Unlocking the Brain's GPS: How Comparative Anatomy Illuminates the Hippocampus
"Exploring the evolutionary journey of the hippocampus, from reptiles to mammals, and what it means for understanding memory and spatial navigation."
What can we learn by comparing the brains of different animals, particularly when it comes to a structure as crucial as the hippocampus? This question isn't as straightforward as it seems. It depends on what we hope to achieve through such comparisons and, fundamentally, what we consider to be the hippocampus in the first place.
In this article, we will delve into the essential considerations for conducting meaningful comparative studies of the hippocampus. To make valid comparisons, we need a clear definition of what constitutes the hippocampus, including its subdivisions and the relevant circuitry levels. As we will see, defining these elements, as well as the level of biological classification (species, family, order), depends heavily on the available data.
We'll adopt a pragmatic approach, focusing on available data relevant to our narrative and emphasizing connectivity patterns as a powerful tool for proposing potential homologies in the hippocampus across species. Consider this a companion piece emphasizing the 'wiring' that defines this essential brain structure.
Comparative Evidence
A 2025 study, "Traces of phylogeny and ecology in hippocampal neuron numbers," assembled an extensive dataset covering five interconnected hippocampal neuron populations across a large number of mammalian species. The study used design-based stereology to quantify these populations. This approach helps connect hippocampal structure with phylogeny and ecological variation.
Methods and Limits
Comparative hippocampal research commonly combines anatomical, physiological, cellular, and molecular approaches to examine similarities and differences across species. These methods can clarify shared organizational principles, but comparisons must be interpreted cautiously because species differ in brain structure, behavior, and evolutionary history. As a result, anatomical resemblance alone does not establish identical function.
From Structure to Function
The hippocampus is a major brain component in humans and many other vertebrates. In humans, the hippocampus, dentate gyrus, and subiculum form components of the hippocampal formation within the limbic system. The structure is located in the medial temporal lobe of each cerebral hemisphere. Comparative work continues to examine how hippocampal patterns emerged at the species level, although the evolutionary mechanisms behind those patterns remain unclear.
What Exactly Is the Hippocampus? A Matter of Definition
The term 'hippocampus,' first coined to describe a structure in the mammalian brain resembling a seahorse, has become synonymous with memory and spatial navigation. But how do we identify the 'hippocampus' in animals with vastly different brain structures? In mammals, the hippocampus includes the dentate gyrus, cornu ammonis (CA) fields (CA1, CA2, and CA3), and the subiculum. It's a three-layered cortex, each layer with distinct cellular compositions.
- The Fornix: Historically seen as the main output pathway, connecting the hippocampus to subcortical structures like the septal complex and mammillary bodies.
- The Entorhinal Cortex (EC): The primary cortical input to the hippocampus via the perforant pathway.
- The Trisynaptic Circuit: A traditional model emphasizing a specific pathway: EC to dentate gyrus, dentate gyrus to CA3, and CA3 to CA1. Recent views propose a greater emphasis on EC layer III projections and CA1/subiculum reciprocal connections.
Research in Motion
Recent hippocampal research is increasingly examining how molecular, cellular, and anatomical organization vary across species. Current reviews and studies suggest that understanding the hippocampus requires attention to both its subregions and its diverse cell types. This work is broadening the field beyond a single, uniform model of hippocampal function.
Limits of Direct Comparison
Comparative neuroanatomy compares brain structure and function across species, including humans and non-human primates, using tools such as diffusion MRI and quantitative MRI. Yet direct equivalence can be misleading: mammalian and reptilian brains may contain homologues of the neocortex and hippocampus without being organized identically. The hippocampus also includes specialized cell types, such as the mossy cell, that are not found in other cortical areas.
Defining the Hippocampus Across Vertebrates
Comparative studies have produced increasingly precise accounts of the anatomical, physiological, and biochemical properties of hippocampal subfields and their interconnections. One major approach is to ask whether connections can help define the hippocampus across vertebrates. This question has been explored particularly in mammals, reptiles, and birds, alongside newer molecular and cellular analyses of hippocampal subregions and cell types.
The Big Picture: Why Hippocampal Comparisons Matter
By comparing the hippocampus across different species, we can gain valuable insights into the evolution of memory, spatial navigation, and related cognitive functions. For all mammalian species studied, the hippocampus receives key cortical inputs from the entorhinal cortex, organized in a consistent manner. However, in reptiles and birds, the picture is less clear.
Individual Differences
Current expert discussion is moving toward accounts of hippocampal function that include differences between individuals. A 2026 Nature Reviews Neuroscience opinion considers how an existing paradigm might be developed to capture the essence of interindividual differences in brain function. This perspective suggests that a complete account of the hippocampus should not treat variation between people as incidental.
Next Directions
Future comparative research may integrate anatomical, physiological, molecular, and cellular evidence more systematically. It may also compare a wider range of vertebrates while distinguishing shared organization from lineage-specific specialization. Such work could clarify how hippocampal structure relates to memory, cognition, learning, and ecological demands.
Evidence Across Levels
Comparative neuroanatomy is an evolutionary research program that depends on integrating multiple lines of evidence. Scholarship in this area has been shaped by researchers including Lisa Stefanacci and Gary van Hoesen. At the same time, the hippocampus must be understood in relation to both spatial processing and its broader, acknowledged role in memory. This creates a systemic challenge: linking specialized spatial functions to wider cognitive processes.
Why the Hippocampus Matters
The hippocampus is relevant to human memory, cognition, and learning, making comparative research more than an exercise in cataloging brain structures. Comparisons across species can help researchers identify which features are broadly shared and which are specialized. However, translating findings across species requires care because anatomical similarity does not guarantee identical human experience or function.
While genetically defined areas homologous to the lateral and medial entorhinal cortex might exist in these groups, data on their connectivity is limited. Further research is needed to fully understand the similarities and differences in hippocampal organization across the animal kingdom.
Ultimately, comparative studies of the hippocampus can reveal fundamental principles about brain structure, function, and evolution, shedding light on the neural basis of cognition and behavior.