Joshua Singer
Professor
Contact
Email: jhsinger@umd.edu
Office Phone: 301.405.9784
Fax: 301.314.9489
Office Address: 3210 Biology-Psychology Building
Research Interests and Goals
Generally, I want to understand how the output of a neural circuit reflects the behaviors of the individual synapses and neurons that compose it. The mammalian retina is a model circuit well suited to the study of this issue: it is well-characterized anatomically and physiologically, but the nature of synaptic transmission between its component neurons is understood poorly.
Contact
Email: jhsinger@umd.edu
Office Phone: 301.405.9784
Fax: 301.314.9489
Office Address: 3210 Biology-Psychology Building
Research Interests and Goals
Generally, I want to understand how the output of a neural circuit reflects the behaviors of the individual synapses and neurons that compose it. The mammalian retina is a model circuit well suited to the study of this issue: it is well-characterized anatomically and physiologically, but the nature of synaptic transmission between its component neurons is understood poorly.
Specifically, my laboratory studies a specialized group of neurons that compose a retinal circuit called the rod bipolar cell pathway (see figure at right). This pathway functions during night vision, and signaling within it begins when rods absorb light. Rods are the receptive cells that are most sensitive to light: single photons can activate rods and cause very small electrical signals to be generated within them. Electrical signals from rods are propagated first to rod bipolar cells, then to AII amacrine cells (AIIs), and finally to ganglion cells, the neurons that project to the brain.
Signaling within the rod bipolar cell pathway is significant because the circuit is sensitive enough to encode small rod signals generated by single photons and flexible enough to encode much larger rod signals that arise from the widely variable light intensities within ever-changing natural scenes. Thus, the rod bipolar pathway exhibits both sensitivity and a wide operating, or dynamic, range. My laboratory studies two aspects of signaling in the rod bipolar pathway: synaptic transmission from rod bipolar cells to AIIs and processing of rod bipolar cell outputs by AIIs and ganglion cells. We assess synaptic transmission by recording neurons' electrical activity. Recordings are complemented by anatomical and computational analyses and ultimately used to understand features of the retina's responses to visual stimuli.
From our studies, we hope not only to understand signaling within the rod bipolar pathway but also to generate a broader understanding of how the properties of neurons and their synapses give rise to circuit behavior. Our work is of interest to sensory neuroscientists specifically and to neuroscientists generally: the former because it relates to the coding of sensory information by ribbon synapses and retinal circuits and the latter because it provides an understanding of the basic principles of synaptic communication between neurons and neural circuit function. As well, our work may provide insights that serve as a basis for therapies for human diseases that affect the first stages of visual processing. Such diseases include retinitis pigmentosa and macular degeneration.
All Publications (via Google Scholar; via PubMed)
Recent Publications
Original, peer-reviewed research articles (UMD undergraduates underlined)
Park, S, Lieberman, EE, Ke, J-B, Rho, N, Ghorbani, P, Rahmani, P, Jun, N-Y, Lee, H-J, Kim, I-J, Briggman, KL, Demb, JB, & Singer, JH. (2020) Connectomic analysis reveals an interneuron with an integral role in the retinal circuit for night vision. eLife 2020;9:e56077.
Fernandez, DC, Fogerson, MP, Ospri, LL, Thomsen, MB, Layne, RM, Severin, D, Zhan, J, Singer, JH, Kirkwood, A, Zhao, H, Berson, D, & Hattar, S. (2018) Light affects mood through a novel retina-brain circuit. Cell (175): 1-14.
Graydon, CW, Lieberman, EE, Rho, N, Briggman, KL, Singer, JH, & Diamond, JS. (2018) Synaptic transfer between rod and cone pathways mediated by AII amacrine cells in the mouse retina Current Biology (28): 1–13.
Park, SJH, Pottackal, J, Ke, J-B, Jun, NY, Rahmani, P, Kim, I-J, Singer, JH, & Demb, JB. (2018) Convergence and divergence of CRH amacrine cells in mouse retinal circuitry. J. Neurosci. 38(15): 3753–3766.
