The overall goal of this program is to better understand visual information processing in the mammalian inner retina by defining and characterizing its transmitter systems, cell morphology and microcircuitry. The focus of these studies is on GABA, a prominent inhibitory transmitter that is expressed in a high percentage of amacrine cells, and on neuroactive peptides that are expressed in subpopulations of amacrine cells and co-occur with GABA Emphasis will be placed on characterizing the bipolar and amacrine cell types that these transmitters act upon by determining the distribution and cellular localization of their receptors. These studies will also identity the cells that contain GABA plasma membrane transporters to define the sites of GABA uptake and inactivation at the cellular level. The following are the specific aims of this proposal.
Specific aim 1 will identity the GABA-A receptor subunits and determine their distribution and cellular localization to elucidate the sites of action of GABA-containing amacrine and interplexiform cells.
Specific aim 2 will define the expression and cellular localization of tachykinin (TK) and vasoactive intestinal polypeptide (VIP) receptor mRNAs to elucidate the sites of action of TK peptides and VIP, which are located in morphologically distinct amacrine cell populations and co-expressed with GABA.
Specific aim 3 will identity the expression and cellular localization of the GABA plasma membrane transporters to elucidate the cellular sites of GABA uptake and inactivation These experiments will utilize sequence specific oligonucleotide and RNA probes, and specific antibodies to the GABA-A receptor subunits, TK and VIP receptors, and GABA transporters to accomplish the experimental objectives of this application Proposed studies will utilize both in situ hybridization and immunohistochemistry with rat and rabbit retinal model systems. These studies will provide important insights for an understanding of the role of a major inhibitory transmitter, GABA, and of neuroactive peptides that act as modulatory substances in the inner plexiform layer. These studies will thus provide the basis for a better understanding of visual information processing in the retina. These objectives are consistent with the health related goals of the National Eye Institute to develop more effective treatments and ultimately to prevent retinal diseases by defining the neurochemical and structural organization of the retina.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004067-15
Application #
2158980
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1981-07-06
Project End
1999-06-30
Budget Start
1995-07-01
Budget End
1996-06-30
Support Year
15
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Travis, Amanda M; Heflin, Stephanie J; Hirano, Arlene A et al. (2018) Dopamine-Dependent Sensitization of Rod Bipolar Cells by GABA Is Conveyed through Wide-Field Amacrine Cells. J Neurosci 38:723-732
Pérez de Sevilla Müller, Luis; Azar, Shaghauyegh S; de Los Santos, Janira et al. (2017) Prox1 Is a Marker for AII Amacrine Cells in the Mouse Retina. Front Neuroanat 11:39
Matynia, Anna; Nguyen, Eileen; Sun, Xiaoping et al. (2016) Peripheral Sensory Neurons Expressing Melanopsin Respond to Light. Front Neural Circuits 10:60
Wang, Yanling; Wang, Wenyao; Liu, Jessica et al. (2016) Protective Effect of ALA in Crushed Optic Nerve Cat Retinal Ganglion Cells Using a New Marker RBPMS. PLoS One 11:e0160309
Pérez de Sevilla Müller, Luis; Sargoy, Allison; Fernández-Sánchez, Laura et al. (2015) Expression and cellular localization of the voltage-gated calcium channel ?2?3 in the rodent retina. J Comp Neurol 523:1443-60
Hoon, Mrinalini; Sinha, Raunak; Okawa, Haruhisa et al. (2015) Neurotransmission plays contrasting roles in the maturation of inhibitory synapses on axons and dendrites of retinal bipolar cells. Proc Natl Acad Sci U S A 112:12840-5
Vuong, Helen E; Hardi, Claudia N; Barnes, Steven et al. (2015) Parallel Inhibition of Dopamine Amacrine Cells and Intrinsically Photosensitive Retinal Ganglion Cells in a Non-Image-Forming Visual Circuit of the Mouse Retina. J Neurosci 35:15955-70
Vuong, H E; Pérez de Sevilla Müller, L; Hardi, C N et al. (2015) Heterogeneous transgene expression in the retinas of the TH-RFP, TH-Cre, TH-BAC-Cre and DAT-Cre mouse lines. Neuroscience 307:319-37
Fernández-Sánchez, Laura; de Sevilla Müller, Luis Pérez; Brecha, Nicholas C et al. (2014) Loss of outer retinal neurons and circuitry alterations in the DBA/2J mouse. Invest Ophthalmol Vis Sci 55:6059-72
He, Meihua; Pan, Hong; Chang, Raymond Chuen-Chung et al. (2014) Activation of the Nrf2/HO-1 antioxidant pathway contributes to the protective effects of Lycium barbarum polysaccharides in the rodent retina after ischemia-reperfusion-induced damage. PLoS One 9:e84800

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