Extrathalamic modulation of cortical function.

Abstract : The goal of the proposed studies is to characterize the effects of noradrenergic (NA) afferents on cortical information processing. our previous studies indicate that the primate locus coeruleus (LC) system, originating in the pontine brainstem, innervates neocortex more densely than previously thought, exhibiting highly specific patterns in terms of the regional and laminar distribution of its axons. our previous neurophysiological observations suggest that this system imposes state-related modulatory effects on thalamo- cortical and cortico-cortical systems. The proposed studies have the following Specific Aims: (1) To examine, in monkeys, the effects of manipulating the LC-NA system on ERPs, EEG characteristics, and associated behaviors in operant paradigms that utilize visual or auditory cues; (2) To correlate the activities of individual monkey LC-NA neurons with cortical neuronal activity and the measures utilized in Aim 1; (3) To extend our preliminary observation that activation of the LC by local drug infusion, in halothane-anesthetized rats, produces EEG signs of cortical and hippocampal activation; (4) To examine the relationship between the intensity of LC neuronal activity and rates of norepinephrine release in neocortex and hippocampus by performing microdialysis in these forebrain terminal regions in anesthetized rats during manipulation of LC activity.

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