Mortensen, LS, Park, SJH, Ke, J-b, Cooper, BH, Zhang, L, Imig, C, Löwel, S, Reim, K, Brose, N, Demb, JB, Rhee, J-S, and Singer, JH. (2016) Complexin 3 increases the fidelity of signaling in a retinal circuit by regulating exocytosis at ribbon synapses. Cell Rep. 15: 1-12
Pallotto, M, Watkins, PV, Fubara, B, Singer, JH, and Briggman, KL. (2015) Extracellular space preservation benefits the anatomical reconstruction of neural circuits. eLife Dec 9;4. pii: e08206.
Firl, A, Ke, J-B, Zhang, L, Singer, JH, and Feller, MB. (2015) Elucidating the role of AII amacrine cells in glutamatergic retinal waves. J. Neurosci. 35(4): 1675-1686.
Stafford, BK, Manookin, MB, Singer, JH, Demb, JB. (2014) NMDA and AMPA receptors contribute similarly to temporal processing in mammalian retinal ganglion cells. J. Physiol. 592(22): 4877-4889.
Choi, H, Zhang, L, Cembrowski, MS, Sabottke, CF, Markowitz, AL, Butts, DA, Kath, WL, Singer, JH, and Riecke, H. (2014) Intrinsic bursting of AII amacrine cells underlies oscillations in the rd1 mouse retina. J. Neurophysiol. 112(6): 1491-1504
Mehta, B, Ke, J-B, Zhang, L, Baden, AD, Markowitz, AL, Nayak, S, Briggman, KL, Zenisek, DP, and Singer, JH (2014) Global Ca2+ signaling drives ribbon-independent synaptic transmission at rod bipolar cell synapses. J. Neurosci. 34(18): 6233– 6244.
Margolis, DJ, Gartland, AJ, Singer, JH, and Detwiler, PB (2014) Network oscillations drive correlated spiking of ON and OFF ganglion cells in the rd1 mouse model of retinal degeneration. PLoS One 9(1): e86253. doi:10.1371/journal.pone.0086253
Ke, J, Wang, YB, Borguis, BG, Cembrowski, MS, Kath, WL, Riecke, H, Demb, JB, and Singer, JH (2014)Adaptation to background light enables contrast coding at rod bipolar cell synapses. Neuron 81(2): 388-401.
Cembrowski, MS, Logan, SM, Tian, M, Jia, L, Li, W, Kath, WL, Riecke, H, and Singer, JH (2012) The mechanisms of repetitive spike generation in an axonless retinal interneuron. Cell Reports 1: 155-66.
Reviews and Commentaries
Pangrsic, T, Singer, JH, and Koschak, A. (2018) Voltage-Gated Calcium Channels: Key Players in Sensory Coding in the Retina and the Inner Ear. Physiol. Rev. 98(4):2063-2096.
Demb, JB and Singer, JH (2016) Mind the gap junctions: the importance of electrical synapes to visual processing. Neuron 90(2): 207-09
Demb, JB and Singer, JH (2015) Functional circuitry of the retina. Annu Rev Vis Sci 1: 263–289
Demb, J.B. and Singer JH (2012) Intrinsic properties and functional circuitry of the All amacrine cell. Vis. Neurosci. 29: 51-60
Singer, JH, Glowatzki, E, Moser, T, Strowbridge, B, Bhandawat, V, and Sampath, AP. (2009) Functional Properties of Synaptic Transmission in Primary Sense Organs. J. Neurosci., 29(41): 12802-6.
Singer, JH (2008) GABA is an endogenous agonist of glycine receptors. Neuron: 57(4): 475-77.
Singer, JH (2007) Multivesicular release and saturation of glutamatergic signaling at retinal ribbon synapses.J. Physiol. 580(1): 23-29.
Awards
2011 Research to Prevent Blindness Special Scholar Award for Retinitis Pigmentosa
2007-2009 Alfred P. Sloan Foundation Research Fellowship
2002-2007 NINDS Career Development (K-22) Award
Teaching
Classes
BSCI440: Mammalian Physiology
BSCI339G: Advanced Physiology
BSCI338N: Diseases of the Nervous System
BSCI279: Readings in Physiology
Policies
Registration for BSCI279 is by permisison only.
Education
Sc.B., Brown University, 1993
Ph.D, University of Washington, 1998
Postdoctoral Research, NIH, 1998-2004