The Hippocampus

The “hippocamp” is a mythical creature from Greek mythology: the front part of a horse, but with the torso and tail of a fish. The hippocampi were the mount and draft of various sea gods. The real-life seahorses are named after them. Or the hippocampi are named after them, no one knows.

If you cut the cerebrum horizontally – roughly at eye level – and lift off the “lid” (so that you can see into the inner cavities of the brain, the ventricles), then visible to the naked eye at the bottom of the right and left lateral ventricles of the temporal lobes is a structure about the length of a little finger, elongated, worm-like, and not at all horse-headed. This is the neuroanatomy of the hippocampus. Why the Venetian anatomist Julius Caesar Arantius, who coined this term in the 16th century, was reminded of sea horses is completely unclear. Nevertheless the mythological, fish-like name has stuck to this day. After all, even if the horse's head is missing, the hippocampus does have a very long, curved “tail” at the back, known as the fornix. This bundles not all, but many of the fiber systems through which the hippocampus connects to other regions of the brain.
 

The hippocampus is a cortical structure and is a large integration area with connections to all areas of the cortex and the limbic system. It is classified as part of the archicortex. Like the rest of the cortex, its various subunits – the subiculum, cornus ammonis, and fascia dentata – consist entirely of plate-like layers of neurons. The anatomical terms are once again colourful; the dentate gyrus is the “toothed band,” the cornus ammonis is the “ram's horn,” and the subiculum is a “seat cushion”. It's all very figurative – after all, the dentate gyrus looks like a tooth, the ram's horn is curved, and the entire hippocampus sits on top of the subiculum.

The cortex of the hippocampus does not have the typical six layers of the isocortex, which is why it is also referred to as the allocortex (i.e., “other cortex”). Another typical feature of the hippocampus is the “curling” of these plate-like cortices. When a cross-sectioned is viewed under the microscope, it resembles a pancake lying on its side, with the fascia dentata on the inside and the cornu ammonis wrapped around it.
 
The main inputs to the hippocampus come from the entorhinal cortex, which is located immediately adjacent to it, right next to the subiculum. They run in the tractus perforans. The entorhinal cortex is itself connected to many association areas of the neocortex. Inside the hippocampus, between its various divisions (see above), there is a fairly stereotypical “circuit”: the axons of the perforant pathway end at the neurons of the dentate gyrus, whose axons extend to the dendrites of the nerve cells in the cornu ammonis, which in turn send their axons partly to the fornix and partly to the subiculum. This in turn sends its nerve fibers both to the fornix and back to the entorhinal cortex. The hippocampus therefore has two “main outputs”: (1) via the fornix to the mammillary bodies of the hypothalamus and to the hippocampal formation in the opposite temporal lobe, and (2) via the subiculum back to the entorhinal cortex. The hippocampus is therefore part of the Papez circuit. Despite this canonical, “rigid” circuit, the hippocampus is (also anatomically) an extremely plastic and dynamic structure (see below).

The function of a structure can best be assessed when it fails. And so, we now know that the absence of just one hippocampus is tolerable, however, if both are missing the effect is dramatic. In fact, there have been patients who had to have both hippocampi removed in order to treat otherwise incurable epilepsy. The best-known of these patients is Henry Gustav Molaison (1926–2008), who went down in medical literature as H. M. He became famous for a very typical memory disorder – an anterograde amnesia, which can occur after an accident involving traumatic brain injury. It affects declarative memory, i.e., the knowledge one has about oneself and the world – from the moment of the triggering event onwards. Motor memory, general finger and movement skills, is not affected.

An anterograde amnesiac can still recall, albeit to a limited extent, the world and autobiographical knowledge they had before the failure of both hippocampi. However, they cannot form new memories, i.e. acquire new knowledge. Time stands still for them; their bodies may age, but their minds remain young. They cannot remember anything for more than a few seconds or minutes. They cannot find anything that they have not stored in the place where they have always kept it. Moving house is perilous as they cannot find their way around a new environment.

These clinical findings are consistent with the fact that the hippocampi of animals that “need to remember well” – squirrels that hide nuts, but also some birds that store food – are extremely large compared to other species that live “from hand to mouth.” Nerve cells have also been found in the hippocampi of rodents that are active only when the animal is in a specific location – these are known as place cells. 

A (unfortunately) well-known disease, Alzheimer's dementia, also affects the hippocampus and its surrounding area in its early stages. Neurons of the entorhinal cortex, from which the tractus perforans emerges (see above), are destroyed at an early stage in Alzheimer's disease, with the result that the hippocampus is deprived of its neocortical “inputs” and thus loses the cognitive material that would normally be used to form memories. Memory disorders are the result.
 

Finally, the neural mechanism believed to be the physiological substrate of learning has been discovered in the hippocampus – more precisely, in the interaction of its nerve cells: long-term potentiation (LTP). In short, nerve cells that fire together, wire together. The underlying LTP is based on a change in the synapses. In the case of synchronization, the transmission from one neuron to another becomes more effective. To put it bluntly, the “synaptic resistance” decreases.

However, the synapses in the hippocampus are also constantly changing their shape and number. Almost like buds, they can sprout or shrink away from each other, just as if they were drying up, to stick with the image of buds. This so-called synaptic plasticity plays a decisive role in the activity-dependent modulation of the interconnection of nerve cells.

It has recently been discovered that the hippocampus – its dentate gyrus, to be precise – is one of the few places in the brain where neurons are born throughout life. This is called neurogenesis. We do not yet fully understand what purpose it serves, the newly born nerve cells are integrated into the existing, highly complex intrinsic circuits of the hippocampus. There is evidence that disturbances in this neurogenesis may be linked to depression.

First published on August 23, 2011
Last updated on April 14, 2025