Distribution and overlap of entorhinal, premotor, and amygdalar connections in the monkey anterior cingulate cortex

J Comp Neurol. 2021 Mar;529(4):885-904. doi: 10.1002/cne.24986. Epub 2020 Aug 13.


The anterior cingulate cortex (ACC) is important for decision-making as it integrates motor plans with affective and contextual limbic information. Disruptions in these networks have been observed in depression, bipolar disorder, and post-traumatic stress disorder. Yet, overlap of limbic and motor connections within subdivisions of the ACC is not well understood. Hence, we administered a combination of retrograde and anterograde tracers into structures important for contextual memories (entorhinal cortex), affective processing (amygdala), and motor planning (dorsal premotor cortex) to assess overlap of labeled projection neurons from (outputs) and axon terminals to (inputs) the ACC of adult rhesus monkeys (Macaca mulatta). Our data show that entorhinal and dorsal premotor cortical (dPMC) connections are segregated across ventral (A25, A24a) and dorsal (A24b,c) subregions of the ACC, while amygdalar connections are more evenly distributed across subregions. Among all areas, the rostral ACC (A32) had the lowest relative density of connections with all three regions. In the ventral ACC, entorhinal and amygdalar connections strongly overlap across all layers, especially in A25. In the dorsal ACC, outputs to dPMC and the amygdala strongly overlap in deep layers. However, dPMC input to the dorsal ACC was densest in deep layers, while amygdalar inputs predominantly localized in upper layers. These connection patterns are consistent with diverse roles of the dorsal ACC in motor evaluation and the ventral ACC in affective and contextual memory. Further, distinct laminar circuits suggest unique interactions within specific ACC compartments that are likely important for the temporal integration of motor and limbic information during flexible goal-directed behavior.

Keywords: RRID: AB_2340397; RRID: SCR_002526; RRID:AB_221558; RRID:AB_221561; RRID:AB_2313606; RRID:AB_2336382; RRID:AB_2336819; RRID:AB_2536192; RRID:AB_2536196; RRID:SCR_000432; RRID:SCR_001622; RRID:SCR_002465; dorsal premotor cortex; medial prefrontal cortex; medial temporal; non-human primate; tract-tracing.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amygdala / anatomy & histology*
  • Amygdala / chemistry
  • Amygdala / cytology
  • Animals
  • Entorhinal Cortex / anatomy & histology*
  • Entorhinal Cortex / chemistry
  • Entorhinal Cortex / cytology
  • Female
  • Gyrus Cinguli / anatomy & histology*
  • Gyrus Cinguli / chemistry
  • Gyrus Cinguli / cytology
  • Macaca mulatta
  • Male
  • Neural Pathways / anatomy & histology
  • Neural Pathways / chemistry
  • Neural Pathways / cytology
  • Prefrontal Cortex / anatomy & histology*
  • Prefrontal Cortex / chemistry
  • Prefrontal Cortex / cytology