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In the brain, the perforant pathway provides a connectional route from the entorhinal cortex to all fields of the hippocampal formation, including the dentate gyrus, all CA fields (including CA1), and the subiculum.
Though it arises mainly from entorhinal layers II and III, it comprises a smaller component that originates in deep layers V and VI. There is a major dichotomy with respect to the laminar origin and related terminal distribution: neurons in layer II (and possibly layer VI) project to the dentate gyrus and CA3, whereas layer III (and possibly layer V) cells project to CA1 and the subiculum.
It may play a role in temporal lobe seizures.
In rats, pyramidal and stellate cells in layer II of entorhinal cortex project through the subiculum of the hippocampus, giving rise to the name "perforant pathway". These glutamatergic fibers form a laminar pattern and terminate in the dentate gyrus and cornu ammonis 3 (CA3) region of the hippocampus. Fibers arising in the lateral portions of the entorhinal cortex show enkephalin immunoreactivity, whereas medial portions appear to contain cholecystokinin. Additionally, pyramidal cells in layer III of the entorhinal cortex send topographic projections along the perforant pathway which branch into the subiculum and CA1.
In mice, the projection to CA3, CA1, and the subiculum all come primarily from EC layer III.
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