What Are Current Concepts on the Functional Organization of the Locus Coeruleus and Its Role in Cognition and Neurodegeneration?
Eduardo E. Benarroch
Abstract
The locus coeruleus noradrenergic (LC-NE) system provides a widespread innervation to the CNS. Through both targeted and diffuse projections, this system has a major role in the control of arousal, attention, working memory, sensory processing, episodic and emotional memory, responses to stress, and goal-directed motivated behavior.1-10 Recent studies, primarily in rodents, have provided new insights into the organization and function of the LC-NE system, emphasizing its anatomical and functional heterogeneity and distinct modes of operation (Figure).11 Subpopulations of LC-NE neurons can modulate specific cognitive processes through distinct connections with forebrain areas.12-14 In addition, LC-NE neurons may fire in synchrony and, through axon collaterals to multiple brain areas, provide for a state-dependent global modulation of behavioral states, such as the sleep-wake cycle.15 Furthermore, the LC-NE system influences glial cells and microvasculature, thereby exerting metabolic and neuroprotective effects.16,17 These new findings are of clinical relevance because the LC shows pathologic changes at early stages of neurodegenerative diseases, including the Alzheimer disease (AD)18,19 and Parkinson disease (PD).19,20 Neuroimaging techniques such as neuromelanin-sensitive MRI sequences to visualize LC cell bodies and PET tracers to assess NE transporter density in NE terminals are increasingly applied to assess the functional connectivity of the LC-NE system during normal cognition21-23 and its involvement in several neurodegenerative disorders.24-26 The focus of this brief review is to emphasize some of the new insights provided by these extensive basic, neuropathologic, and imaging studies.