Revisiting the hippocampal-amygdala pathway in primates: association with immature-appearing neurons

Neuroscience. 2012 Jun 14;212:104-19. doi: 10.1016/j.neuroscience.2012.03.040. Epub 2012 Apr 19.


Elucidation of the 'fear circuit' has opened exciting avenues for understanding and treating human anxiety disorders. However, the translation of rodent to human studies, and vice versa, depends on understanding the homology in relevant circuits across species. Although abundant evidence indicates that the hippocampal-amygdala circuit mediates contextual fear learning, previous studies indicate that this pathway is more restricted in primates than in rodents. Moreover, cellular components of the amygdala differ across species. The paralaminar nucleus (PL) of the amygdala, a structure that is closely associated with the basal nucleus, is one example, having no clear homologue in rodents. In both human and nonhuman primates, the PL contains a subpopulation of immature-appearing neurons, which merge into the corticoamygdaloid transition area (CTA). To understand whether immature-appearing neurons are positioned to participate in fear circuitry, we first mapped the hippocampal-amygdala projection in the monkey. We then determined whether immature-appearing neurons were targets of this path. Retrograde results show that the hippocampal inputs to the amygdala originate in uncal region (CA1') and the rostral prosubiculum, consistent with earlier studies. The amygdalohippocampal area, ventral basal nucleus, the medial paralaminar nucleus, and its confluence with the CTA are the main targets of this projection. Immature neurons are prominent in the PL and CTA, and are overlapped by anterogradely labeled fibers from CA1', particularly in the medial PL and CTA. Hippocampal inputs to the amygdala are more focused in higher primates compared to rodents, supporting previous anatomic studies and recent data from human functional imaging studies of contextual fear. At the cellular level, a hippocampal interaction with immature neurons in the amygdala suggests a novel substrate for cellular plasticity, with implications for mechanisms underlying contextual learning and emotional memory processes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / cytology*
  • Amygdala / physiology
  • Animals
  • Cell Differentiation / physiology*
  • Hippocampus / cytology*
  • Hippocampus / physiology
  • Macaca fascicularis
  • Macaca nemestrina
  • Neural Pathways / cytology
  • Neural Pathways / physiology
  • Neural Stem Cells / physiology
  • Neurogenesis / physiology*
  • Neuronal Plasticity / physiology*
  • Neurons / cytology*
  • Neurons / physiology