Connectivity between the central nucleus of the amygdala and the bed nucleus of the stria terminalis in the non-human primate: neuronal tract tracing and developmental neuroimaging studies.

The lateral division of the bed nucleus of the stria terminalis (BSTL) and central nucleus of the amygdala (Ce) form the two poles of the 'central extended amygdala', a theorized subcortical macrostructure important in threat-related processing. Our previous work in nonhuman primates, and humans, demonstrating strong resting fMRI connectivity between the Ce and BSTL regions, provides evidence for the integrated activity of these structures. To further understand the anatomical substrates that underlie this coordinated function, and to investigate the integrity of the central extended amygdala early in life, we examined the intrinsic connectivity between the Ce and BSTL in non-human primates using ex vivo neuronal tract tracing, and in vivo diffusion-weighted imaging and resting fMRI techniques. The tracing studies revealed that BSTL receives strong input from Ce; however, the reciprocal pathway is less robust, implying that the primate Ce is a major modulator of BSTL function. The sublenticular extended amygdala (SLEAc) is strongly and reciprocally connected to both Ce and BSTL, potentially allowing the SLEAc to modulate information flow between the two structures. Longitudinal early-life structural imaging in a separate cohort of monkeys revealed that extended amygdala white matter pathways are in place as early as 3 weeks of age. Interestingly, resting functional connectivity between Ce and BSTL regions increases in coherence from 3 to 7 weeks of age. Taken together, these findings demonstrate a time period during which information flow between Ce and BSTL undergoes postnatal developmental changes likely via direct Ce → BSTL and/or Ce ↔ SLEAc ↔ BSTL projections.
Competing Interests: Dr. Kalin has received honoraria from CME Outfitters, Elsevier, and the Pritzker Neuropsychiatric Disorders Research Consortium. He is on the Advisory Boards for Corcept Therapeutics and Skyland Trail - George West Mental Health Foundation. Dr. Kalin is a Stockholder in Corcept Therapeutics, and owns several patents including: promoter sequences for corticotropin-releasing factor alpha (U.S. Patent #7071323, issued on 07-04-06); a method of identifying agents that alter the activity of the promoter sequences (U.S. Patent #7531356 issued on 05-12-09); promoter sequences for urocortin II and the use thereof (U.S. Patent #7087385 issued on 08-08-06); and promoter sequences for corticotropin-releasing factor binding protein and use thereof (U.S. Patent #7122650, issued on 10-17-06). All other authors declare no conflicts of interest.