perforant

Perforant pathway, also known as the perforant fiber pathway, is a major input to the hippocampal formation from the entorhinal cortex. It consists of axons that originate primarily in the entorhinal cortex and project to the dentate gyrus and, to a lesser extent, to CA3. The pathway is traditionally divided into two components: the medial perforant path (MPP) arising from the medial entorhinal cortex and the lateral perforant path (LPP) arising from the lateral entorhinal cortex. These fibers travel to the hippocampus and terminate in the molecular layers of the dentate gyrus—MPP in the middle molecular layer and LPP in the outer molecular layer—where they synapse with the dendrites of dentate granule cells.

The perforant pathway provides the major direct cortical input to the hippocampus, forming part of the trisynaptic circuit that also includes the mossy fiber projection from dentate granule cells to CA3 and the Schaffer collateral projection from CA3 to CA1. In addition to the perforant projections, entorhinal cortex layer III neurons contribute to a related input to CA1 via the temporoammonic pathway.

Functions and significance: The perforant pathway is essential for the encoding and retrieval of episodic memory and spatial navigation, supporting synaptic plasticity mechanisms such as long-term potentiation within the hippocampal network. Developmentally, the pathway forms during prenatal and early postnatal life and becomes a key conduit for information entering the hippocampus.

Clinical relevance: Early degeneration of the entorhinal cortex and perforant pathway is observed in Alzheimer’s disease and is associated with memory impairment. Disruption of this pathway in animal models impairs learning and memory tasks.