Topographic architecture of stress-related pathways targeting the noradrenergic locus coeruleus

Peripheral sympathetic nerves and brainstem noradrenergic neurons of the lo cus coeruleus (LC) respond in parallel to a variety of stress-related stimu li which results in norepinephrine release both peripherally and centrally. Elucidation of central pathways subserving modulation of LC neurons point to extranuclear noradrenergic dendrites of LC somata that extend into peri- coerulear areas as a major target of afferents that participate in behavior al and physiological responses to stress. Anterograde tract tracing combine d with immunoelectron microscopic detection of the catecholamine synthesizi ng enzyme tyrosine hydroxylase (TH) has demonstrated that the nucleus of th e solitary tract (NTS) and the ventrolateral aspect of the periaqueductal g ray (PAG), regions that participate in coordinating autonomic and motor beh avior in response to stress, preferentially target the rostral ventromedial aspect of the peri-LC. In contrast, limbic forebrain afferents including t he central nucleus of the amygdala (CNA) and the bed nucleus of the stria t erminalis (BNST), regions that coordinate emotional responses to external s tressors, provide direct synaptic input to noradrenergic dendrites that ext end into rostral dorsolateral peri-coerulear areas. Neurochemical identific ation of transmitter systems impinging on LC indicate that the CNA provides corticotropin-releasing factor (CRF), a peptide essential for integrated p hysiological responses to stress, to the dorsolateral LC. Endogenous opioid peptides that originate from medullary sources, however target primarily t he "core" of the LC. Our physiological data suggest that stress engages CRF and opioid afferents to the LC, which have opposing influences on this nor adrenergic system. The balance between opioid and CRF influences acting in the LC may, in part. maintain the balance of active and passive coping beha viors in response to stress. Understanding the afferent and neurochemical o rganization of the LC may help elucidate adaptations in neural circuits ass ociated with stress which impact on central noradrenergic function. (C) 200 1 Elsevier Science Inc. All rights reserved.