The entorhinal cortex (EC) and the hippocampus are two deeply intertwined brain regions located within the medial temporal lobe, forming a circuit fundamental to higher-level cognition. The EC serves as the principal gateway for processed sensory information to enter the hippocampus, which then processes and consolidates this data into storable memories. Understanding their relationship involves examining their anatomical placement, the specific neural wiring that connects them, and the collaborative functions that emerge from their interaction.
Locating the Structures: Anatomy of the EC and Hippocampus
Both the entorhinal cortex and the hippocampus are nestled deep within the temporal lobe. The hippocampus, which gets its name from the Greek word for seahorse due to its curved shape, is a C-shaped structure essential for memory formation. It is part of a larger unit called the hippocampal formation, which also includes the dentate gyrus and the subiculum.
The entorhinal cortex is a portion of the parahippocampal gyrus, positioned immediately adjacent to the hippocampus. This location makes the EC the primary interface between the neocortex and the hippocampus. The EC acts as a funnel, gathering highly processed multimodal sensory information before sending it onward. The EC itself is often divided into medial and lateral regions, which handle different types of information before relaying it to the hippocampus.
The Information Superhighway: The Perforant Pathway
The physical connection that links the entorhinal cortex to the hippocampus is called the perforant pathway. This pathway is the main source of input to the hippocampus, making it one of the most significant neural connections in the brain’s memory circuitry. The flow of information along this pathway is largely unidirectional, forming a defined sequence of processing steps within the hippocampal formation.
Information from the entorhinal cortex begins its journey in distinct layers of the EC, specifically layers II and III. Neurons in layer II primarily project to the dentate gyrus and the CA3 region of the hippocampus. The Dentate Gyrus then forwards this information to CA3 via mossy fibers, which subsequently projects to the CA1 region through connections known as Schaffer collaterals.
In parallel, neurons in layer III of the entorhinal cortex send a separate projection that bypasses the Dentate Gyrus and CA3, connecting directly to the CA1 region. This sequential flow through the Dentate Gyrus, CA3, and CA1 is known as the trisynaptic circuit. After the information is processed, the CA1 region then sends projections back out of the hippocampus, primarily to the deeper layers of the entorhinal cortex, completing the anatomical and functional loop.
Encoding Experience: Memory and Spatial Navigation
The coordinated activity between the entorhinal cortex and the hippocampus allows for the encoding of episodic memories—the recollections of specific events, places, and times. The hippocampus is recognized for its role in memory consolidation, the process of converting new, short-term memories into stable, long-term memories. The EC provides the processed sensory context required for the hippocampus to bind together the various elements of an experience.
Their joint function in spatial navigation is perhaps the most precisely understood aspect of this collaboration, involving two specialized types of neurons. Within the hippocampus, researchers discovered “Place Cells,” which are neurons that fire specifically when an animal is in a particular location in an environment. The combined activity of many place cells forms a comprehensive cognitive map of the surroundings.
The entorhinal cortex contributes to this map with “Grid Cells,” which provide the underlying coordinate system. Grid cells fire multiple times as an animal moves, creating a highly regular, repeating pattern of activity that tessellates the environment in a hexagonal lattice. This pattern functions like an internal GPS, allowing the brain to measure distances and directions traveled. The input from the EC’s grid cells is leveraged by the hippocampus to form the specific place fields.
Early Targets: Vulnerability in Neurodegenerative Disease
The interconnected nature of the entorhinal-hippocampal circuit makes it vulnerable to neurodegenerative disorders, particularly Alzheimer’s Disease (AD). The entorhinal cortex is frequently one of the first brain regions to show pathological changes, such as the accumulation of tau protein tangles, often before cognitive symptoms become apparent. This selective vulnerability in the EC is thought to be the starting point for the disease’s progression.
The degradation of the EC directly impacts the hippocampus because it cuts off the primary input of information via the perforant pathway. This disruption to the circuit explains why the earliest symptoms of Alzheimer’s Disease involve a deficit in short-term memory and episodic recall. As the disease spreads from the EC, it affects the neurons responsible for spatial mapping, leading to a breakdown of the grid cell and place cell systems. This degradation manifests clinically as spatial disorientation, where patients struggle to navigate familiar environments, a symptom that accompanies memory loss.