or ipRGC) are indispensable for non-image forming (NIF) visual responses including pupillary light reflex, photoentrainment of the circadian clock, brightness perception in image-forming vision, light modulation of -activity, -sleep, and - pineal melatonin synthesis. Despite these pleiotropic roles of mRGCs, a comprehensive map of their central projections, genetically defined cell types that receive mRGC input, and synaptic ultra-structure are incomplete. This application will make innovative use of mouse genetics and viral vectors to specifically express fluorescent and electron microscopy reporter miniSOG in the mRGCs of mouse retina. Inherent fluorescence of miniSOG will guide selection of mRGC subtypes for subsequent analyses by serial blockface electron microscopy (SBEM). Automatic segmentation of miniSOG labeled neurites and soma will accelerate rapid 3D reconstruction of different subtypes of mRGCs, which will be used as scaffolds to reconstruct a comprehensive intra-retinal connectivity map of mRGCs. Using engineered rabies virus for monosynaptic retrograde transmission, mRGC cell types and their pre-synaptic retinal neurons constituting light input circuits to different target brain regions will be mapped. The mRGC connectivity in the target brain regions will be further mapped at ultrastructure level by combining electron microscopy reporter miniSOG and SBEM. All together the application will generate cellular networks of mRGC subtypes, identify cell types that receive mRGC inputs in the brain, and establish tools and techniques that can be used to unravel the connectivity of any genetically defined neuron.

Public Health Relevance

Specialized groups of light sensitive neurons in the retina play an indispensable role in adapting our activity, sleep, and hormone levels to the ambient light-dark cycle. This application will elucidate the cellular circuitry by which these light sensitive neurons exert their effect on broad brain regions.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY016807-12
Application #
9663942
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Greenwell, Thomas
Project Start
2007-05-01
Project End
2020-03-31
Budget Start
2019-04-01
Budget End
2020-03-31
Support Year
12
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
078731668
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Manoogian, Emily N C; Panda, Satchidananda (2017) Circadian rhythms, time-restricted feeding, and healthy aging. Ageing Res Rev 39:59-67
Longo, Valter D; Panda, Satchidananda (2016) Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan. Cell Metab 23:1048-1059
Manoogian, Emily N C; Panda, Satchidananda (2016) Circadian clock, nutrient quality, and eating pattern tune diurnal rhythms in the mitochondrial proteome. Proc Natl Acad Sci U S A 113:3127-9
Chaix, Amandine; Zarrinpar, Amir; Panda, Satchidananda (2016) The circadian coordination of cell biology. J Cell Biol 215:15-25
Chaix, Amandine; Panda, Satchidananda (2016) Ketone Bodies Signal Opportunistic Food-Seeking Activity. Trends Endocrinol Metab 27:350-352
Panda, Satchidananda (2016) Circadian physiology of metabolism. Science 354:1008-1015
Mure, Ludovic S; Hatori, Megumi; Zhu, Quansheng et al. (2016) Melanopsin-Encoded Response Properties of Intrinsically Photosensitive Retinal Ganglion Cells. Neuron 90:1016-27
Gill, Shubhroz; Le, Hiep D; Melkani, Girish C et al. (2015) Time-restricted feeding attenuates age-related cardiac decline in Drosophila. Science 347:1265-9
Gill, Shubhroz; Panda, Satchidananda (2015) A Smartphone App Reveals Erratic Diurnal Eating Patterns in Humans that Can Be Modulated for Health Benefits. Cell Metab 22:789-98
Chaix, Amandine; Zarrinpar, Amir; Miu, Phuong et al. (2014) Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges. Cell Metab 20:991-1005

Showing the most recent 10 out of 30 publications