Alapakkam P Sampath

Department Vice Chair, Ophthalmology, University of California Los Angeles

Professor, Ophthalmology, University of California Los Angeles

Professor, Neurobiology, University of California Los Angeles

UC Profile

I hold the Grace and Walter Lantz Endowed Chair in Ophthalmology. My research interests have centered on the physiological function of retinal photoreceptor cells, the rods and cones. In particular, I have studied mechanisms of phototransduction activation and regulation, and how the photoreceptor cell output is represented in the retinal circuitry. Since 2005, the major research focus of my independent laboratory has been in using transgenic mice that display perturbations in photoreceptor function, or retinal connectivity, to establish how rod and cone photoreceptors relay light-evoked signals to bipolar cells over a wide range of light intensities. Much of this work has focused on how single-photon responses are transmitted across the retinal circuitry under conditions where few of the rods are generating them. However, more recently the laboratory has endeavored to establish the mechanisms by which both rod and cone photoreceptors function over a wide range of light intensities, and how retinal function is compromised following retinal degeneration.

Education and Training

University of WashingtonSr Fellow12/2004Physiology & Biophysics
Stanford UniversityPostdoc12/2001Neurobiology
University of CaliforniaPhD05/1999Physiological Science
University of CaliforniaAB05/1994Molecular and Cell Biology

