Organization of noradrenergic efferents to arousal-related basal forebrain structures

Norepinephrine acts within select basal forebrain regions to modulate behavioral state and/or state-dependent processes, including the general regions encompassing the medial septal area, the medial preoptic area, and the substantia innominata. The present study examined the origin and organization of noradrenergic efferents to these basal forebrain regions by using combined immunohistochemical identification of noradrenergic neurons with retrograde tracing. Results indicate that the locus coeruleus provides the majority of noradrenergic input to these regions. Lesser, although at times substantial, contributions from the A1/C1 and A2/C2 adrenergic cell groups were also observed, particularly in the case of the medial preoptic region. Given the prominent state-modulating actions of the locus coeruleus, additional studies examined: 1) lateralization of locus coeruleus efferents to these regions; 2) the topographical organization of basal forebrain-projecting locus coeruleus neurons; and 3) the degree of collateralization of individual locus coeruleus neurons across these regions. Approximately 80-85% of locus coeruleus efferents to these regions project ipsilaterally. In general, basal forebrain-projecting neurons were distributed throughout the entire dorsoventral and rostrocaudal extent of the locus coeruleus. Additionally, a large proportion of locus coeruleus neurons project simultaneously to these basal forebrain terminal fields. Combined, these observations indicate coordinated actions of locus coeruleus neurons across these basal forebrain regions implicated in the regulation of behavioral state and/or state-dependent processes.