Brent Young

All Publications

• Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium. Molecular neurodegeneration Soucy, J. R., Aguzzi, E. A., Cho, J., Gilhooley, M. J., Keuthan, C., Luo, Z., Monavarfeshani, A., Saleem, M. A., Wang, X., Wohlschlegel, J., RReSTORe Consortium, Baranov, P., Di Polo, A., Fortune, B., Gokoffski, K. K., Goldberg, J. L., Guido, W., Kolodkin, A. L., Mason, C. A., Ou, Y., Reh, T. A., Ross, A. G., Samuels, B. C., Welsbie, D., Zack, D. J., Johnson, T. V., Fouda, A. Y., Ashok, A., Moshiri, A., Chedotal, A., Reed, A. A., Askary, A., Su, A. A., La Torre, A., Jalligampala, A., Silva-Lepe, A., Das, A., Wirostko, B., Frankfort, B. J., Sivyer, B., Alapure, B., Young, B., Clark, B., Jones, B. W., Hellmer, C., Mitchell, C., Ufongene, C., Goldman, D., Feldheim, D., Gutmann, D. H., Calkins, D. J., Krizaj, D., Gamm, D. M., Lozano, D. C., Bovenkamp, D. E., Chen, D. F., Cordero, E. V., Trakhtenberg, E. F., Tian, F., Zhou, F., McLellan, G. J., Quigley, H. A., Serhan, H. A., Tribble, J. R., Meyer, J., Gross, J., Mumm, J. S., Sivak, J. M., Zhang, J. S., Do, J. L., Crowston, J., Chen, J., McGregor, J., Vinnakota, K. C., Huang, K., Peynshaert, K., Uyhazi, K. E., Martin, K., Muller, K., Park, K. K., Cho, K., Chang, K., Benowitz, L., Levin, L. A., Todd, L., De Groef, L., Moons, L., Alarcon-Martinez, L., Singh, M. S., Vidal-Sanz, M., Silveira, M. S., Pavlou, M., Veldman, M. B., Van Hook, M., Samuel, M., Hu, M., Peng, M., Young, M., Cayouette, M., Geranmayeh, M. H., Woodworth, M., Vetter, M., Marsh-Armstrong, N. R., Williams, P. A., Rasiah, P. K., Subramanian, P., Cui, Q. N., Sappington, R. M., Amine, R., Eva, R., Johnston, R. J., Giger, R. J., Ethier, R., Abed, S., Momin, S. N., Blackshaw, S., Liddelow, S. A., Mary, S., Atolagbe, S., Varadarajan, S., Nabhan, T. I., Khatib, T., Sharma, T. P., Brunner, T., Greenwell, T., Rex, T. S., Watkins, T., Badea, T. C., Vrathasha, V., Chavali, V. R., Oliveira-Valenca, V. M., Tai, W. L., Batchelor, W. M., Yang, X., Park, Y., Pan, Y. 2023; 18 (1): 64

  Abstract

  Retinal ganglion cell (RGC) death in glaucoma and other optic neuropathies results in irreversible vision loss due to the mammalian central nervous system's limited regenerative capacity. RGC repopulation is a promising therapeutic approach to reverse vision loss from optic neuropathies if the newly introduced neurons can reestablish functional retinal and thalamic circuits. In theory, RGCs might be repopulated through the transplantation of stem cell-derived neurons or via the induction of endogenous transdifferentiation. The RGC Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) Consortium was established to address the challenges associated with the therapeutic repair of the visual pathway in optic neuropathy. In 2022, the RReSTORe Consortium initiated ongoing international collaborative discussions to advance the RGC repopulation field and has identified five critical areas of focus: (1) RGC development and differentiation, (2) Transplantation methods and models, (3) RGC survival, maturation, and host interactions, (4) Inner retinal wiring, and (5) Eye-to-brain connectivity. Here, we discuss the most pertinent questions and challenges that exist on the path to clinical translation and suggest experimental directions to propel this work going forward. Using these five subtopic discussion groups (SDGs) as a framework, we suggest multidisciplinary approaches to restore the diseased visual pathway by leveraging groundbreaking insights from developmental neuroscience, stem cell biology, molecular biology, optical imaging, animal models of optic neuropathy, immunology & immunotolerance, neuropathology & neuroprotection, materials science & biomedical engineering, and regenerative neuroscience. While significant hurdles remain, the RReSTORe Consortium's efforts provide a comprehensive roadmap for advancing the RGC repopulation field and hold potential for transformative progress in restoring vision in patients suffering from optic neuropathies.

  View details for DOI 10.1186/s13024-023-00655-y

  View details for PubMedID 37735444

• Campana cells in mammalian retinas Du, R., Young, B., Wang, P., Tian, N. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023

  View details for Web of Science ID 001053758304268

• An uncommon neuronal class conveys visual signals from rods and cones to retinal ganglion cells. Proceedings of the National Academy of Sciences of the United States of America Young, B. K., Ramakrishnan, C., Ganjawala, T., Wang, P., Deisseroth, K., Tian, N. 2021; 118 (44)

  Abstract

  Neurons in the central nervous system (CNS) are distinguished by the neurotransmitter types they release, their synaptic connections, morphology, and genetic profiles. To fully understand how the CNS works, it is critical to identify all neuronal classes and reveal their synaptic connections. The retina has been extensively used to study neuronal development and circuit formation. Here, we describe a previously unidentified interneuron in mammalian retina. This interneuron shares some morphological, physiological, and molecular features with retinal bipolar cells, such as receiving input from photoreceptors and relaying visual signals to retinal ganglion cells. It also shares some features with amacrine cells (ACs), particularly Aii-ACs, such as their neurite morphology in the inner plexiform layer, the expression of some AC-specific markers, and possibly the release of the inhibitory neurotransmitter glycine. Thus, we unveil an uncommon interneuron, which may play an atypical role in vision.

