Retinal ganglion cell responses in lower vertebrates signal static and dynamic contrast in the visual image. This information is extracted through receptive field (RF) functional properties that include center/surround organization, spatial discrimination, orientation sensitivity, directional selectivity, and velocity tuning. Similar RF properties are found in the retinas and visual CNS of mammals. Thus, studies of the retinal circuitry and synaptic pharmacology underlying these RF properties in turtle will be invaluable for understanding mammalian CNS function. These experiments focus on the interaction of retinal neurons in the innerplexiform layer (IPL), since IPL interactions underlie the processing of complex static and dynamic contrast features. Bipolar (BC)-ganglion (GC) or bipolar (BC)-amacrine (AC)-ganglion (GC) cell pathways may use amino acid and monamine transmitters (in bipolar and amacrine cells) as well as cholinergics, peptides, and catecholamines (in amacrine cells). Specific agonists, antagonists/receptor blockers, and modulators of putative bipolar and amacrine transmitters will be applied by superfusion or iontophoresis to eyecup or isolated retina preparations. The actions of the putative transmitters will be evaluated using extracellular recordings of GC spike rate variations, and intracellular recordings of BC, AC, and GC membrane potential, conductance changes, and reversal potentials. Antagonists and modulators of effective exogenous agonists will be tested against endogenous transmitters at synapses in functionally specific pathways. Drifting sinusoidal gratings and temporal noise modulated light intensity will be used to assess, via transfer functions, changes resulting from pharmacological manipulation of IPL synapses on RF spatial organization and kinetics. The specific functional role of two peptidergic amacrine transmitters, substance P (SP) and enkephalin (ENK), is also of special interest. Peptide action is usually prolonged and of slow onset; peptides are often colocalized with conventional transmitters in presynaptic endings. The putative modulatory role or temporally specialized function (delayed inhibition of sustained BC inputs to transient GC) of these peptides will be investigated. The enhancement of GC activity in response to activation of a centrifugal pathway to IPL from mesencephalon involves ENK. One mechanism of this feedback disinhibitory action to be analyzed is opiate modulation of GABA AC interneurons.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY003383-08
Application #
3257711
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1980-09-01
Project End
1989-04-30
Budget Start
1988-05-01
Budget End
1989-04-30
Support Year
8
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Schepens Eye Research Institute
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02114