The overall objective of this project is to understand in detail the physiological and pharmacological mechanisms underlying excitatory and inhibitory light-evoked signals, which mediate the center-surround antagonistic receptive field (CSARF) organization of retinal bipolar cells. We plan to use the whole-cell voltage clamp technique to study light-evoked responses of morphologically identified bipolar cells in dark-adapted salamander retinal slices, or in some experiments, use the microelectrode voltage recording technique in flat-mounted retinas to compensate for the limitations of the voltage clamp technique. As a continuation and extension of our studies in the last grant period, this application addresses 6 specific aims focused on the excitatory synaptic inputs mediating bipolar cell center light responses (aim 1, 3 and 4), and the inhibitory synaptic inputs mediating the surround light responses (aim 1, 2, 5 and 6).
These aims focus on understandings of (1) the relative contributions of cation and chloride conductance changes to light responses in different types of bipolar cells, (2) amacrine cell and horizontal cell inhibitory inputs to surround responses of various types of depolarizing bipolar cells (DBCs), (3) differences in physiological properties and subunit compositions between glutamate receptors in rod- and cone-dominated hyperpolarizing bipolar cells (HBCrs and HBCcs), (4) kinetics of glutamate receptors and spontaneous excitatory postsynaptic currents (sEPSCs) in HBCrs and HBCcs, (5) differences in unitary conductance, kinetics and antagonist sensitivity between glycine receptors in various types of bipolar cells, and (6) response sensitivity and relative amount of rod/cone inputs of dark- and light-adapted amacrine cells and effects of GABA and glycine receptor antagonists on their light-evoked inputs to bipolar cells. Results obtained will provide detailed information on how individual synaptic events mediate the CSARF organization, the ubiquitous functional units across species and the basic code for spatial information processing in the visual system. Additionally, they will reveal how abnormalities (e.g. excess extracellular glutamate) in retinal synapses may influence retinal function in diseased states.
|Pang, Ji-Jie; Yang, Zhuo; Jacoby, Roy A et al. (2018) Cone synapses in mammalian retinal rod bipolar cells. J Comp Neurol 526:1896-1909|
|Cowan, Cameron S; Sabharwal, Jasdeep; Seilheimer, Robert L et al. (2017) Distinct subcomponents of mouse retinal ganglion cell receptive fields are differentially altered by light adaptation. Vision Res 131:96-105|
|Tse, Dennis Y; Kim, Seong Jae; Chung, Inyoung et al. (2017) The ocular toxicity and pharmacokinetics of simvastatin following intravitreal injection in mice. Int J Ophthalmol 10:1361-1369|
|He, Feng; Agosto, Melina A; Anastassov, Ivan A et al. (2016) Phosphatidylinositol-3-phosphate is light-regulated and essential for survival in retinal rods. Sci Rep 6:26978|
|Wang, Jing; Jacoby, Roy; Wu, Samuel M (2016) Physiological and morphological characterization of ganglion cells in the salamander retina. Vision Res 119:60-72|
|Cowan, Cameron S; Abd-El-Barr, Muhammad; van der Heijden, Meike et al. (2016) Connexin 36 and rod bipolar cell independent rod pathways drive retinal ganglion cells and optokinetic reflexes. Vision Res 119:99-109|
|Tse, Dennis Y; Lotfi, Parisa; Simons, David L et al. (2015) Electrophysiological and Histological Characterization of Rod-Cone Retinal Degeneration and Microglia Activation in a Mouse Model of Mucopolysaccharidosis Type IIIB. Sci Rep 5:17143|
|Pang, Ji-Jie; Frankfort, Benjamin J; Gross, Ronald L et al. (2015) Elevated intraocular pressure decreases response sensitivity of inner retinal neurons in experimental glaucoma mice. Proc Natl Acad Sci U S A 112:2593-8|
|Eblimit, Aiden; Nguyen, Thanh-Minh T; Chen, Yiyun et al. (2015) Spata7 is a retinal ciliopathy gene critical for correct RPGRIP1 localization and protein trafficking in the retina. Hum Mol Genet 24:1584-601|
|Khan, A Kareem; Tse, Dennis Y; van der Heijden, Meike E et al. (2015) Prolonged elevation of intraocular pressure results in retinal ganglion cell loss and abnormal retinal function in mice. Exp Eye Res 130:29-37|
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