The limbic system includes the medial temporal lobe, including the hippocampus, subiculum, parahippocampal gyrus, uncus, the mammillary body, hypothalamus, stria terminalis, septum, and cingulate gyrus, and it is involved in human instinct and homeostasis. The limbic system forms a closed circuit connecting these areas, called the circuit of Papez, in which the hippocampus plays a key role.
A variety of information is input from the association area, thalamus, amygdala, and claustrum into the entorhinal cortex of the medial temporal lobe. The entorhinal cortex has two hippocampal projection pathways. One is called the alvear pathway that projects into Ammon’s horn (CA1); however, it is not fully understood. The other is called the perforant pathway, which reaches the hippocampus by penetrating the subiculum. Most fibers of the perforant pathway enter the hippocampus, reach the molecular layer of the dentate gyrus, and project to the dendrites of granule cells, which are neurons within the dentate gyrus. This is input from outside the hippocampus into the hippocampus.
After projections from the perforant pathway are received by granule cell dendrites of the dentate gyrus, granule cell axons (mossy fibers) project to dendrites of neurons in the CA4 and CA3 areas of the polymorphic layer of the dentate hilus. These mossy fibers are glutamatergic, excitatory, and rich in zinc. Axons of CA3 neurons that receive most mossy fiber projections then project to dendrites within Ammon’s horn (CA1); these fibers are called Schaffer collaterals. CA1 axons of Ammon’s horn project to neurons in the subiculum of the hippocampus, which in turn project out of the hippocampus.
Fibers projected out of the hippocampus pass through the fimbria and fornix to reach the anterior thalamic nucleus and are subsequently input into the mammillary body from the mammillothalamic tract. Fibers connect to the anterior thalamic nucleus and cingulate gyrus of the frontal lobe.