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. Investigations from our laboratory as well as others have shown that local administration of norepinephrine (NE) can increase the magnitude of individual sensory neuron responses to synaptic stimuli. Collectively these findings have prompted the suggestion that output from the LC plays an important role in facilitating the transfer of sensory information through neural circuits according to changing behavioral contingencies. However, many questions remain concerning the precise way in which output from the LC impacts on the stimulus coding properties of single cells and ultimately how NE release influences the operation of ensembles of neurons engaged in common sensory functions. In addition there has recently been considerable interest in galanin, a neuroactive peptide which co-localizes with NE in sub-populations of LC neurons. Despite the potential for co-release of galanin at noradrenergic synapses there have been almost no studies to characterize its actions on cells in LC innervated circuits. Our fundamental hypothesis is that the LC efferent system regulates signal transmission along sensory pathways via: 1) anatomically and neurochemically specific efferent projections and 2) physiologically selective influences on response properties of individual neurons in sensory circuits. In order to test these ideas the current proposal establishes 3 major goals: 1) determine the organization of galaninergic projections from LC to the ascending trigeminal somatosensory pathway in rat, 2) determine the individual and combined effects of putative LC transmitters/modulators on intrinsic membrane and cellular response properties of identified neurons in rat barrel field cortex and 3) determine the effects of phasic vs tonic activation of LC on response threshold and receptive field properties of rat barrel field cortical neurons. The studies will involve retrograde tract tracing, immunohistochemistry, extra- and intracellular recording from single neurons in anesthetized animals and tissue slice preparations, electrical and chemical activation 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 clarify how the LC efferent system influences sensory stimulus coding properties of sensory neurons, but will also provide a foundation for predicting how sensory circuits would perform under behavior conditions where output from the LC is fluctuating. As such these studies will provide a much needed link between cellular/membrane studies of LC-NE attributes and the proposed role of the LC efferent system in regulating perceptual processes across behavioral states.
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