Evidence is presented which indicates that experience- independent modifications of functional circuitry in the visual cortex are regulated by extrahalamic afferent systems that use acetylcholine (ACh) and norepinephrine (NE) as transmitters. The presence of either ACh or NE appears sufficient to permit the ocular dominance (OD) changes that occur in kitten cortex after brief periods of monocular deprivation (MD) because destruction of both system is required to produced a reliable deficit in ocular dominance plasticity. Five experiments are proposed which will use anatomical, pharmacological and neurophysiological methods to characterize the individual and combined role of ACh and NE in modulating developmental plasticity in visual cortex. The first project will address the issue of whether destruction of the cholinergic and noradrenergic systems prevents ocular dominance changes after long-term MD. The second project is designed to determine whether the anatomical consequences of long-term MD, such as the shrinkage of neurons in the deprived lateral geniculate lamina and changes in the widths of OD columns in cortical layer IV, are prevented if cortical ACh and NE are depleted. In projects 3 and 4 I propose to use the minipump infusion method to establish which of the NE and ACh receptor types mediate the effects relevant to synaptic plasticity. The final project again will use the minipump infusion method in an attempt to restore some susceptibility to MD in adult animals by applying substances that will potentiate endogenously released ACh. These experiments should help to define the possible mechanisms by which activity-dependent synaptic modifications are regulated in the visual cortex.
