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Robotic Brain Universe

The hippocampus and memory

How the brain records new memories and maps space, what patient H.M. revealed, and how AI navigators and memory implants learn from it.

Intermediate · about 9 min · updated 2026-10-02 · awaiting clinical review

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Illustrative simulation excitatory inhibitory

Patient H.M. and the medial temporal lobe; place cells, grid cells and the 2014 Nobel Prize; long-term potentiation, replay in sleep and complementary learning systems; taxi drivers, the adult neurogenesis debate and the forgetting curve; Alzheimer's staging, temporal lobe epilepsy surgery and amnesia; grid and place cell equations and associative memory; grid-like units in AI agents, the Tolman–Eichenbaum machine and a hippocampal memory prosthesis.

Contents
  1. Where memories begin
  2. What the hippocampus is
  3. Why a separate memory system
  4. How memories are stored
  5. When the hippocampus changes
  6. When memory fails
  7. The mathematics of memory and space
  8. Technology: AI navigators and memory prostheses
  9. Milestones
  10. Frontiers
  11. Check yourself

Where memories begin

In 1953 a young man known for decades only as H.M. had parts of both medial temporal lobes removed to control his seizures, and afterwards could no longer form lasting new memories. Studied for five decades until his death in December 2008, he is probably the best-known single patient in the history of neuroscience, and his case established fundamental principles of how memory is organised in the brain.[1,2]

The structure at the centre of his story, the hippocampus, is also the brain's map of space. Its place cells and the grid cells next door in the entorhinal cortex earned the 2014 Nobel Prize in Physiology or Medicine, 'for their discoveries of cells that constitute a positioning system in the brain'.[3,4,5]

Today AI agents trained to navigate develop grid-like units of their own, and an implant has improved human memory by stimulating the hippocampus with the patient's own firing patterns. This reading covers what the hippocampus does, how it stores memories, what happens when it fails, and the mathematics and technology of memory.[6,7]

What the hippocampus is

The hippocampus is a curled structure in the medial temporal lobe, part of the hippocampal formation that includes the dentate gyrus. Its main input arrives from the neighbouring entorhinal cortex through the perforant path, and inside it signals pass from the dentate gyrus through the CA3 and CA1 fields.[7,8,9,10]

It is needed to form new memories of facts and events. H.M.'s operation, which removed medial temporal structures on both sides, left a severe loss of recent memory; work with him showed that memory is a distinct brain function and that the medial temporal lobe is essential for forming long-term memories but not for holding information briefly or for older memories.[1,2,11]

Key numbers

Seizure-free (seizures impairing awareness) one year after temporal lobe surgery, versus medication
58% versus 8%[12]
Rabbits showing long-term potentiation after conditioning trains in the first LTP study
15 of 18[8]
Grid cells needed to form one place field in a model
about 10 to 50[9]
Improvement in short-term memory with hippocampal prosthetic stimulation
37%[7]

Why a separate memory system

Learning something new without wrecking what you already know is hard for any network (see Neural networks, biological and artificial). McClelland and colleagues proposed that the hippocampus learns new items quickly and then repeatedly reinstates them in the neocortex, which learns slowly and interleaves new memories with old ones. This explains why hippocampal damage disrupts recent memory but leaves remote memories intact.[11]

The hippocampus also gives memories a place. Place cells fire when an animal is in a particular location, and grid cells in the medial entorhinal cortex fire at the vertices of a triangular grid covering the whole environment, a metric for space that persists even when landmarks are removed.[4,5]

How memories are stored

Strengthened synapses. In 1973 Bliss and Lømo stimulated the perforant path, the input from entorhinal cortex to the dentate gyrus, in anaesthetised rabbits. Brief high-frequency trains made later responses larger for between 30 minutes and 10 hours: long-term potentiation, a form of the lasting synaptic change Hebb had proposed.[8,13]

Replay during sleep. Hippocampal place cells that fired together while rats explored tended to fire together again in the slow-wave sleep that followed, re-expressing the day's experience in a way that theories of consolidation predict.[14]

Maps from grids. Solstad, Moser and Einevoll showed that summing weighted input from 10 to 50 grid cells with similar phases but different orientations and spacings yields a single, confined place field, one way the entorhinal grid could build the hippocampal map.[9]

The hippocampal memory circuitNeocortexsights, sounds, factsEntorhinal cortexgrid cells; main inputDentate gyrusreached by the perforant pathCA3recurrent connectionsCA1place cells; outputReplay in sleepreinstates new memoriesperforant pathconsolidation
The hippocampal memory circuit. Information from the neocortex enters through the entorhinal cortex, passes through the hippocampal fields and is replayed, during sleep and rest, back to the neocortex, which slowly absorbs it.[5,7,8,11,14]
Text version of the diagram
  1. Neocortex: sights, sounds, facts. Leads to Entorhinal cortex.
  2. Entorhinal cortex: grid cells; main input. Leads to Dentate gyrus (perforant path).
  3. Dentate gyrus: reached by the perforant path. Leads to CA3.
  4. CA3: recurrent connections. Leads to CA1.
  5. CA1: place cells; output. Leads to Replay in sleep.
  6. Replay in sleep: reinstates new memories. Leads to Neocortex (consolidation).

