Theories Three main theories of hippocampal function have been in dominance:
response inhibition,
episodic memory, and
spatial cognition. The response inhibition theory (caricatured by
John O'Keefe and
Lynn Nadel as "slam on the brakes!") was very popular up to the 1960s. It was based largely on two observations: first, that animals with hippocampal damage tend to be
hyperactive; second, that animals with hippocampal damage often have difficulty learning to inhibit previously learnt responses, especially if the response requires remaining quiet as in a
passive avoidance test. British psychologist
Jeffrey Gray developed this line of thought into a complete theory of the role of the hippocampus in
anxiety, called the
behavioral inhibition system. The second major line of thought relates the hippocampus to memory. Although it had historical precursors, this idea derived its main impetus from a famous report by American neurosurgeon
William Beecher Scoville and British-Canadian neuropsychologist
Brenda Milner. It described the results of surgical destruction of the hippocampi when trying to relieve
epileptic seizures in an American man
Henry Molaison, known until his death in 2008 as "Patient H.M." The unexpected outcome of the surgery was severe
anterograde, and partial
retrograde amnesia; Molaison was unable to form new
episodic memories after his surgery and could not remember any events that occurred just before his surgery, but he did retain memories of events that occurred many years earlier extending back into his childhood. This case attracted such widespread professional interest that Molaison became the most intensively studied subject in medical history. A book was later produced in 1978,
The Hippocampus as a Cognitive Map written by O'Keefe and Nadel. It has been generally agreed that the hippocampus plays a key role in spatial coding but the details are widely debated. Research has focused on trying to bridge the disconnect between the two main views of hippocampal function as being split between memory and spatial cognition. In some studies, these areas have been expanded to the point of near convergence. In an attempt to reconcile the two disparate views, it is suggested that a broader view of the hippocampal function is taken and seen to have a role that encompasses both the organization of experience (
mental mapping, as per Tolman's original concept in 1948) and the directional behavior seen as being involved in all areas of cognition, so that the function of the hippocampus can be viewed as a broader system that incorporates both the memory and the spatial perspectives in its role that involves the use of a wide scope of cognitive maps. This relates to the
purposive behaviorism born of Tolman's original goal of identifying the complex cognitive mechanisms and purposes that guided behavior. It has also been proposed that the spiking activity of hippocampal neurons is associated spatially, and it was suggested that the mechanisms of memory and planning both evolved from mechanisms of navigation and that their neuronal algorithms were basically the same. Many studies have made use of
neuroimaging techniques such as
functional magnetic resonance imaging (fMRI), and a functional role in
approach-avoidance conflict has been noted. The anterior hippocampus is seen to be involved in decision-making under approach-avoidance conflict processing. It is suggested that the memory, spatial cognition, and conflict processing functions may be seen as working together and not mutually exclusive.
Role in memory The hallmark function of the hippocampus is the formation of
explicit memory, also known as declarative memory. The hippocampus also encodes emotional context from the
amygdala. This is partly why returning to a location where an emotional event occurred may evoke that emotion. There is a deep emotional connection between episodic memories and places. Due to
bilateral symmetry the brain has a hippocampus in each
cerebral hemisphere. If damage to the hippocampus occurs in only one hemisphere, leaving the structure intact in the other hemisphere, the brain can retain near-normal memory functioning. Severe damage to the hippocampi in both hemispheres results in profound difficulties in forming new memories (
anterograde amnesia) and often also affects memories formed before the damage occurred (
retrograde amnesia). Although the retrograde effect normally extends many years back before the brain damage, in some cases older memories remain. This retention of older memories leads to the idea that
consolidation over time involves the transfer of memories out of the hippocampus to other parts of the brain. Experiments using intrahippocampal transplantation of hippocampal cells in primates with neurotoxic lesions of the hippocampus have shown that the hippocampus is required for the formation and recall, but not the storage, of memories. It has been shown that a decrease in the volume of various parts of the hippocampus leads to specific memory impairments. In particular, efficiency of verbal memory retention is related to the anterior parts of the right and left hippocampus. The right head of the hippocampus is more involved in executive functions and regulation during verbal memory recall. The tail of the left hippocampus tends to be closely related to verbal memory capacity. Damage to the hippocampus does not affect some types of memory, such as the ability to learn new skills (playing a musical instrument or solving certain types of puzzles, for example). This fact suggests that such abilities depend on different types of memory such as
procedural memory in
implicit memory function, implicating different brain regions. Furthermore, amnesic patients frequently show implicit memory for experiences even in the absence of conscious knowledge. For example, patients asked to guess which of two faces they have seen most recently may give the correct answer most of the time in spite of stating that they have never seen either of the faces before. Some researchers distinguish between conscious
recollection, which depends on the hippocampus, and
familiarity, which depends on portions of the medial temporal lobe. A study claims to have confirmed that the hippocampus is not associated with implicit memory. But other sources say the question is still up for debate (as of 2024). When rats are exposed to an intense learning event, they may retain a life-long memory of the event even after a single training session. The memory of such an event appears to be first stored in the hippocampus, but this storage is transient. Much of the long-term storage of the memory seems to take place in the
anterior cingulate cortex. When such an intense learning event was experimentally applied, more than 5,000
differently methylated DNA regions appeared in the hippocampus
neuronal
genome of the rats at one hour and at 24 hours after training. These alterations in
methylation pattern occurred at many
genes that were
down-regulated, often due to the formation of new
5-methylcytosine sites in
CpG rich regions of the genome. Furthermore, many other genes were
upregulated, likely often due to the
removal of methyl groups from previously existing
5-methylcytosines (5mCs) in DNA. Demethylation of 5mC can be carried out by several proteins acting in concert, including
TET enzymes as well as enzymes of the DNA
base excision repair pathway.
