Hippocampus
The hippocampus is a vital brain structure primarily associated with memory and spatial navigation. Located deep within the temporal lobe, humans and all mammals possess two hippocampi, one in each hemisphere. Historically, the understanding of its function has evolved; earlier theories linked it primarily to olfactory and emotional processes, but modern research emphasizes its critical role in memory acquisition, particularly episodic memory, and spatial representation. Groundbreaking studies, including the case of patient H. M., have elucidated the hippocampus's involvement in memory, revealing the profound impacts of its damage on memory formation and recall.
Recent discoveries, such as place cells and grid cells, have further highlighted the hippocampus's role in creating cognitive maps of space, while time cells have introduced a temporal aspect to spatial navigation. Research continues to explore the hippocampus's connections to other regions of the brain and its involvement in broader functions beyond memory, including stress response and emotion. The structure's vulnerability to conditions like epilepsy, Alzheimer's disease, and chronic stress underscores its significance in both health and disease, inviting ongoing investigation into its complex functions and connections.
Hippocampus
The hippocampus is a brain structure that plays a critical role in memory and spatial navigation, although the specifics of that role remain a central topic of debate within a rapidly expanding field of research. The name derives from an early comparison of the structure to a seahorse (from the Greek hippo, meaning horse, and kampos, meaning sea). It is an elaboration of the edge of the cortex and is located deep in the innermost fold of the temporal lobe. It is a bilateral structure, meaning the brain has two hippocampi, one on either side. All mammals have a hippocampus, and connectivity and functionality are generally similar across species.
Brief History
Early theories about hippocampal function centered primarily on olfaction, emotion, and inhibition, although these have largely been discounted in favor of theories relating the hippocampus to memory mediation and spatial representation. In the 1950s, a patient known as H. M. underwent surgical destruction of the hippocampus and surrounding areas in an effort to treat epileptic seizures, and the dramatic results have fueled hippocampal research ever since. While the surgery successfully reduced the number of seizures, H. M.’s memory was drastically impaired; while he was able to recall events from his childhood, he suffered from both the inability to recall events in the years leading up to the surgery, and the inability to form new memories following the procedure. These findings permitted certain areas of the human brain to be linked to specific amnesia for the first time, and H. M. became the most intensively studied subject in medical history. Because H. M. demonstrated improvement on tasks requiring motor skills or short-term recollection, his case was foundational for suggesting differentiations between various kinds of memory and how each type might be mediated in the brain.
Based on extensive studies, the hippocampus was connected to memory acquisition and retrieval, especially episodic memory, which involves recollection of previously experienced events. An important study in 1997 observed impairments in episodic memory in amnesiacs with damage more precisely localized to the hippocampus alone, lending substantial support to this perspective.
Another landmark development in hippocampal research was the 1971 discovery by John O’Keefe of place cells in the rodent hippocampus. Recording neurons in the hippocampi of rats moving around freely within a bounded area, O’Keefe and his student, Jonathan Dostrovsky, noticed that certain cells fire in accordance with a rat’s particular spatial location in the environment (the place field). In 1978, O’Keefe and Lynn Nadel published the remarkably influential book, The Hippocampus as a Cognitive Map, in which they elaborated a theory that the collective activity of such place cells could provide the rat with a kind of neural representation of space referred to as a cognitive map. Various behavioral studies that demonstrate impaired spatial learning in rodents with hippocampal damage further support this view.
Overview
The hippocampus comprises various types of neurons, and much research following O’Keefe’s discovery has been dedicated to investigating those neurons to gain a better understanding of hippocampal function more broadly. A key development in this regard was the discovery by May-Britt Moser and Edvard Moser of grid cells in 2005, as they were searching for the basis of place cell firing. Grid cells generate a remarkably regular, triangular, grid-like representation of space. These cells were found in the rodent entorhinal cortex, a major input into the hippocampus. A number of other spatially oriented cells have also been found in areas with strong connections to the hippocampus, providing convincing evidence that the hippocampus is involved in generating an internal representation of space and, given the multiple dimensions encoded, acting as a sort of "inner GPS." While this work was primarily developed with rodents, place cells were discovered in the human hippocampus in 2012 and grid cells in the human entorhinal cortex in 2013.
