Many neuroanatomical studies have demonstrated that sensory areas of the mammalian brain receive a substantial noradrenergic innervation from the brainstem locus coeruleus (LC). Other work has shown that cells in the LC increase their tonic level of firing with arousal and discharge phasically in response to novel or behaviorally relevant sensory stimuli. These findings have prompted the suggestion that output from the LC plays an important role in regulating the transfer of sensory information through neural circuits according to changing behavioral contingencies. Many studies have used local methods of drug application to identity the cellular actions of exogenous norepinephrine (NE) in sensory circuits; however, there have been no detailed investigations to assess the impact of synaptically released NE on the signal processing capabilities of sensory pathways. Our fundamental hypothesis is that the LC-NE system regulates signal transmission along sensory pathways via anatomically specific efferent projections and physiologically selective influences on response properties of individual neurons in sensory circuits. In order to test this idea the current proposal establishes three major goals: 1) determine the organization of the LC efferent projection to target structures along the ascending somatosensory pathway in rat, 2) characterize the actions of NE on intrinsic and membrane response properties of morphologically and electrophysiologically identified sub- classes of neurons in rat """"""""barrel field"""""""" cortex and 3) determine the effects of both tonic and phasic modes of LC output on response threshold and receptive field properties of rat """"""""barrel field"""""""" cortical neurons. These studies will involve neuroanatomical tract tracing; extra- and intracellular recording from single neurons in anesthetized animals and in vitro tissue slice preparations, respectively; electrical and chemical stimulation of LC; mechanical stimulation of the mystacial vibrissae and computer based analysis of spike train data (in vivo studies) or membrane potential changes (in vitro studies). Completion of this work will not only clarity how the LC-NE system influences sensory stimulus coding properties of sensory neurons, but will also provide a foundation for predicting how sensory circuits would perform under behavioral conditions where output from the noradrenergic system is fluctuating. As such these studies will provide a much needed link between the cellular actions of NE and the proposed role of the noradrenergic system in regulating sensory responsiveness across behavioral states.
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