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Related Research Units

Intellectual and Developmental Disabilities Research Center Research
Neurology Research
Do Laboratory Research
F.M. Kirby Neurobiology Center

Research Overview

Our lab asks how light drives functions that are as diverse as visual perception, sleep regulation, hormonal control, and setting of the internal body clock. We pose this question for species that occupy distinct ecological niches to learn how visual mechanisms are tailored to different behavioral needs. Our research spans organizational levels and time scales, from molecules to circuits and from milliseconds to hours. It centers on electrophysiological and optical techniques that are applied in vitro and in vivo.

Visual performance is remarkable. Perception can be elicited by a handful of photons, yet continues when the light level has intensified by many orders of magnitude. How is this dynamic range established? In cases of severe blindness where visual awareness is lost, light can still keep the body clock and hormone levels in register with the solar cycle. What are the origins of this robustness?

Questions of dynamic range, robustness, and other parameters of system operation recur throughout the biological sciences. We pose them in the visual system, where the input (light) can be precisely controlled and its effects can be quantified at levels ranging from the conformational changes of molecules to alterations in behavior. We seek connections between these levels.

We focus on two aspects of the visual system. The first is the fovea, a retinal specialization that initiates most visual perception in humans and other primates but is found in no other mammal. We seek to understand how the fovea supports the exceptional visual acuity of primates, which is 10-fold higher than that of cats and 100-fold higher than that of mice. The second concerns unusual photoreceptors; these are not the classical rods and cones, but a population of retinal output neurons that capture light with a molecule called melanopsin. Signals from these intrinsically photosensitive retinal ganglion cells (ipRGCs) largely bypass consciousness while exerting a broad influence on physiology. We study the mechanisms of signal generation by ipRGCs and interpret them in the context of downstream circuits in the retina and brain.

An understanding of the visual system provides the foundation for maintaining its health, detecting disease, and developing methods to forestall and reverse blindness.

Research Background

Michael Tri H. Do is a member of the F.M. Kirby Neurobiology Center at Boston Children's Hospital and an Assistant Professor of Neurology at Harvard Medical School. His postdoctoral work, done with King-Wai Yau at the Johns Hopkins University School of Medicine, concerned an unusual type of mammalian photoreceptor that sends information directly from the retina to the brain. He completed his Ph.D. with Bruce Bean at Harvard Medical School, investigating the origin of electrical activity in certain cells of the basal ganglia. As an undergraduate at Georgetown University, he worked with Susette Mueller to learn how some types of cancer cells grow and spread more effectively than others.

 

Publications

  1. Molecular and spatial analysis of ganglion cells on retinal flatmounts: diversity, topography, and perivascularity. bioRxiv. 2024 Dec 17. View Abstract
  2. Pupil constriction by contrast for contrast. Neuron. 2024 Jul 17; 112(14):2261-2262. View Abstract
  3. New-Onset Hypertension and Seizures in a 10-year-old Girl with Cyclic Vomiting Syndrome. Pediatr Rev. 2024 Apr 01; 45(4):230-233. View Abstract
  4. Recommendations for measuring and standardizing light for laboratory mammals to improve welfare and reproducibility in animal research. PLoS Biol. 2024 Mar; 22(3):e3002535. View Abstract
  5. The Multistable Melanopsins of Mammals. Front Ophthalmol (Lausanne). 2023; 3. View Abstract
  6. Encoding of environmental illumination by primate melanopsin neurons. Science. 2023 01 27; 379(6630):376-381. View Abstract
  7. Light links neonatal neurons for learning. Cell. 2022 08 18; 185(17):3081-3083. View Abstract
  8. Individual variations of visual information. Neuron. 2022 02 16; 110(4):564-565. View Abstract
  9. Retinal ganglion cells expressing CaM kinase II in human and nonhuman primates. J Comp Neurol. 2022 06; 530(9):1470-1493. View Abstract
  10. Satb1 expression in retinal ganglion cells of marmosets, macaques, and humans. J Comp Neurol. 2022 04; 530(6):923-940. View Abstract
  11. Optimized Signal Flow through Photoreceptors Supports the High-Acuity Vision of Primates. Neuron. 2020 10 28; 108(2):335-348.e7. View Abstract
  12. Melanopsin and the Intrinsically Photosensitive Retinal Ganglion Cells: Biophysics to Behavior. Neuron. 2019 10 23; 104(2):205-226. View Abstract
  13. Molecular Classification and Comparative Taxonomics of Foveal and Peripheral Cells in Primate Retina. Cell. 2019 02 21; 176(5):1222-1237.e22. View Abstract
  14. Mixed Palettes of Melanopsin Phototransduction. Cell. 2018 10 18; 175(3):637-639. View Abstract
  15. Biophysical Variation within the M1 Type of Ganglion Cell Photoreceptor. Cell Rep. 2017 Oct 24; 21(4):1048-1062. View Abstract
  16. A Population Representation of Absolute Light Intensity in the Mammalian Retina. Cell. 2017 Nov 02; 171(4):865-876.e16. View Abstract
  17. The outer and inner halves of photoreceptor adaptation. J Physiol. 2017 06 01; 595(11):3247-3248. View Abstract
  18. Melanopsin tristability for sustained and broadband phototransduction. Neuron. 2015 Mar 04; 85(5):1043-55. View Abstract
  19. Adaptation to steady light by intrinsically photosensitive retinal ganglion cells. Proc Natl Acad Sci U S A. 2013 Apr 30; 110(18):7470-5. View Abstract
  20. Melanopsin-positive intrinsically photosensitive retinal ganglion cells: from form to function. J Neurosci. 2011 Nov 09; 31(45):16094-101. View Abstract
  21. Melanopsin signalling in mammalian iris and retina. Nature. 2011 Nov 02; 479(7371):67-73. View Abstract
  22. Tracer coupling of intrinsically photosensitive retinal ganglion cells to amacrine cells in the mouse retina. J Comp Neurol. 2010 Dec 01; 518(23):4813-24. View Abstract
  23. Intrinsically photosensitive retinal ganglion cells. Physiol Rev. 2010 Oct; 90(4):1547-81. View Abstract
  24. Photon capture and signalling by melanopsin retinal ganglion cells. Nature. 2009 Jan 15; 457(7227):281-7. View Abstract
  25. Non-image-forming ocular photoreception in vertebrates. Curr Opin Neurobiol. 2005 Aug; 15(4):415-22. View Abstract
  26. Sodium currents in subthalamic nucleus neurons from Nav1.6-null mice. J Neurophysiol. 2004 Aug; 92(2):726-33. View Abstract
  27. Subthreshold sodium currents and pacemaking of subthalamic neurons: modulation by slow inactivation. Neuron. 2003 Jul 03; 39(1):109-20. View Abstract
  28. The Syk tyrosine kinase suppresses malignant growth of human breast cancer cells. Nature. 2000 Aug 17; 406(6797):742-7. View Abstract
  29. Phagocytosis of cross-linked gelatin matrix by human breast carcinoma cells correlates with their invasive capacity. Clin Cancer Res. 1998 Feb; 4(2):507-15. View Abstract

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