Between systems model The
between-systems memory interference model describes the inhibition of non-hippocampal systems of memory during concurrent hippocampal activity. Specifically it was found that when the hippocampus was inactive, non-hippocampal systems located elsewhere in the brain were found to
consolidate memory in its place. However, when the hippocampus was reactivated,
memory traces consolidated by non-hippocampal systems were not recalled, suggesting that the hippocampus interferes with
long-term memory consolidation in other memory-related systems. One of the major implications that this model illustrates is the dominant effects of the hippocampus on non-hippocampal networks when information is incongruent. With this information in mind, future directions could lead towards the study of these non-hippocampal memory systems through hippocampal inactivation, further expanding the labile constructs of memory. Additionally, many theories of memory are holistically based around the hippocampus. This model could add beneficial information to hippocampal research and memory theories such as the
multiple trace theory. Lastly, the between-system memory interference model allows researchers to evaluate their results on a
multiple-systems model, suggesting that some effects may not be simply mediated by one portion of the brain.
Role in spatial memory and navigation s of eight
place cells recorded from the
CA1 layer of a rat. The rat ran back and forth along an elevated track, stopping at each end to eat a small food reward. Dots indicate positions where
action potentials were recorded, with color indicating which neuron emitted that action potential. There are several types of
navigational cells in the brain that are either in the hippocampus itself or are strongly connected to it. They include the
place cells,
speed cells present in the
medial entorhinal cortex,
head direction cells,
grid cells, and
boundary cells. Together these cells form a network that serves as
spatial memory. The first of these types of cell discovered in the 1970s were the place cells, which led to the idea of the hippocampus acting to give a neural representation of the environment in a
cognitive map. Studies with animals have shown that an intact hippocampus is required for initial learning and long-term retention of some spatial memory tasks, in particular ones that require finding the way to a hidden goal. Studies on freely moving rats and mice have shown many hippocampal
neurons to act as
place cells that cluster in
place fields, and these fire bursts of
action potentials when the animal passes through a particular location. Hippocampal place cells interact extensively with head direction cells, whose activity acts as an inertial compass, and conjecturally with grid cells in the neighboring entorhinal cortex. Speed cells are thought to provide input to the hippocampal grid cells. This place-related neural activity in the hippocampus has also been reported in monkeys that were moved around a room whilst in a restraint chair. However, the place cells may have fired in relation to where the monkey was looking rather than to its actual location in the room. Over many years, many studies have been carried out on place-responses in rodents, which have given a large amount of information. The firing of place cells is timed in relation to local
theta waves, a
spatiotemporal process termed
phase precession. Cells with location-specific firing patterns have been reported during a study of people with
drug-resistant epilepsy. They were undergoing an invasive procedure to localize the source of their
seizures, with a view to surgical resection. They had diagnostic electrodes implanted in their hippocampi and then used a computer to move around in a
virtual reality town. Similar
brain imaging studies in
navigation have shown the hippocampus to be active. A study was carried out on taxi drivers. London's
black cab drivers need to learn the locations of a large number of places and the fastest routes between them in order to pass a strict test known as
The Knowledge in order to gain a license to operate. A study showed that the posterior part of the hippocampus is larger in these drivers than in the general public, and that a positive correlation exists between the length of time served as a driver and the increase in the volume of this part. It was also found the total volume of the hippocampus was unchanged, as the increase seen in the posterior part was made at the expense of the anterior part, which showed a relative decrease in size. There have been no reported adverse effects from this disparity in hippocampal proportions. Another study showed opposite findings in blind individuals. The anterior part of the right hippocampus was larger and the posterior part was smaller, compared with sighted individuals.
Role in approach-avoidance conflict processing Approach-avoidance conflict happens when a situation is presented that can either be
rewarding or punishing, and the ensuing decision-making has been associated with
anxiety.
fMRI findings from studies in approach-avoidance decision-making found evidence for a functional role that is not explained by either long-term memory or spatial cognition. Overall findings showed that the anterior hippocampus is sensitive to conflict, and that it may be part of a larger cortical and subcortical network seen to be important in decision-making in uncertain conditions. Associations among facial and vocal identity were similarly mapped to the hippocampus of rhesus monkeys. Single neurons in the CA1 and CA3 responded strongly to social stimulus recognition by MRI. The CA2 was not distinguished, and may likely comprise a proportion of the claimed CA1 cells in the study. The dorsal CA2 and ventral CA1 subregions of the hippocampus have been implicated in social memory processing. Genetic inactivation of CA2 pyramidal neurons leads to pronounced loss of social memory, while maintaining intact sociability in mice. Similarly, ventral CA1 pyramidal neurons have also been demonstrated as critical for social memory under optogenetic control in mice.
Role in olfaction In the early 20th century, the widely held view was that
olfaction was a major hippocampal function. This view was argued against, pointing out that the hippocampus was present in some animals such as
dolphins and
whales, that did not have a sense of smell; and further that lesions in the temporal lobe in dogs had been shown to have no effect on their sense of smell. == Physiology ==