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 glutamte 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 underly 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.
- 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. J. Neurosci., 34: 3976-3981. *co-corresponding authors.
- 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.
- 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.
- Weick M, Demb JB (2011). Delayed rectifier Potassium channels contribute to contrast adaptation in mammalian retinal ganglion cells. Neuron, 71: 166-179.
- Wang YV, Weick M, Demb JB (2011). Spectral and temporal sensitivity of cone-mediated responses in mouse retinal ganglion cells. Journal of Neuroscience, 31: 7670-7681.
- Manookin MB, Weick M, Stafford BK, Demb JB (2010). NMDA receptor contributions to visual contrast coding. Neuron, 67: 280-293.