The Hippocampus

Role of the Hippocampus in Remembering Information

Buried deep within the medial temporal lobe of the human brain lies the hippocampal system—a group of many millions of neurons organized into a network quite different from that found anywhere else in the nervous system. It is a structure consisting of the hippocampus, our subject of focus, and many other areas including the dentate gyrus, subiculum, presubiculum, parasubiculum, and entorhinal cortex.

The hippocampus, long known to be important for memory, plays a significant role in the encoding and retrieval of long-term memory for facts and events. It is critically involved in “declarative” or “explicit” form of memory but is not involved in other forms of long term memory, in nonmnemonic aspects of cognition, or in immediate working memory. Furthermore, its involvement in declarative memory is not permanent but is time-limited in nature.

Patient H.M.—The Man Who Never Got Older

It would be almost impossible to begin a discussion of the role of the hippocampus in human memory without considering the classic case of a patient known in scientific literatures by the initials “H.M.”. Parts of the brain are sometimes lesioned to help people with epilepsy overcome epileptic seizures.

In H.M.’s case, the medial portions of the temporal lobe, which housed the hippocampus was removed (Milner, 1966). Right after the operation, H.M.’s mental functioning appeared normal. As time went, however, it became clear that he had problems processing new information. For example, two years after the operation, H.M. believed he was twenty-seven—his age at the time of the operation.

When his family moved to a new address, H.M. could not find his new home or remember the route to locate the address. He responded with appropriate grief to the death of his uncle, yet he then began to ask about his uncle and why he did not visit. Each time he was reminded of his uncle’s passing, he grieved as if he were hearing it for the first time.

H.M.’s operation apparently prevented him from transferring information from short-term to long-term memory, a process in which the hippocampus is critically involved in neurologically intact individuals.

Subsequent Findings

Subsequent testing of H.M. was able to reveal not only the breadth and severity of H.M.’s memory impairment but, critically, it also showed a vast array of cognitive and mnemonic function that was unaffected by the lesion of the temporal lobe. The pattern of data allowed Milner (Milner et al., 1968; Milner, 1972) to make several conclusions that expanded on those noted above and helped lay the foundation for subsequent investigation into the amnesic syndrome.

1. First, Milner noted that damage to the medial portions of the temporal lobe results in profound inability to acquire long-term memory for new facts or events (anterograde amnesia) although memories from early life appear to be intact. Conversely, there was some clear loss of memory of information acquired for some time prior to the operation (retrograde amnesia). Together, these observations indicated that the medial temporal lobe might not be a permanent repository for memory but that it plays a time-limited, albeit critical, role in memory.
2. Second, she noted that there was no loss in general intellect or perceptual ability, indicating clear dissociation between memory and other aspects of cognition.
3. Third, she noted that short-term memory remained intact, indicating clear dissociation between immediate, or working memory Opens in new window and permanent, long-term memory.
4. Finally, she noted that damage to the medial portions of the temporal lobe did not abolish all forms of long-term learning and memory, indicating that the medial temporal lobes were not required for at least some forms of long-term memory.

In a more recent extension of these conclusions, Squire and Zola-Morgan (1991) identified what they referred to as a medial temporal lobe memory system (MTL), consisting of the hippocampal region (identified as the CA fields of the hippocampus proper, the dentate gyrus, and the subiculum) and the adjacent entorhinal, perirhinal, and parahippocampal cortices (which together form the parahippocampal gyrus).

Together, this system is posited to be critically involved in the acquisition of new fact (“semantic”) and event (“episodic”) memory. Notably, this system is not the permanent storage site for this “declarative” or “explicit” memory, nor is it the locus of other cognitive functions or other forms of memory. For example, it is not involved in immediate or working memory, and it is not involved in a wide range of “nondeclarative” or “implicit” long-term memory tasks (e.g., delay conditioning, perceptual repetition priming, habit learning). These ideas amplify and develop Milner’s suppositions in several ways.

To bring this discussion to a close, the hippocampus is engaged in remembering information that can be described in a propositional or declarative manner.

The hippocampus is also involved in a number of disparate neurological disorders, including epilepsy, Alzheimer’s disease, and cerebrovascular disease. Thus, the abnormal electrical activity that is at the root of seizures in epileptic patients is often easily detected in the hippocampus.

Moreover, a hallmark feature of the neuropathology of temporal lobe epilepsy is loss of neurons in several hippocampal fields. For example, the characteristic pathological changes of Alzheimer’s disease manifest initially in the entorhinal cortex—one of the components of the hippocampal formation—and the disease spreads from there to involve the hippocampus proper and ultimately the entire cerebral cortex. Such findings have led to the development of model systems in which patho-physiological events such as these may be studied and, hopefully, alleviated by treatment.