Publications

  1. Chung DD, Chen AC, Choo CH, Zhang W, Williams D, Griffis CG, Bonezzi P, Jatavallabhula K, Sampath AP, Aldave AJ. Investigation of the functional impact of CHED- and FECD4-associated SLC4A11 mutations in human corneal endothelial cells.. PloS one, 2024.
  2. Scalabrino ML, Thapa M, Wang T, Sampath AP, Chen J, Field GD. Late gene therapy limits the restoration of retinal function in a mouse model of retinitis pigmentosa.. Nature communications, 2023.
  3. Griffis KG, Fehlhaber KE, Rieke F, Sampath AP. Light Adaptation of Retinal Rod Bipolar Cells.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2023.
  4. Fehlhaber KE, Majumder A, Boyd KK, Griffis KG, Artemyev NO, Fain GL, Sampath AP. A Novel Role for UNC119 as an Enhancer of Synaptic Transmission.. International journal of molecular sciences, 2023.
  5. Scalabrino ML, Thapa M, Wang T, Sampath AP, Chen J, Field GD. Late gene therapy limits the restoration of retinal function in a mouse model of retinitis pigmentosa.. bioRxiv : the preprint server for biology, 2023.
  6. Ellis EM, Paniagua AE, Scalabrino ML, Thapa M, Rathinavelu J, Jiao Y, Williams DS, Field GD, Fain GL, Sampath AP. Cones and cone pathways remain functional in advanced retinal degeneration.. Current biology : CB, 2023.
  7. Scalabrino ML, Thapa M, Chew LA, Zhang E, Xu J, Sampath AP, Chen J, Field GD. Robust cone-mediated signaling persists late into rod photoreceptor degeneration.. eLife, 2022.
  8. Frederiksen R, Fain GL, Sampath AP. A hyperpolarizing rod bipolar cell in the sea lamprey, Petromyzon marinus.. The Journal of experimental biology, 2022.
  9. Morshedian A, Sendek G, Ng SY, Boyd K, Radu RA, Liu M, Artemyev NO, Sampath AP, Fain GL. Reproducibility of the Rod Photoreceptor Response Depends Critically on the Concentration of the Phosphodiesterase Effector Enzyme.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2022.
  10. Fain GL, Sampath AP. Light responses of mammalian cones.. Pflugers Archiv : European journal of physiology, 2021.
  11. Frederiksen R, Morshedian A, Tripathy SA, Xu T, Travis GH, Fain GL, Sampath AP. Rod Photoreceptors Avoid Saturation in Bright Light by the Movement of the G Protein Transducin.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2021.
  12. Morshedian A, Huynh TH, Frederiksen R, Fain GL, Sampath AP. Pupillary light reflex of lamprey Petromyzon marinus.. Current biology : CB, 2021.
  13. Ingram NT, Fain GL, Sampath AP. Elevated energy requirement of cone photoreceptors.. Proceedings of the National Academy of Sciences of the United States of America, 2020.
  14. Zhang W, Frausto R, Chung DD, Griffis CG, Kao L, Chen A, Azimov R, Sampath AP, Kurtz I, Aldave AJ. Energy Shortage in Human and Mouse Models of SLC4A11-Associated Corneal Endothelial Dystrophies.. Investigative ophthalmology & visual science, 2020.
  15. Ellis EM, Frederiksen R, Morshedian A, Fain GL, Sampath AP. Separate ON and OFF pathways in vertebrate vision first arose during the Cambrian.. Current biology : CB, 2020.
  16. Chen NS, Ingram NT, Frederiksen R, Sampath AP, Chen J, Fain GL. Diminished Cone Sensitivity in cpfl3 Mice Is Caused by Defective Transducin Signaling.. Investigative ophthalmology & visual science, 2020.
  17. Peng YR, Sampath AP. LRR-ning the Rules: Synapse Organization in the Primary Rod Pathway.. Neuron, 2020.
  18. Ingram NT, Sampath AP, Fain GL. Membrane conductances of mouse cone photoreceptors.. The Journal of general physiology, 2020.
  19. Ingram NT, Sampath AP, Fain GL. Voltage-clamp recordings of light responses from wild-type and mutant mouse cone photoreceptors.. The Journal of general physiology, 2019.
  20. Wang T, Pahlberg J, Cafaro J, Frederiksen R, Cooper AJ, Sampath AP, Field GD, Chen J. Activation of Rod Input in a Model of Retinal Degeneration Reverses Retinal Remodeling and Induces Formation of Functional Synapses and Recovery of Visual Signaling in the Adult Retina.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2019.
  21. Morshedian A, Kaylor JJ, Ng SY, Tsan A, Frederiksen R, Xu T, Yuan L, Sampath AP, Radu RA, Fain GL, Travis GH. Light-Driven Regeneration of Cone Visual Pigments through a Mechanism Involving RGR Opsin in Müller Glial Cells.. Neuron, 2019.
