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Abstract:
The locus coeruleus (LC) neuromodulates the limbic system through direct projections to the hippocampal formation (HF) and amygdala (Amy) (Morgane et al. 2005 Prog Neurobiol 75:143-60). HF and Amy could in turn regulate noradrenergic activity necessary for memory processes (McIntyre et al. 2012 Neurosci Biobehav Rev 36:1750-62). Here, we examined whether such regulation could be substantiated by direct monosynaptic projections from HF and Amy to LC. We analyzed the distribution of anterograde labeling produced in LC in macaque monkeys with injections of biotin-dextran amine or Phaseolus vulgaris leucoagglutinin in the entorhinal cortex (EC), Ammon horn (CA1-3), dentate gyrus (DG), and subiculum (Sub), as well as in different nuclei of the amygdala, baring the central nucleus which was previously shown to project to LC (Price Amaral 1981 J Nsci 1:1242-59). Within HF, injections in Sub resulted in the highest number of labeled terminals in LC, particularly throughout the entire rostrocaudal extent of the lateral portion of the nucleus. Injections placed in EC produced labeling only in cases where Amy was also involved. However, different labeling patterns were obtained in LC after injections in the same amygdala nuclei with contamination of different EC fields. Injections in CA1-3 or DG did not label LC. Within the amygdala, only injections made in the basal magnocellular nucleus (Bmc) and in the paralaminar nucleus (PL) produced labeling in the lateral portion of LC, similar to the labeling produced with injections in Sub. Prior studies showed that both Sub and basal Amy receive projections from LC; the present study suggests that these projections are bidirectional in primates. Notably, whereas prior rodent studies proposed that basolateral amygdala regulates LC indirectly through CeA (Bouret et al. 2003 J Neurosci 23:3491-7), the present tracing data indicates that the primate Bmc can directly regulate LC. Although it is unclear whether the converging hippocampo- and amygdalo-coerulean projections identified here are functionally related, prior evidence from animal and human studies suggests that both could have a role in memory. The subicular projection to LC offers an ideal substrate for the hippocampal regulation of forebrain noradrenergic activity necessary for memory retrieval (Eldridge et al. 2005 J Nsci 25:3280-6; Sara 2010 Front Behav Nsci 4: 1-5). Accordingly, the direct projections from Bmc to LC could contribute in restoring central arousal states that promote emotional memory consolidation (Sterpenich et al. 2006 J Neursci 26:7416-23). Supported by the Max Planck Society and the Center for Integrative Neuroscience.
