title: Specialized pathways from the primate amygdala to posterior orbitofrontal cortex.
abstract: The primate amygdala sends dense projections to posterior orbitofrontal cortex (pOFC) in pathways that are critical for processing emotional content, but the synaptic mechanisms are not understood. We addressed this issue by investigating pathways in rhesus monkeys (Macaca mulatta) from the amygdala to pOFC at the level of the system and synapse. Terminations from the amygdala were denser and larger in pOFC compared with the anterior cingulate cortex, which is also strongly connected with the amygdala. Axons from the amygdala terminated most densely in the upper layers of pOFC through large terminals. Most of these terminals innervated spines of presumed excitatory neurons and many were frequently multisynaptic and perforated, suggesting high synaptic efficacy. These amygdalar synapses in pOFC exceeded in size and specialization even thalamocortical terminals from the prefrontal-related thalamic mediodorsal nucleus to the middle cortical layers, which are thought to be highly efficient drivers of cortical neurons. Pathway terminals in the upper layers impinge on the apical dendrites of neurons in other layers, suggesting that the robust amygdalar projections may also activate neurons in layer 5 that project back to the amygdala and beyond to autonomic structures. Among inhibitory neurons, the amygdalar pathway innervated preferentially the neurochemical classes of calbindin and calretinin neurons in the upper layers of pOFC, which are synaptically suited to suppress noise and enhance signals. These features provide a circuit mechanism for flexibly shifting focus and adjusting emotional drive in processes disrupted in psychiatric disorders, such as phobias and obsessive-compulsive disorder.
authors.affiliation: Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts 02118, and.
authors.forename: Clare
authors.initials: C
authors.lastname: Timbie
authors.affiliation: Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts 02118, and Department of Health Sciences, Boston University, Boston, Massachusetts 02215 barbas@bu.edu.
authors.forename: Helen
authors.initials: H
authors.lastname: Barbas
mesh_terms: D000344:Afferent Pathways / Q000502:physiology*; D000679:Amygdala / Q000166:cytology / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D000704:Analysis of Variance; D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003911:Dextrans / Q000378:metabolism; D005260:Female; D007546:Isoquinolines / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D020645:Mediodorsal Thalamic Nucleus / Q000502:physiology; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D008959:Models, Neurological; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D017397:Prefrontal Cortex / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D002135:Calcium-Binding Proteins; D003911:Dextrans; D007546:Isoquinolines; C076397:biotinylated dextran amine; D001710:Biotin; C017475:lucifer yellow
keywords: OCD; emotion and amygdala; neural circuits; orbitofrontal; synapse; thalamus