The discovery of time cells, which fire at specific time intervals while the animal stays in place, has also pointed up a temporal correlate to place cells, offering insight into how episodic memory is encoded. However, time cells and place cells in the hippocampus are dynamic and flexible, sensitive to the mnemonic and behavioral (not just spatial) requirements of a given task, which may suggest these neurons play a critical role in distinguishing primarily between contexts. Given that episodic memory necessarily requires spatial-temporal context, David Smith has thus argued in "The Hippocampus, Context Processing and Episodic Memory" (2008) that the primary function of the hippocampus may in fact be the encoding of context, which subsequently contributes this organized information to a broader circuit responsible for episodic memory.
Studies involving animals and human amnesiacs with damage localized to the hippocampus continue to be the primary subjects for investigations, although the development of optogenetics around 2005 has proven to be a groundbreaking methodological advancement. As opposed to the generalized targets of electrodes typically used in concert with functional magnetic resonance imaging (fMRI), optogenetics allows for specific neurons to be turned on and off by way of light fed through a fiber optic strand into the animal’s brain. The remarkable precision of this technology allows for the observation of individual neuronal activity as well as previously unknown neuronal connections, shedding light on the connection between hippocampal physiology and its behavioral ramifications. The use of optogenetics has thus provided insight into how the hippocampus connects to other parts of the brain, the plasticity of its networks, and the high degree of sensitivity exhibited in ensembles of hippocampal neurons as they fire in response to different contexts.
The ability to precisely manipulate select neurons has also aided understanding of adult neurogenesis (birth of new cells) in the hippocampus, although the function of these new brain cells remains unknown. While adult neurogenesis has been linked to learning and memory, the variety of behavioral impairments produced from its inhibition suggest a broader function, particularly involving stress response, emotion, attention, and prediction. The connections between the hippocampus and the amygdala (responsible for emotion) are not yet well understood, and because investigations have focused predominantly on the hippocampus’s mnemonic properties, this area of research remains as yet underdeveloped.
The connection between adult neurogenesis and hippocampal pathology is also particularly in need of further research. The hippocampus is a vulnerable structure that can be damaged by epilepsy, oxygen starvation, or encephalitis. In patients with Alzheimer’s disease, it is the hippocampus that is firstly and most severely affected, and chronic stress, post-traumatic stress disorder, chronic severe depression, and schizophrenia have all been linked with decreased hippocampal volume.
Bibliography
Anderson, Per, Richard Morris, David Amaral, Tim Biss, and John O’Keefe, editors. The Hippocampus Book. Oxford UP, 2007. Oxford Neuroscience Series.
Cameron, Heather A., and Lucas R. Glover. “Adult Neurogenesis: Beyond Learning and Memory.” Annual Review of Psychology, vol. 66, 2015, pp. 53–81.
Eichenbaum, H., M. Sauvage, N. Fortin, R. Komorowski, and P. Lipton. “Towards a Functional Organization of Episodic Memory in the Medial Temporal Lobe.” Neuroscience & Biobehavioral Reviews, vol. 36, no. 7, 2012, pp. 1597–1608.
Eichenbaum, H. “Time Cells in the Hippocampus: A New Dimension for Mapping Memories.” Nature Reviews Neuroscience, vol. 15, 2014, pp. 732–744.
Fogwe, Leslie A., et al. "Neuroanatomy, Hippocampus." StatPearls, NIH National Library of Medicine, 20 July 2023, www.ncbi.nlm.nih.gov/books/NBK482171/. Accessed 7 Nov. 2024.
Knierim, J. J. “From the GPS to HM: Place Cells, Grid Cells, and Memory.” Perspectives on 2014 Nobel Prize. Special issue of Hippocampus, vol. 25, no. 6, 2015, pp. 719–725.
Moser, E. I., E. Kropf, and M-B Moser. “Place Cells, Grid Cells, and the Brain’s Spatial Representation System.” Annual Review of Neuroscience, vol. 31, 2008, pp. 69–89.
O’Keefe, J., and L. Nadel. The Hippocampus as a Cognitive Map. Oxford UP, 1978.
Scoville, W. B., and B. Milner. “Loss of Recent Memory after Bilateral Hippocampal Lesions.” Journal of Neurology, Neurosurgery & Psychiatry, vol. 20, no. 1, 1957, pp. 11–21.
Smith, D. M. “The Hippocampus, Context Processing and Episodic Memory.” Handbook of Episodic Memory, edited by E. Dere, A. Easton, L. Nadel, and J. Huston, Elsevier, 2008, pp. 465–481.
Smith, D. M., and D. A. Bulkin. “The Form and Function of Hippocampal Context Representations.” Neuroscience & Biobehavioral Reviews, vol. 40, 2014, pp. 52–61.