The hippocampus and its role in the brain

Anatomy

The hippocampus is a structure of the brain that plays a fundamental role in learning and memory. It is damaged in Alzheimer’s disease.

Knowing about the hippocampus has helped researchers understand how memory works.

Location

The hippocampus is a structure of the brain that is part of the temporal lobe of the cerebral cortex.

The name comes from the Greek words hippo, meaning horse, and kampo, meaning monster, because its shape resembles that of a sea horse. It has a C shape.

The hippocampus is a brain structure located in the temporal lobe. It plays a major role in learning and memory.

The hippocampus is part of the limbic system. It is found under the cortex.

The limbic system is considered a « primitive brain », located deep in the brain. It is involved in hunger, motivation, libido, mood, pain, pleasure, appetite and memory, etc.

The hippocampus is the part of the brain that is one of the most widely studied. Its atrophy has clinical consequences.

It is the earliest and most severely affected structure in several neurological disorders such as Alzheimer’s disease or epilepsy.

In adults, the volume of the hippocampus on each side of the brain is approximately 3-3.5 cm 3 while the volume of the cerebral cortex is approximately 320-420 cm 3.

Thus, the hippocampus is 100 times smaller than the cerebral cortex.

Papez (1930) proposed that the emotional reaction is organized in the hippocampus and is expressed in the cingulate gyrus. He is also involved in recalling past experience and how to imagine the future.

But its best-known role is that in learning and short-term memory.

Anatomy

The hippocampus contains two parts: the Cornu ammonis or horn of Ammon (with its CA1, CA2, CA3 and CA4 regions) and the dentate gyrus. These two parts are separated by the sulcus. Finally there is the entorhinal region (EC). 

The whole is called hippocampal formation.

The hippocampus is divided into a head, a body and a tail; the head being an enlarged part while the tail is a thin part.

Just in front of CA1 is the subiculum that connects the hippocampus to the entorhinal cortex.

The hippocampus is supplied with blood by the posterior cerebral artery, which has three branches: anterior, middle and posterior. The veins of the hippocampus go through the basal vein.

Hippocampus and memory

The hippocampus can process and recover two types of memory, episodic memory and spatial memory.

The episodic memory is related to facts and events. 

Spatial memory involves paths or routes. For example, when a taxi driver learns a route through a city, he uses spatial memory. 

The hippocampus is also where short-term memories are turned into long-term memories. These are then stored elsewhere in the brain.

Research has shown that neurons continue to develop throughout adulthood. The hippocampus is one of the rare places in the brain to generate new nerve cells: it is neurogenesis.

The HM case

The role of the hippocampus in memory was particularly revealed in the case of Henry Gustav Molaison (called HM). Partial anterograde and retrograde amnesia developed in this patient following the removal of his hippocampus due to refractory epilepsy. HM was unable to form new episodic memories after this surgery. In other words, he was no longer learning new things and not remembering what he had learned before the operation. In medical science, HM is perhaps the most studied patient. 

Subsequent studies have shown that damage to the hippocampus causes anterograde amnesia and often retrograde amnesia as well. Implicit memory is spared due to damage to the hippocampus.

The hippocampus is now known not only to be important in learning and memory, but also in:

  • Orientation in space
  • Emotional behavior.

The regulation of the functions of the hypothalamus and consequently the release of cortisol, the stress hormone.

Hippocampus and memory loss

Transient global amnesia is a specific form of memory loss that develops suddenly, apparently on its own, and then goes away fairly quickly.

Most people with transient global amnesia eventually regain their memories, but it’s unclear why the problem occurs and why it resolves. Damage to the hippocampus may be involved.

Damage to the hippocampus can make it difficult to remember how to get from one place to another. The person may be able to draw a map of the neighborhood they lived in as a child, but it may be difficult for them to go to a store in a new neighborhood.

It has also been linked to diseases such as schizophrenia and post-traumatic stress disorder .

Lesions of the hippocampus associated with diseases of the brain

The hippocampus is a sensitive part of the brain. A range of illnesses can negatively affect it, including long-term exposure to high levels of stress.

Several diseases and factors are known to interfere with the ability of the hippocampus to function normally.

Alzheimer’s disease

The atrophy of the hippocampus region of the brain is one of the features most consistent with Alzheimer’s disease. It is the most severely affected region of the brain. 

One hypothesis has proposed that early lesions of the hippocampus cause « dissociation » between the hippocampus and the cerebral cortex, leading to failure to record information from the hippocampus. Hippocampal atrophy is used as both a diagnostic and prognostic marker in clinical trials for Alzheimer’s disease. It has been observed that patients with mild cognitive impairment have 10-15% loss of hippocampal volume while in those with early-onset Alzheimer’s disease this loss is approximately 15-30%. In those with moderate Alzheimer’s disease, it can reach 50%.

Depression

It is increasingly recognized that prolonged depression can lead to loss of hippocampal volume. In addition, the duration of depression was correlated with the severity of hippocampal atrophy. Evidence suggests that the atrophy so produced may be permanent and persist for a long time even if there is remission. In people with depression, the hippocampus can shrink by up to 20%, according to some researchers. It has been speculated that this could be the result of prolonged stress generated by depression. Suppression of neurogenesis (production of new neurons) in the hippocampus could be the cause.

Schizophrenia

Reduction in hippocampal volume is one of the findings observed by MRI in schizophrenic patients. It is less marked than that observed in Alzheimer’s disease. 

Epilepsy

Up to 50% to 75% of patients with epilepsy may have atrophy of the hippocampus during postmortem analysis. However, it is not clear whether epilepsy occurs as a result of hippocampal sclerosis or repeated seizures damaging the hippocampus. This means that it is not yet clear whether damage to the hippocampus is a cause or a consequence of recurrent seizures.

The hippocampus is believed to have an inhibitory effect on the seizure threshold (i.e., it maintains the threshold high). Once it is damaged, the seizures become more uncontrollable.

Cushing’s disease

Cushing’s disease has a number of symptoms related to high levels of cortisol, a hormone produced when people are under stress. 

A loss of hippocampal volume has been observed in Cushing’s disease. There is evidence to suggest that if Cushing’s disease is treated, the atrophy of the hippocampus may be reversible.

Ongoing research

In 2016, scientists published a review of studies on the effects of exercise on cognitive decline and aging of the brain.

The results suggest that exercise may enhance the ability of this structure to generate new nerve cells (neurogenesis). This would preserve and potentially improve memory. This hypothesis remains to be confirmed.

Conclusions

The hippocampus, located in the temporal lobe, plays a central role in memory. It is a vulnerable and plastic structure, which can change. Its atrophy is one of the markers of cognitive decline and the diagnosis of Alzheimer’s disease.