The visual areas of the cerebral cortex of humans and other mammals are known to be highly susceptible to environmental factors during critical periods of postnatal development. Thus, various types of peripheral insult such as unequal binocular vision due to ptosis, congenital cataracts, unequal ammetropia or strabismus in addition to traumatic injury or eye infection during postnatal development can lead to permanent deficits in cortical processing of retinal output. The adult visual cortex was thought to be less susceptible to peripheral effects and less able to functionally reorganize in an adaptive way. However, recent evidence suggests that the adult visual cortex is capable of functional reorganization--both transient and permanent. A recently discovered molecule, nitric oxide (NO), that is made by neurons in the adult visual cortex, has been suggested to play a role in modulating the efficiency of chemical synaptic communication. We have previously demonstrated that up-regulation of the brain's endogenous NO-synthesis in the adult feline primary visual cortex amplifies the visual responses and enhances signal detection by individual neurons in response to suprathreshold visual stimuli presented monocularly. However, the effects of NO on binocular integration and threshold sensitivity are not known. Moreover, nothing is known regarding the potential capacity for NO to modulate response in monocularly visually derived animals (a model for amblyopia in human). Thus, we plan to investigate in quantitative fashion, the effects of endogenously synthesized NO on monocular contrast response functions, contrast threshold, response reliability, and binocular integration by individual neurons in the normal adult and amblyoptic monocularly deprived cat. To accomplish this, we will drifting randomly, interleaved sine-wave grating stimuli in conjunction with multi-barrel iontophoresis of endogenous NO up-and/or down-regulating compounds and extracellular single-unit recording to locally modify the NO environment in cortex while evaluating cells' visual responses. We will also utilize a new family of fluorescent dyes that detect NO production from neurons in vitro to characterize their functional properties and anatomical relationship to ocular dominance column (in normal adult cats and rats and monocularly visually deprived cats), in vitro.
