Adaptation, Physiological; Neurophysiology; Retinal Ganglion Cells; Synapses; Retinal Cone Photoreceptor Cells; Retinal Bipolar Cells
The broad goal of my laboratory is to understand how information is processed by the central nervous system (CNS) at the level of specific cell types and circuits. As our model system, we work on the mammalian retina. The retina has a clear role in behavior, and many of its cell types and circuits are well defined. Furthermore, retina is one area of the CNS that can be studied in vitro while presenting the natural stimulus it was designed to encode.
We study functional circuitry by whole-cell patch clamp electrophysiology of identified retinal cell types, labeled with fluorescent markers (transgenic and viral approaches) and visualized in living tissue (2-photon microscopy). We perform quantitative analysis of cellular morphology and synaptic connections (confocal microscopy); and functional properties of light-evoked responses (computational modeling). We are also studying neurotransmitter release by direct imaging of fluorescent sensors, including the glutamate biosensor intensity-based glutamate-sensing fluorescent reporter (iGluSnFR).
Our immediate goals are to define and characterize novel interneuron pathways in the mouse retina using optogenetic, electrophysiology and inactivation methods. We are also studying the cellular mechanisms that underlie contrast adaptation in retinal circuitry. We will also apply our methods to reveal synaptic dysfunction in mouse models of eye disease.
Extensive Research Description
Current projects include: optogenetic techniques to define new interneuron circuits in the retina; optical imaging of neurotransmitter release in retinal circuitry; elucidating the role of NMDA receptors in visual processing; cellular basis of visual adaptation; mechanisms of retinal disease.
Function and circuitry of VIP+ interneurons in the mouse retina
Park SJH, Borghuis BG, Rahmani P, Zeng Q, Kim IJ+, Demb JB+ (2015). Function and circuitry of VIP+ interneurons in the mouse retina. Journal of Neuroscience, 35:10685-10700. +co-senior authors.
Excitatory synaptic inputs to mouse On-Off direction-selective retinal ganglion cells lack direction tuning
Park SJH, Kim IJ, Looger LL, Demb JB*, Borghuis BG* (2014). Excitatory synaptic inputs to mouse On-Off direction-selective retinal ganglion cells lack direction tuning. Journal of Neuroscience, 34: 3976-3981. *co-corresponding authors.
Adaptation to background light enables contrast coding at rod bipolar cell synapses
Ke JB*, Wang YV*, Borghuis BG, Cembrowski MS, Riecke H, Kath WL, Demb JB+, Singer JH+ (2014). Adaptation to background light enables contrast coding at rod bipolar cell synapses. Neuron, 81: 388-401. *co-first authors, +co-corresponding authors.
Two-photon imaging of nonlinear glutamate release dynamics at bipolar cell synapses in the mouse retina
Borghuis BG, Marvin JS, Looger LL, Demb JB (2013). Two-photon imaging of nonlinear glutamate release dynamics at bipolar cell synapses in the mouse retina. Journal of Neuroscience, 33: 10972-10985.
Delayed rectifier Potassium channels contribute to contrast adaptation in mammalian retinal ganglion cells
Weick M, Demb JB (2011). Delayed rectifier Potassium channels contribute to contrast adaptation in mammalian retinal ganglion cells. Neuron, 71: 166-179.
NMDA receptor contributions to visual contrast coding
Manookin MB, Weick M, Stafford BK, Demb JB (2010). NMDA receptor contributions to visual contrast coding. Neuron, 67: 280-293.
Full List of PubMed Publications
- Cui Y, Wang YV, Park SJ, Demb JB, Butts DA: Divisive suppression explains high-precision firing and contrast adaptation in retinal ganglion cells. Elife. 2016 Nov 14; 2016 Nov 14. PMID: 27841746
- Clark DA, Demb JB: Parallel Computations in Insect and Mammalian Visual Motion Processing. Curr Biol. 2016 Oct 24. PMID: 27780048
- Byun H, Kwon S, Ahn HJ, Liu H, Forrest D, Demb JB, Kim IJ: Molecular features distinguish ten neuronal types in the mouse superficial superior colliculus. J Comp Neurol. 2016 Aug 1; 2016 Jan 26. PMID: 26713509
- Mortensen LS, Park SJ, Ke JB, Cooper BH, Zhang L, Imig C, Löwel S, Reim K, Brose N, Demb JB, Rhee JS, Singer JH: Complexin 3 Increases the Fidelity of Signaling in a Retinal Circuit by Regulating Exocytosis at Ribbon Synapses. Cell Rep. 2016 Jun 7; 2016 May 26. PMID: 27239031
- Demb JB, Singer JH: Mind the Gap Junctions: The Importance of Electrical Synapses to Visual Processing. Neuron. 2016 Apr 20. PMID: 27100191
- Demb JB, Singer JH: Functional Circuitry of the Retina. Annu Rev Vis Sci. 2015 Nov 24. PMID: 28532365
- Park SJ, Borghuis BG, Rahmani P, Zeng Q, Kim IJ, Demb JB: Function and Circuitry of VIP+ Interneurons in the Mouse Retina. J Neurosci. 2015 Jul 29. PMID: 26224854
- Stafford BK, Manookin MB, Singer JH, Demb JB: NMDA and AMPA receptors contribute similarly to temporal processing in mammalian retinal ganglion cells. J Physiol. 2014 Nov 15; 2014 Sep 12. PMID: 25217374
- Borghuis BG, Looger LL, Tomita S, Demb JB: Kainate receptors mediate signaling in both transient and sustained OFF bipolar cell pathways in mouse retina. J Neurosci. 2014 Apr 30. PMID: 24790183
- Park SJ, Kim IJ, Looger LL, Demb JB, Borghuis BG: Excitatory synaptic inputs to mouse on-off direction-selective retinal ganglion cells lack direction tuning. J Neurosci. 2014 Mar 12. PMID: 24623775
- Stafford BK, Park SJ, Wong KY, Demb JB: Developmental changes in NMDA receptor subunit composition at ON and OFF bipolar cell synapses onto direction-selective retinal ganglion cells. J Neurosci. 2014 Jan 29. PMID: 24478373
- Ke JB, Wang YV, Borghuis BG, Cembrowski MS, Riecke H, Kath WL, Demb JB, Singer JH: Adaptation to background light enables contrast coding at rod bipolar cell synapses. Neuron. 2014 Jan 22; 2013 Dec 26. PMID: 24373883
- Borghuis BG, Marvin JS, Looger LL, Demb JB: Two-photon imaging of nonlinear glutamate release dynamics at bipolar cell synapses in the mouse retina. J Neurosci. 2013 Jul 3. PMID: 23825403
- Demb JB, Singer JH: Intrinsic properties and functional circuitry of the AII amacrine cell. Vis Neurosci. 2012 Jan. PMID: 22310372