HIPPOCAMPUS: FUNCTIONS, ANATOMY AND PATHOLOGIES (WITH IMAGES) - NEUROPSYCHOLOGY - 2025

The hippocampus is a brain structure that is part of the limbic system and whose main functions are the formation of new memories - memory - and spatial orientation. It is located in the temporal lobe (one of the higher brain structures), but it is also part of the limbic system and is involved in functions of the lower structures.

Nowadays it is well documented that the main functions performed by the hippocampus are related to cognitive processes; in fact, it is globally recognized as the main structure of memory. However, it has been shown how this region performs two other activities apart from memorization processes: the inhibition of behavior and spatial orientation.

Hippocampus Illustration

The hippocampus, from the Latin hippocampus, was discovered in the 16th century by the anatomist Giulio Cesare Aranzio. It owes its name to the appearance of its structure, which resembles the shape of the seahorse, hippocampus.

Comparison between dissected hippocampus and seahorse

Initially, there was some controversy about the anatomy of this region of the brain and it was given different names such as "silkworm" or "ram's horn." Likewise, the existence of two different regions of the hippocampus was proposed: "greater hippocampus" and "minor hippocampus".

At present, this subdivision of the hippocampus has been disregarded and it is classified as a single structure. On the other hand, in its discovery, the hippocampus was related to the sense of smell, and it was defended that this brain structure was in charge of processing and recording olfactory stimuli.

It was not until 1900 when, by Vladimir Bekhterev, the actual functioning of the structure was demonstrated and the memory functions performed by the hippocampus began to be investigated.

Anatomy and location of the hippocampus

The hippocampus is a brain region that is located at the end of the cortex. Specifically, it is an area where the cortex narrows into a single layer of densely packed neurons.

Thus, the hippocampus is a small region found at the lower border of the cerebral cortex, comprising ventral and dorsal portions.

Illustration of a hippocampus

Due to its location, it is part of the limbic system, that is, of the group of regions found in the region that borders the cerebral cortex, and exchanges information with different brain regions.

The limbic system. Source: Anatomy & Physiology, Connexions, OpenStax College via Wikimedia Commons

On the one hand, the major source of hippocampal afferents is the entorhinal cortex and it is strongly connected with a large number of regions of the cerebral cortex. Specifically, the hippocampus appears to be closely related to the prefrontal cortex and the lateral septal area.

The connection of the hippocampus with these areas of the cortex explains much of the cognitive processes and memory functions performed by the structure.

On the other hand, the hippocampus is also connected to the lower regions of the brain. This region has been shown to receive modulatory inputs from the serotonergic, dopaminergic, and norepinephrine systems, and is strongly connected to the thalamus.

Physiology

Hippocampus

The hippocampus works through two modes of activity, each with a different pattern of functioning and with the participation of a specific group of neurons. These two modes of activity are theta waves and major patterns of irregular activity (LIA).

Theta waves appear during states of alertness and activity, as well as during REM sleep. During this time, that is, when we are awake or in REM sleep phase, the hippocampus works by means of long and irregular waves produced by pyramidal neurons and granule cells.

For its part, irregular activity appears during sleep (except in REM phase) and in moments of immobility (when we eat and rest).

Likewise, it seems that angular slow waves are the ones that are most closely related to memory processes.

In this way, the moments of rest would be key so that the hippocampus can store and retain the information in its brain structures.

Functions of the hippocampus

Hippocampus (red)

The initial hypothesis that the hippocampus performed functions related to the sense of smell has been superseded. In fact, the falsity of this possible hippocampal function was demonstrated and it has been shown that, despite the fact that this region receives direct input from the olfactory bulb, it does not participate in sensory functioning.

Over the years, the functioning of the hippocampus was related to the performance of cognitive functions. Currently, the functionality of this region focuses on three main aspects: inhibition, memory and space.

The first of these arose in the 1960s through O'keefe and Nadel's behavior inhibition theory. In this sense, the hyperactivity and inhibition difficulty observed in animals with lesions in the hippocampus developed this theoretical line and related the functioning of the hippocampus with behavioral inhibition.

Regarding memory, it became related to the famous article by Scoville and Brenda Milner, which described how the surgical destruction of the hippocampus in a patient with epilepsy caused anterograde amnesia and a very serious retrograde amnesia.

The third and final function of the hippocampus was initiated by Tolman's "cognitive mapping" theories and O'Keefe's discovery that neurons in the hippocampus of rats appeared to show activity related to location and spatial situation.

Hippocampus and inhibition

The discovery of the role of the hippocampus in behavioral inhibition is quite recent. In fact, this feature is still under investigation.