When the hippocampus changes

With experience. London taxi drivers, who learn the city's streets in detail, had larger posterior hippocampi than controls, and the longer they had driven a taxi, the larger the posterior and the smaller the anterior hippocampus.[15]

New neurons, or not? Whether the adult human hippocampus keeps making neurons is debated. Labelling dividing cells showed new neurons in the dentate gyrus of adults in 1998, and a 2018 study of people aged 14 to 79 found thousands of immature neurons at every age; another 2018 study found that young neurons fall sharply in the first year of life and were undetectable in adults.[16,17,18]

Over time. Forgetting follows a lawful curve. Repeating Ebbinghaus's 1880 self-experiment, Murre and Dros found a very similar curve, with an upward jump starting at the 24-hour point.[19]

When memory fails

Alzheimer's disease. Neurofibrillary tangles spread in a characteristic order: first the transentorhinal region (stages I–II), then the entorhinal cortex and the first sector of Ammon's horn (stages III–IV), and finally almost all isocortical association areas (stages V–VI). The early stages therefore strike the gateway to the hippocampus.[10]

Epilepsy. The medial temporal lobe is a common source of seizures. In a randomised trial of 80 patients with temporal lobe epilepsy, 58% were free of seizures that impair awareness one year after surgery, against 8% with continued medication, and quality of life was better.[12]

Amnesia. Bilateral medial temporal damage, as in H.M., leaves a severe inability to form new long-term memories of facts and events.[1,2]

The mathematics of memory and space

Memory and navigation have elegant mathematical descriptions, from the curve of forgetting to the geometry of grid cells.[9,19]

Grid cell firing as three plane waves[5,9]
g(x)=∑k=13cos⁡ ⁣(kk⋅(x−c)),∣kk∣=4π3 λg(\mathbf{x}) = \sum_{k=1}^{3} \cos\!\left(\mathbf{k}_k \cdot (\mathbf{x} - \mathbf{c})\right), \qquad |\mathbf{k}_k| = \frac{4\pi}{\sqrt{3}\,\lambda}

Adding three cosine gratings whose directions are 60° apart gives peaks on a triangular grid, the pattern grid cells show. Changing the spacing λ\lambda, orientation and offset c\mathbf{c} gives the family of grids found in the entorhinal cortex.

Symbols in Grid cell firing as three plane waves
SymbolMeaningUnit
x\mathbf{x}the animal's positionm
kk\mathbf{k}_kwave vectors 60° apart—
λ\lambdagrid spacingm
c\mathbf{c}grid phase (offset)m
Place field from grid cells[9]
p(x)=[∑iwi gi(x)−θ]+p(\mathbf{x}) = \left[\sum_{i} w_i\, g_i(\mathbf{x}) - \theta\right]_{+}

A place cell's firing modelled as a weighted sum of grid-cell inputs; keeping only activity above a threshold isolates the strongest peak. With 10 to 50 grids of similar phase but different spacings and orientations, the peaks line up in only one place and a single confined place field emerges.

Symbols in Place field from grid cells
SymbolMeaningUnit
gig_ifiring of grid cell i—
wiw_isynaptic weight from grid cell i—
θ\thetathreshold—
[⋅]+[\cdot]_{+}keeps only positive values—
Associative memory (Hopfield energy)[13,20]
E=−12∑i≠jwij si sj,wij∝∑μξiμξjμE = -\tfrac{1}{2}\sum_{i \neq j} w_{ij}\, s_i\, s_j, \qquad w_{ij} \propto \sum_{\mu} \xi_i^{\mu}\xi_j^{\mu}

In a network with recurrent connections, storing patterns ξμ\xi^{\mu} with a Hebbian rule makes them energy minima, so a partial cue settles into the whole memory, the content-addressable recall Hopfield described.

Symbols in Associative memory (Hopfield energy)
SymbolMeaningUnit
sis_istate of unit i—
wijw_{ij}connection strength—
ξμ\xi^{\mu}stored pattern number μ—
Forgetting curve[19]
R(t)=e−t/SR(t) = e^{-t/S}

A simple description of retention decaying with time since learning; Murre and Dros compared several such equations against their replication of Ebbinghaus's data, which also showed a jump upwards at one day that a single smooth curve misses.

