The studies proposed here are designed to elucidate the role played by noradrenergic (NA) afferents in neocortical information processing in primates. The NA projection to cortex originates in the locus coeruleus (LC) and innervates the entire neocortex. Our recent immunohistochemical studies indicate that this LC-NA innervation of monkey neocortex is regionally specific, highly organized, and more dense than previously thought. We have also described enhanced acoustic signal processing by monkey auditory cortex neurons during microiontophoresis of norepinephrine. These and other observations suggest an important role for NA input in determining the characteristics of stimuluselicited neocortical neuronal activity. To demonstrate a specific role for this innervation, multiple coordinated experiments are proposed. Microiontophoresis, LC stimulation, and transmitter-specific lesions will be combined with single-cell recording from neocortical sensory regions to determine the impact of the LC-NA system on cortical neuronal responses in unanesthetized monkeys. Histological reconstruction of recording sites will include immunohistochemical visualization of NA fibers to permit a direct comparison of the distribution of LC-NA effects on cortical neuronal activity with the distribution of afferent fibers. Data we have generated describing the activity of monkey LC neurons and the conduction properties of their axons will be used to make these experiments as physiologically relevant as possible. The impact of raphe-serotonergic input on cortical neuronal activity will also be investigated. These studies will yield: 1) detailed immunohistochemical maps of the NA and serotonergic innervation of specific cortical fields, 2) quantified measurements of the effects produced by iontophoretically applied putative neurotransmitters on functionally characterized neocortical neuronal activity, 3) comparable data on LC stimulation and lesion effects, 4) correlations between LC and neocortical neuronal activity, 5) a resulting hypothesis of the role of the LC-NA system in neocortical information processing.