  22. Fain G, Sampath AP. Rod and cone interactions in the retina.. F1000Research, 2018.
  23. Sarria I, Cao Y, Wang Y, Ingram NT, Orlandi C, Kamasawa N, Kolesnikov AV, Pahlberg J, Kefalov VJ, Sampath AP, Martemyanov KA. LRIT1 Modulates Adaptive Changes in Synaptic Communication of Cone Photoreceptors.. Cell reports, 2018.
  24. Martemyanov KA, Sampath AP. The Transduction Cascade in Retinal ON-Bipolar Cells: Signal Processing and Disease.. Annual review of vision science, 2017.
  25. Field GD, Sampath AP. Behavioural and physiological limits to vision in mammals.. Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2017.
  26. Pahlberg J, Frederiksen R, Pollock GE, Miyagishima KJ, Sampath AP, Cornwall MC. Voltage-sensitive conductances increase the sensitivity of rod photoresponses following pigment bleaching.. The Journal of physiology, 2017.
  27. Wang Y, Fehlhaber KE, Sarria I, Cao Y, Ingram NT, Guerrero-Given D, Throesch B, Baldwin K, Kamasawa N, Ohtsuka T, Sampath AP, Martemyanov KA. The Auxiliary Calcium Channel Subunit α2δ4 Is Required for Axonal Elaboration, Synaptic Transmission, and Wiring of Rod Photoreceptors.. Neuron, 2017.
  28. Ingram NT, Sampath AP, Fain GL. Why are rods more sensitive than cones?. The Journal of physiology, 2016.
  29. Cho A, Ratliff C, Sampath A, Weiland J. Changes in ganglion cell physiology during retinal degeneration influence excitability by prosthetic electrodes.. Journal of neural engineering, 2016.
  30. Cao Y, Sarria I, Fehlhaber KE, Kamasawa N, Orlandi C, James KN, Hazen JL, Gardner MR, Farzan M, Lee A, Baker S, Baldwin K, Sampath AP, Martemyanov KA. Mechanism for Selective Synaptic Wiring of Rod Photoreceptors into the Retinal Circuitry and Its Role in Vision.. Neuron, 2015.
  31. Majumder A, Pahlberg J, Muradov H, Boyd KK, Sampath AP, Artemyev NO. Exchange of Cone for Rod Phosphodiesterase 6 Catalytic Subunits in Rod Photoreceptors Mimics in Part Features of Light Adaptation.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015.
  32. Sarria I, Pahlberg J, Cao Y, Kolesnikov AV, Kefalov VJ, Sampath AP, Martemyanov KA. Sensitivity and kinetics of signal transmission at the first visual synapse differentially impact visually-guided behavior.. eLife, 2015.
  33. Reingruber J, Pahlberg J, Woodruff ML, Sampath AP, Fain GL, Holcman D. Detection of single photons by toad and mouse rods.. Proceedings of the National Academy of Sciences of the United States of America, 2013.
  34. Majumder A, Pahlberg J, Boyd KK, Kerov V, Kolandaivelu S, Ramamurthy V, Sampath AP, Artemyev NO. Transducin translocation contributes to rod survival and enhances synaptic transmission from rods to rod bipolar cells.. Proceedings of the National Academy of Sciences of the United States of America, 2013.
  35. Chen SK, Chew KS, McNeill DS, Keeley PW, Ecker JL, Mao BQ, Pahlberg J, Kim B, Lee SC, Fox MA, Guido W, Wong KY, Sampath AP, Reese BE, Kuruvilla R, Hattar S. Apoptosis regulates ipRGC spacing necessary for rods and cones to drive circadian photoentrainment.. Neuron, 2013.
  36. Mao W, Miyagishima KJ, Yao Y, Soreghan B, Sampath AP, Chen J. Functional comparison of rod and cone Gα(t) on the regulation of light sensitivity.. The Journal of biological chemistry, 2013.
  37. Cao Y, Pahlberg J, Sarria I, Kamasawa N, Sampath AP, Martemyanov KA. Regulators of G protein signaling RGS7 and RGS11 determine the onset of the light response in ON bipolar neurons.. Proceedings of the National Academy of Sciences of the United States of America, 2012.
  38. Arman AC, Sampath AP. Dark-adapted response threshold of OFF ganglion cells is not set by OFF bipolar cells in the mouse retina.. Journal of neurophysiology, 2012.
  39. Cho AK, Sampath AP, Weiland JD. Physiological response of normal and RD mouse retinal ganglion cells to electrical stimulation.. Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference, 2012.
  40. Farley RA, Sampath AP. Perspectives on: information coding in mammalian sensory physiology.. The Journal of general physiology, 2011.
  41. Doroudchi MM, Greenberg KP, Liu J, Silka KA, Boyden ES, Lockridge JA, Arman AC, Janani R, Boye SE, Boye SL, Gordon GM, Matteo BC, Sampath AP, Hauswirth WW, Horsager A. Virally delivered channelrhodopsin-2 safely and effectively restores visual function in multiple mouse models of blindness.. Molecular therapy : the journal of the American Society of Gene Therapy, 2011.