Symbols in Forgetting curve
SymbolMeaningUnit
RRproportion retained—
tttime since learningh
SSmemory stabilityh

Technology: AI navigators and memory prostheses

Grid cells in AI. Banino and colleagues trained a recurrent network to keep track of its position from its own movements (path integration). Grid-like units emerged, along with other entorhinal-like cell types, and an agent using them navigated to goals in unfamiliar, changing environments better than an expert human.[6]

A model of relational memory. The Tolman–Eichenbaum machine proposes that entorhinal cells form a basis describing the structure of the world and hippocampal cells bind it to sensory inputs. After learning, its units resemble grid, border and object-vector cells, and it predicted that hippocampal remapping preserves structure, which was confirmed in recordings.[21]

A memory prosthesis. Hampson and colleagues built a model of how CA3 and CA1 neurons fire when people successfully encode a memory, then stimulated CA1 with the predicted patterns. Short-term memory improved by 37%, and longer-term recognition of the images improved by 35%.[7]

Navigation in brains and machines[5,6,11,14,20,21]
BrainArtificial counterpart
Grid cells (entorhinal cortex)Grid-like units in a recurrent network trained on path integration
Place cells (hippocampus)Units binding structure to sensory input in the Tolman–Eichenbaum machine
Recalling a whole memory from a partHopfield associative memory
Replay during sleepInterleaved learning that avoids catastrophic forgetting

Milestones

Memory and the hippocampus

  1. 1957Scoville and Milner report H.M.'s loss of recent memory after bilateral medial temporal surgery.[1]
  2. 1971O'Keefe and Dostrovsky find hippocampal cells that signal place.[4]
  3. 1973Long-term potentiation is discovered in the hippocampus.[8]
  4. 1982Hopfield networks model content-addressable memory.[20]
  5. 1991The Braak stages describe how Alzheimer's pathology spreads from the entorhinal region.[10]
  6. 1994Place cells replay waking activity during sleep.[14]
  7. 1995The complementary learning systems theory.[11]
  8. 1998New neurons are found in the adult human dentate gyrus.[16]
  9. 2000Taxi drivers' posterior hippocampi are larger.[15]
  10. 2001Surgery beats medication for temporal lobe epilepsy in a randomised trial.[12]
  11. 2005Grid cells are discovered in the entorhinal cortex.[5]
  12. 2014Nobel Prize to O'Keefe, May-Britt Moser and Edvard Moser.[3]
  13. 2018Grid-like units emerge in an AI navigator; a hippocampal prosthesis improves human memory; the neurogenesis debate sharpens.[6,7,17,18]
  14. 2020The Tolman–Eichenbaum machine links spatial and relational memory.[21]

Frontiers

Space may be one case of a general code. The Tolman–Eichenbaum machine treats spatial and relational memory alike, and its model cells aligned with recorded representations in complex non-spatial tasks as well as in navigation.[21]

Memory prostheses are moving from non-specific stimulation to stimulation shaped by the person's own neural code, using models that predict the activity of CA1 neurons during successful encoding.[7]

Check yourself

Check yourself

  1. What did patient H.M. teach us about memory?
    Show answer

    That the medial temporal lobe, including the hippocampus, is essential for forming new long-term memories of facts and events, and that memory is a distinct brain function.

  2. What is the difference between place cells and grid cells?
    Show answer

    Place cells fire in one location; grid cells fire at the vertices of a triangular grid covering the whole environment.

  3. What is long-term potentiation and where was it first shown?
    Show answer

    A lasting increase in synaptic strength after high-frequency stimulation, first shown at the perforant path to dentate gyrus synapse of the rabbit hippocampus.

  4. Why might the brain need both a fast hippocampus and a slow neocortex?
    Show answer

    So new items can be learned quickly without overwriting the structure of old knowledge, which the neocortex absorbs gradually through interleaved replay.

  5. Which region do the earliest Braak stages of Alzheimer's disease affect?
    Show answer

    The transentorhinal region, then the entorhinal cortex, the gateway to the hippocampus.

  6. What emerged when a recurrent network was trained on path integration?
    Show answer

    Grid-like units, along with other entorhinal-like cell types.

  7. How did the hippocampal memory prosthesis work?
    Show answer

    It modelled CA3 and CA1 firing during successful encoding and stimulated CA1 with the predicted patterns, improving memory.

Glossary[2,4,5,6,8,14]

Hippocampus
A curled medial temporal lobe structure essential for forming new memories and for spatial maps.
Entorhinal cortex
Cortex next to the hippocampus that provides its main input and contains grid cells.
Dentate gyrus
The first hippocampal stage, receiving the perforant path.
Place cell
A hippocampal neuron that fires when an animal is in a particular location.
Grid cell
An entorhinal neuron that fires at the vertices of a triangular grid across space.
Long-term potentiation
A lasting strengthening of synapses after high-frequency activity.
Consolidation
The stabilisation of memories over time, partly through replay.
Path integration
Keeping track of position from one's own movements.
Amnesia
Loss of the ability to form or recall memories.
Neurogenesis
The birth of new neurons.