  View details for DOI 10.1073/pnas.2104884118

  View details for PubMedID 34702737

• The Susceptibility of Retinal Ganglion Cells to Optic Nerve Injury is Type Specific. Cells Yang, N., Young, B. K., Wang, P., Tian, N. 2020; 9 (3)

  Abstract

  Retinal ganglion cell (RGC) death occurs in many eye diseases, such as glaucoma and traumatic optic neuropathy (TON). Increasing evidence suggests that the susceptibility of RGCs varies to different diseases in an RGC type-dependent manner. We previously showed that the susceptibility of several genetically identified RGC types to N-methyl-D-aspartate (NMDA) excitotoxicity differs significantly. In this study, we characterize the susceptibility of the same RGC types to optic nerve crush (ONC). We show that the susceptibility of these RGC types to ONC varies significantly, in which BD-RGCs are the most resistant RGC type while W3-RGCs are the most sensitive cells to ONC. We also show that the survival rates of BD-RGCs and J-RGCs after ONC are significantly higher than their survival rates after NMDA excitotoxicity. These results are consistent with the conclusion that the susceptibility of RGCs to ONC varies in an RGC type-dependent manner. Further, the susceptibilities of the same types of RGCs to ONC and NMDA excitotoxicity are significantly different. These are valuable insights for understanding of the selective susceptibility of RGCs to various pathological insults and the development of a strategy to protect RGCs from death in disease conditions.

  View details for DOI 10.3390/cells9030677

  View details for PubMedID 32164319

  View details for PubMedCentralID PMC7140711

• NMDA receptor activity regulates synaptic connections between retinal ganglion and bipolar cells Young, B., Sanchez, C., Ramakrishnan, C., Wang, P., Deisseroth, K., Tian, N. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442912505173

• An unique subtype of BCs provides excitatory input to both ON and OFF synaptic pathways from both rods and cones in the retina Tian, N., Young, B., Ramakrishnan, C., Wang, P., Deisseroth, K., Ganjawala, T. H., Pan, Z. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442912509023

• Virtual reality method to analyze visual recognition in mice. PloS one Young, B. K., Brennan, J. N., Wang, P., Tian, N. 2018; 13 (5): e0196563

  Abstract

  Behavioral tests have been extensively used to measure the visual function of mice. To determine how precisely mice perceive certain visual cues, it is necessary to have a quantifiable measurement of their behavioral responses. Recently, virtual reality tests have been utilized for a variety of purposes, from analyzing hippocampal cell functionality to identifying visual acuity. Despite the widespread use of these tests, the training requirement for the recognition of a variety of different visual targets, and the performance of the behavioral tests has not been thoroughly characterized. We have developed a virtual reality behavior testing approach that can essay a variety of different aspects of visual perception, including color/luminance and motion detection. When tested for the ability to detect a color/luminance target or a moving target, mice were able to discern the designated target after 9 days of continuous training. However, the quality of their performance is significantly affected by the complexity of the visual target, and their ability to navigate on a spherical treadmill. Importantly, mice retained memory of their visual recognition for at least three weeks after the end of their behavioral training.

  View details for DOI 10.1371/journal.pone.0196563

  View details for PubMedID 29768429

  View details for PubMedCentralID PMC5955493

• Adult zebra finches rehearse highly variable song patterns during sleep. PeerJ Young, B. K., Mindlin, G. B., Arneodo, E., Goller, F. 2017; 5: e4052

  Abstract

  Brain activity during sleep is fairly ubiquitous and the best studied possible function is a role in memory consolidation, including motor memory. One suggested mechanism of how neural activity effects these benefits is through reactivation of neurons in patterns resembling those of the preceding experience. The specific patterns of motor activation replayed during sleep are largely unknown for any system. Brain areas devoted to song production in the songbird brain exhibit spontaneous song-like activity during sleep, but single cell neural recordings did not permit detection of the specific song patterns. We have now discovered that this sleep activation can be detected in the muscles of the vocal organ, thus providing a unique window into song-related brain activity at night. We show that male zebra finches (Taeniopygia guttata) frequently exhibit spontaneous song-like activity during the night, but that the fictive song patterns are highly variable and uncoordinated compared to the highly stereotyped day-time song production. This substantial variability is not consistent with the idea that night-time activity replays day-time experiences for consolidation. Although the function of this frequent activation is unknown, it may represent a mechanism for exploring motor space or serve to generate internal error signals that help maintain the high stereotypy of day-time song. In any case, the described activity supports the emerging insight that brain activity during sleep may serve a variety of functions.

  View details for DOI 10.7717/peerj.4052

  View details for PubMedID 29158983

  View details for PubMedCentralID PMC5694654

• Retinal ganglion cell subtype specific circuits in retina Tian, N., Young, B., Huang, K., Wang, P., Ramakrishnan, C., Deisseroth, K. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2016

  View details for Web of Science ID 000394210603383

• From the retina to the brain: retinal ganglion cell subtype specific visual circuits Young, B., Wang, P., Ramakrishnan, C., Deisseroth, K., Tian, N. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2016

  View details for Web of Science ID 000394210201132