This proposal focusses on providing a description of the components of neural pathways in the retina responsible for the modulation of visual signals. For example, as the outer retina the behavior of cones is modulated by rod activity. Rod and cone signals are modulated by dopamine. Gain between photoreceptors and second order cells is modulated by lateral interactions of unknown path, pharmacology and mechanism. At the inner retina transmission from bipolar to third order cells is modulated by feedback to bipolar cells via unknown pharmacological and functional mechanisms. The technique of patch recording and simultaneous staining in retinal slices provides for the first time a means for defining pathways, determining pharmacology, characterizing receptors, and testing second messenger systems, so that the neuromodulatory pathways can be defined. Synaptic currents can be measured, elicited by puffs of transmitter substances or transretinal current, activating specific synaptic accessible in the slice. Cell membranes can be polarized by steps of voltage in the presence and absence of transmitters and modulators, while isolating their effects upon specific voltage-gated membrane currents. The effects of modulation of release can be measured by recording synaptic inputs from cells postsynaptic to the subject cell thus using the postsynaptic cell as a bioassay for release. The behavior of second messenger systems can be controlled by introducing modulators and blockers into the cytoplasm via the path electrode. With these techniques the source of modulatory signals, their pharmacology, the membrane receptors, the second messenger pathways, and the sites affected by the modulation can be defined. This work is of value in health science because it attempts to define some of the fundamental mechanisms underlying visual functions. Since much of the mechanism is mediated by pharmacology to be defined in these studies, the route for medical treatment will also be clarified. Thus it may be possible to provide a link between retinal function (or dysfunction) and pharmacological intervention.
Showing the most recent 10 out of 33 publications
