SYNAPTIC TRANSMISSION AND ITS MODULATION IN THE RETINA

点击翻译按钮获取中文摘要

Visual information is processed in the retina by synaptic interactions between neurons. The long-term objective of this research is to understand how communication between neurons at the inner plexiform layer (IPL) shapes the visual signals to ganglion cells, the outputs of the retina. Neuronal interactions at the IPL are mediated in part by the neurotransmitters glutamate and GABA. The first specific aim is to determine the roles of pre- and postsynaptic mechanisms that shape the ganglion cell excitatory synaptic responses mediated by glutamate. The mechanisms that will be studied include: 1) the role of postsynaptic desenstizing glutamate receptors, 2) the role of glutamate uptake by transporters, and 3) the role of presynaptic metabotropic glutamate receptors. The second specific aim is to determine the functional roles of inhibitory GABAc and GABAa receptors in synaptic processing at the IPL. This work will focus on: 1) the roles of presynaptic GABAc and postsynaptic GABAa receptors in mediating receptive field surround inputs at the IPL; 2) the roles of presynaptic GABAa and GABAc receptors during mammalian retinal development. The functional roles of GABA and glutamate will be determined by making whole-cell patch recordings from identified bipolar cells and ganglion cells in the retinal slice preparation. To determine the effects of receptor desensitization and uptake on excitatory response shaping, recordings will be made from ganglion cells in the absence or presence of pharmacological agents that selectively block these mechanisms. The role of metabotropic glutamate receptors will be assessed by determining the effects of specific receptor agonists and antagonists that may modulate excitatory transmission between bipolar cells and ganglion cells. The roles that different GABA receptors play in mediating surround signals in the IPL will be assessed by recording ganglion cell EPSCs when specific GABA receptor subtypes are selectively blocked. The roles of GABAa and GABAc receptors on functionally distinct subtypes of mammalian bipolar cells will be assessed by whole cell patch recording from identified bipolar cells to determine their receptor complements. The roles that these receptors on mammalian bipolar cells play in modulating excitatory transmission will also be assessed by recording from ganglion cells in the absence or presence of specific GABA receptor antagonists. To determine if GABA receptors on mammalian bipolar cells have also have developmental function, the complements of GABA receptors on distinct bipolar cells will be determined for different ages.