Specializations in amygdalar and hippocampal innervation of the primate nucleus accumbens shell.

The Nucleus accumbens (NAc) is critical to goal-directed behaviors as the main input structure for limbic pathways to the basal ganglia. The NAc shell is composed of inhibitory projection neurons that receive robust glutamatergic innervation from both the hippocampus and amygdala. In view of primate-specific changes in the neural composition of the NAc, it is still unclear how its circuits are organized in primates. We used a system-to-synapse approach to characterize amygdalar and hippocampal pathway distribution, innervation patterns, and synaptic characteristics in the NAc shell of rhesus monkeys (Macaca mulatta) of both sexes. Key findings showed that both the amygdalar and hippocampal pathways disproportionately innervated NAc shell interneurons relative to their population sizes, assessed via confocal systems' analysis and at the synaptic level with electron microscopy. The synaptic features associated with the two pathways were distinct. The amygdalar projection was denser, with larger boutons that more often contained mitochondria than the hippocampal projection. The hippocampal pathway had larger postsynaptic densities and more frequently formed perforated synapses, which are features associated with high synaptic efficacy. In addition, hippocampal boutons more frequently formed multiple synapses, often with one projection neuron and one interneuron. These interactions with the NAc shell suggest distinct mechanisms for the processing of affective signaling from the amygdala and contextual information from the hippocampus.Significance Statement The nucleus accumbens (NAc) is a key structure for motivated behavior; it receives dense pathways from the amygdala, associated with emotional significance, and the hippocampus, associated with context. In the NAc shell, both pathways disproportionately innervated interneurons, relative to their population size. The amygdalar boutons were somewhat larger and enriched with mitochondria, associated with sustained activity. Hippocampal terminations formed larger synapses and were more often multi-synaptic, suggesting high synaptic efficacy. These patterns diverge from previously described rodent circuit patterns. The findings suggest that internal emotional state and environmental cues related to context differentially affect circuits underlying goal-directed behavior in the NAc shell.