The entorhinal cortex (EC) is a multi-layered region of the brain that operates as a central processing hub for information related to memory and navigation. This structure is positioned strategically within the brain’s circuitry, serving as the primary interface between the neocortex—the large, outer layer of the brain responsible for higher-level thought—and the hippocampus, a structure recognized for its role in forming new memories. Understanding the entorhinal cortex’s geography and its unique cellular functions offers insight into how the brain manages our sense of self in space and time. This area is a significant component in the system that allows us to recall personal events and find our way around the world.
Precise Anatomical Geography
The entorhinal cortex is situated deep within the brain in the medial temporal lobe, which lies beneath the temples on either side of the head. It forms the anterior portion of the parahippocampal gyrus, a strip of tissue that wraps around the hippocampus. This placement makes the entorhinal cortex a part of the extended hippocampal formation, a group of interconnected structures that work together on memory and spatial processing.
The structural arrangement of the entorhinal cortex is characterized by a six-layered organization. A distinguishing trait is the lamina dissecans, a layer that lacks cell bodies where the fourth layer would normally be found. This anatomical feature divides the cortex into superficial layers (Layers II and III) and deep layers (Layers V and VI). The entorhinal cortex is bordered by the rhinal sulcus laterally and is adjacent to the amygdala and hippocampus dorsomedially.
The Gateway to the Hippocampus
The entorhinal cortex functions as the primary gateway through which processed sensory and cognitive information enters and exits the hippocampus. This relationship establishes the EC as a vital relay station for memory processing. The primary communication line between these two structures is the perforant path, a dense bundle of nerve fibers.
The perforant path originates mainly from the superficial layers of the entorhinal cortex (Layers II and III) and projects to various parts of the hippocampal formation. Neurons in Layer II project primarily to the dentate gyrus and the CA3 region. Conversely, neurons in Layer III project to the CA1 region and the subiculum. This separation of input ensures that different types of information are routed through specific hippocampal circuits for processing and consolidation. The integrity of this pathway is fundamental to the formation and retrieval of declarative memories.
Core Role in Spatial Memory and Navigation
The entorhinal cortex is crucial for spatial processing, often described as the brain’s internal Global Positioning System (GPS). This capability is attributed to specialized neurons called “grid cells,” discovered within the medial entorhinal cortex. Grid cells fire only when an individual is located in specific positions within an environment, forming a precise, hexagonal pattern of firing locations.
The collective activity of these grid cells creates a metric map of the environment, allowing the brain to compute location, distance, and direction as the body moves. This system provides a stable coordinate system independent of external landmarks. The grid cell network works alongside other specialized neurons in the medial entorhinal cortex, such as head direction cells and border cells, which provide directional and boundary information. These spatial signals are then transmitted via the perforant path to the hippocampus, where they are integrated with contextual details to form comprehensive spatial memories.
Early Indicator in Neurodegenerative Disease
The entorhinal cortex is one of the first brain regions to show damage in Alzheimer’s disease (AD). Pathological changes, including the accumulation of neurofibrillary tangles (tau protein), begin here before spreading to other areas of the brain. The earliest stages of AD pathology are characterized by the presence of these tau tangles within the EC.
This localized damage directly impacts the function of grid cells and other neurons responsible for spatial mapping and memory. One of the earliest signs of cognitive impairment in AD patients is a deficit in spatial navigation, such as difficulty following familiar routes or getting lost. Furthermore, the breakdown of the perforant path—the connection between the EC and the hippocampus—destroys the communication link necessary for forming new memories. The vulnerability of this region makes the entorhinal cortex a focus for early diagnosis, as structural atrophy and functional disturbances are detectable years before severe memory loss occurs.