Inhibitory Neurons in Human Anterior Entorhinal Cortex and Some Comparisons With the Rhesus Monkey

The primate anterior entorhinal cortex (EC) receives rich projections from the amygdala and from multimodal association areas, including the medial prefrontal, anterior cingulate, and orbitofrontal cortices. Axon terminations from these structures on the anterior EC facilitate processing of the emotional aspects of stimuli and events. The EC projects to hippocampus, which is associated with episodic memory. Processing in the anterior EC is modulated by inhibitory neurons, which in primates express the calcium-binding proteins (CBPs): calretinin (CR), or calbindin (CB) or parvalbumin (PV), which collectively account for most inhibitory neurons in the primate cortex. Here, stereological analysis of these neurochemical classes of inhibitory neurons in the anterior half of EC in humans revealed similar patterns as in rhesus monkeys. In both primate species, the densest neuronal subpopulation of presumed inhibitory neurons expressed CR, followed by CB, and lastly by PV. In both species CR neurons were most prevalent in layers I and II, CB neurons in layers II and III and PV neurons in the middle-deep layers. Moreover, the medial and lateral sectors of the anterior EC had different densities of neurons expressing these CBPs. Further analysis revealed that in the human anterior EC, virtually all PV neurons expressed the GABAergic marker GAD67/GAD1 (glutamate decarboxylase 67/glutamate decarboxylase 1), whereas only two-thirds of CB neurons and only one-third of CR neurons colocalized with GAD67/GAD1. In the entire neuronal population of the anterior half of human EC estimated by stereology, 10% expressed GAD67/GAD1, comparable to the collective population of CBP-positive neurons that colocalized with GAD67/GAD1. These findings reveal that the medial and lateral sectors of anterior EC have distinct inhibitory microenvironments, which likely affect the processing of input and output of hippocampus.