New perspectives on the functional organization and postsynaptic influences of the locus ceruleus efferent projection system.

Publisher Summary This chapter summarizes recent efforts on the design of anatomical and physiological experiments that are capable of bridging the gap between cellular-membrane studies of locus ceruleus-norepinephrine (LC-NE) attributes and more global hypotheses regarding the impact of the LC projection system on sensory neural network function. Recent studies using fluorescent retrograde tracers have shown that LC efferents to target structures along the trigeminal somatosensory pathway in rat exhibit an orderly projection with respect to the crossed trajectory of this ascending sensory system. It has been also found that LC projection neurons to somatosensory structures are organized into overlapping subsets within the nucleus, thus raising the possibility that a significant proportion of these cells may project to multiple, common somatosensory targets via axon collaterals. These studies show that the LC exhibits an internal organization and efferent projection pattern that is consistent with the idea that LC outputs can selectively and coordinately modulate the flow of somatosensory information through forebrain circuits. These findings indicate that NE can augment membrane responses to GABA via a β -receptor-linked/ cyclic adenosine monophosphate (cAMP) cascade of events. As such, these noradrenergic influences on putative transmitter-induced conductance changes are consistent with previously observed effects of iontophoretic NE on single-unit responses to GABA in anesthetized and awake, behaving animals. The results reported here continue to support and refine the idea that the LC efferent system exhibits a high degree of anatomical and physiological specificity with respect to its potential impact on target neuronal circuits. Overall, these advances in the understanding of the organizational principles and physiological specificity of the LC-NE efferent system provide new insights into the role of this monoamine-containing brain-stem nucleus in behavior.