References

  1. Scoville WB, Milner B. Loss of recent memory after bilateral hippocampal lesions. Journal of Neurology, Neurosurgery and Psychiatry 1957;20(1):11-21. doi:10.1136/jnnp.20.1.11
  2. Squire LR. The legacy of patient H.M. for neuroscience. Neuron 2009;61(1):6-9. doi:10.1016/j.neuron.2008.12.023
  3. Nobel Prize Outreach. The Nobel Prize in Physiology or Medicine 2014. NobelPrize.org 2014. https://www.nobelprize.org/prizes/medicine/2014/summary/
  4. O'Keefe J, Dostrovsky J. The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. Brain Research 1971;34(1):171-175. doi:10.1016/0006-8993(71)90358-1
  5. Hafting T, Fyhn M, Molden S, Moser MB, Moser EI. Microstructure of a spatial map in the entorhinal cortex. Nature 2005;436(7052):801-806. doi:10.1038/nature03721
  6. Banino A, Barry C, Uria B, Blundell C, Lillicrap T, Mirowski P, et al.. Vector-based navigation using grid-like representations in artificial agents. Nature 2018;557(7705):429-433. doi:10.1038/s41586-018-0102-6
  7. Hampson RE, Song D, Robinson BS, Fetterhoff D, Dakos AS, Roeder BM, et al.. Developing a hippocampal neural prosthetic to facilitate human memory encoding and recall. Journal of Neural Engineering 2018;15(3):036014. doi:10.1088/1741-2552/aaaed7
  8. Bliss TVP, Lømo T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. The Journal of Physiology 1973;232(2):331-356. doi:10.1113/jphysiol.1973.sp010273
  9. Solstad T, Moser EI, Einevoll GT. From grid cells to place cells: a mathematical model. Hippocampus 2006;16(12):1026-1031. doi:10.1002/hipo.20244
  10. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathologica 1991;82(4):239-259. doi:10.1007/BF00308809
  11. McClelland JL, McNaughton BL, O'Reilly RC. Why there are complementary learning systems in the hippocampus and neocortex: insights from the successes and failures of connectionist models of learning and memory. Psychological Review 1995;102(3):419-457. doi:10.1037/0033-295X.102.3.419
  12. Wiebe S, Blume WT, Girvin JP, Eliasziw M. A randomized, controlled trial of surgery for temporal-lobe epilepsy. New England Journal of Medicine 2001;345(5):311-318. doi:10.1056/NEJM200108023450501
  13. Hebb DO. The Organization of Behavior. Psychology Press 2005. doi:10.4324/9781410612403
  14. Wilson MA, McNaughton BL. Reactivation of hippocampal ensemble memories during sleep. Science 1994;265(5172):676-679. doi:10.1126/science.8036517
  15. Maguire EA, Gadian DG, Johnsrude IS, Good CD, Ashburner J, Frackowiak RSJ, Frith CD. Navigation-related structural change in the hippocampi of taxi drivers. Proceedings of the National Academy of Sciences of the USA 2000;97(8):4398-4403. doi:10.1073/pnas.070039597
  16. Eriksson PS, Perfilieva E, Björk-Eriksson T, Alborn AM, Nordborg C, Peterson DA, Gage FH. Neurogenesis in the adult human hippocampus. Nature Medicine 1998;4(11):1313-1317. doi:10.1038/3305
  17. Boldrini M, Fulmore CA, Tartt AN, Simeon LR, Pavlova I, Poposka V, et al.. Human hippocampal neurogenesis persists throughout aging. Cell Stem Cell 2018;22(4):589-599.e5. doi:10.1016/j.stem.2018.03.015
  18. Sorrells SF, Paredes MF, Cebrian-Silla A, Sandoval K, Qi D, Kelley KW, et al.. Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature 2018;555(7696):377-381. doi:10.1038/nature25975
  19. Murre JMJ, Dros J. Replication and analysis of Ebbinghaus' forgetting curve. PLoS ONE 2015;10(7):e0120644. doi:10.1371/journal.pone.0120644
  20. Hopfield JJ. Neural networks and physical systems with emergent collective computational abilities. Proceedings of the National Academy of Sciences of the USA 1982;79(8):2554-2558. doi:10.1073/pnas.79.8.2554
  21. Whittington JCR, Muller TH, Mark S, Chen G, Barry C, Burgess N, Behrens TEJ. The Tolman-Eichenbaum machine: unifying space and relational memory through generalization in the hippocampal formation. Cell 2020;183(5):1249-1263.e23. doi:10.1016/j.cell.2020.10.024

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Template anatomy for education. Not patient-specific. Not for clinical decision-making.