  42. Pahlberg J, Sampath AP. Visual threshold is set by linear and nonlinear mechanisms in the retina that mitigate noise: how neural circuits in the retina improve the signal-to-noise ratio of the single-photon response.. BioEssays : news and reviews in molecular, cellular and developmental biology, 2011.
  43. Cho AK, Sampath AP, Weiland JD. Physiological response of mouse retinal ganglion cells to electrical stimulation: effect of soma size.. Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference, 2011.
  44. Okawa H, Pahlberg J, Rieke F, Birnbaumer L, Sampath AP. Coordinated control of sensitivity by two splice variants of Gα(o) in retinal ON bipolar cells.. The Journal of general physiology, 2010.
  45. Arman AC, Sampath AP. Patch clamp recordings from mouse retinal neurons in a dark-adapted slice preparation.. Journal of visualized experiments : JoVE, 2010.
  46. Altimus CM, Güler AD, Alam NM, Arman AC, Prusky GT, Sampath AP, Hattar S. Rod photoreceptors drive circadian photoentrainment across a wide range of light intensities.. Nature neuroscience, 2010.
  47. Linton JD, Holzhausen LC, Babai N, Song H, Miyagishima KJ, Stearns GW, Lindsay K, Wei J, Chertov AO, Peters TA, Caffe R, Pluk H, Seeliger MW, Tanimoto N, Fong K, Bolton L, Kuok DL, Sweet IR, Bartoletti TM, Radu RA, Travis GH, Zagotta WN, Townes-Anderson E, Parker E, Van der Zee CE, Sampath AP, Sokolov M, Thoreson WB, Hurley JB. Flow of energy in the outer retina in darkness and in light.. Proceedings of the National Academy of Sciences of the United States of America, 2010.
  48. Okawa H, Miyagishima KJ, Arman AC, Hurley JB, Field GD, Sampath AP. Optimal processing of photoreceptor signals is required to maximize behavioural sensitivity.. The Journal of physiology, 2010.
  49. Matthews HR, Sampath AP. Photopigment quenching is Ca2+ dependent and controls response duration in salamander L-cone photoreceptors.. The Journal of general physiology, 2010.
  50. Singer JH, Glowatzki E, Moser T, Strowbridge BW, Bhandawat V, Sampath AP. Functional properties of synaptic transmission in primary sense organs.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009.
  51. Sampath AP, Fain GL. Setting the absolute threshold of vision.. F1000 biology reports, 2009.
  52. Miyagishima KJ, Cornwall MC, Sampath AP. Metabolic constraints on the recovery of sensitivity after visual pigment bleaching in retinal rods.. The Journal of general physiology, 2009.
  53. Cao Y, Masuho I, Okawa H, Xie K, Asami J, Kammermeier PJ, Maddox DM, Furukawa T, Inoue T, Sampath AP, Martemyanov KA. Retina-specific GTPase accelerator RGS11/G beta 5S/R9AP is a constitutive heterotrimer selectively targeted to mGluR6 in ON-bipolar neurons.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009.
  54. Okawa H, Sampath AP, Laughlin SB, Fain GL. ATP consumption by mammalian rod photoreceptors in darkness and in light.. Current biology : CB, 2008.
  55. Cao Y, Song H, Okawa H, Sampath AP, Sokolov M, Martemyanov KA. Targeting of RGS7/Gbeta5 to the dendritic tips of ON-bipolar cells is independent of its association with membrane anchor R7BP.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008.
  56. Okawa H, Sampath AP. Optimization of single-photon response transmission at the rod-to-rod bipolar synapse.. Physiology (Bethesda, Md.), 2007.
  57. Dunn FA, Doan T, Sampath AP, Rieke F. Controlling the gain of rod-mediated signals in the Mammalian retina.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006.
  58. Sampath AP, Strissel KJ, Elias R, Arshavsky VY, McGinnis JF, Chen J, Kawamura S, Rieke F, Hurley JB. Recoverin improves rod-mediated vision by enhancing signal transmission in the mouse retina.. Neuron, 2005.
  59. Field GD, Sampath AP, Rieke F. Retinal processing near absolute threshold: from behavior to mechanism.. Annual review of physiology, 2005.
  60. Sampath AP, Rieke F. Selective transmission of single photon responses by saturation at the rod-to-rod bipolar synapse.. Neuron, 2004.
  61. Sampath AP, Baylor DA. Molecular mechanism of spontaneous pigment activation in retinal cones.. Biophysical journal, 2002.