Recent studies have focused on examining a specific region of the hippocampus called the ventral hippocampus. In the investigation of this small region, it has been postulated that the hippocampus could play an important role in both behavioral inhibition and the development of anxiety.

The most important study on these functions was conducted a few years ago by Joshua A. Gordon. The author recorded the electrical activity of the ventral hippocampus and medial prefrontal cortex in mice by exploring different environments, some of which elicited anxiety responses in the animals.

The study focused on seeking the synchronization of brain activity between brain regions, since this factor constitutes a sign of information transfer. Because the hippocampus and the prefrontal cortex are connected, the synchronization was evident in all environments in which the mice were exposed.

However, in situations that produced anxiety in animals, it was observed that the synchronization between both brain parts increased.

Likewise, it was also demonstrated how the prefrontal cortex experienced an increase in theta rhythm activity when the mice were in environments that produced fear or anxiety responses.

This increase in theta activity was related to a notable decrease in the exploration behavior of the mice, for which it was concluded that the hippocampus is the region in charge of transmitting the information necessary to inhibit certain behaviors.

Hippocampus and memory

Unlike the role that the hippocampus plays in inhibition, today there is a high scientific consensus in affirming that this region constitutes a vital structure for the functioning and development of memory.

Mainly, it is argued that the hippocampus is the brain structure that allows the formation of new memories of the events experienced, both episodic and autobiographical. In this way, it is concluded that the hippocampus is the area of ​​the brain that allows learning and retention of information.

These hypotheses have been widely demonstrated both by multiple neuroscientific investigations and, above all, by the symptoms produced by lesions in the hippocampus.

Severe injuries to this region have been shown to cause profound difficulties in the formation of new memories and often affect memories formed before injury as well.

However, the main role of the hippocampus in memory lies more in learning than in the retrieval of previously stored information. In fact, when people form a memory, it is first stored in the hippocampus but with the passage of time the information accesses other regions of the temporal cortex.

Likewise, the hippocampus does not seem to be an important structure in the learning of motor or cognitive skills (how to play an instrument or solve logic puzzles).

This fact reveals the presence of different types of memory, which are governed by different brain regions, so that the hippocampus does not cover all memory processes in full, but a good part of them does.

Hippocampus and spatial orientation

Research in rat brains has shown that the hippocampus contains a series of neurons that have "place fields." This means that a group of neurons in the hippocampus trigger action potentials (transmit information) when the animal passes a specific place in its environment.

Likewise, Edmund Rolls described how certain neurons in the hippocampus are activated when the animal focuses its gaze on certain aspects of its environment.

Thus, studies with rodents have shown that the hippocampus could be a vital region in the development of orientation capacity and spatial memory.

In humans the data are much more limited due to the difficulties posed by this type of research. However, "site neurons" were also found in subjects with epilepsy who performed an invasive procedure to locate the source of their seizures.

In the study, electrodes were placed on the hippocampus of individuals and they were subsequently asked to use a computer to navigate a virtual environment that represented a city.

Related diseases

Lesions in the hippocampus produce a series of symptoms, most of them related to memory loss and especially a decrease in learning capacity.

However, memory problems caused by severe injury are not the only diseases related to the hippocampus. In fact, four major diseases seem to have some kind of link to the functioning of this brain region. These are:

Brain degeneration

Brain of Alzheimer's patient.

Both normal and pathological aging of the brain appear to be closely related to the hippocampus.

Memory problems related to age or the decline in cognitive abilities experienced during old age are related to a decrease in the neuronal population of the hippocampus.

This relationship becomes much more noticeable in neurodegenerative diseases such as Alzheimer's, in which a massive death of neurons in this brain region is observed.

Stress

The hippocampus contains high levels of mineralocorticoid receptors, making this region highly vulnerable to stress.

Stress can affect the hippocampus by reducing excitability, inhibiting genesis and causing atrophy of some of its neurons.

These factors explain the cognitive problems or memory failures that we can experience when we are stressed, and they are especially noticeable among people with post-traumatic stress disorder.

Epilepsy

The hippocampus is frequently the focus of epileptic seizures. Hippocampal sclerosis is the most commonly visible type of tissue damage in temporal lobe epilepsy.

However, it is not clear whether epilepsy occurs due to abnormalities in the functioning of the hippocampus or whether epileptic seizures produce abnormalities in the hippocampus.

Schizophrenia

Schizophrenia is a neurodevelopmental disease that involves the presence of numerous abnormalities in the brain structure.

The region most associated with the disease is the cerebral cortex, however, the hippocampus could also be important, since it has been shown that many subjects with schizophrenia present a notable decrease in the size of this region.

References

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