Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perspective
  • Published:

Assessments of dentate gyrus function: discoveries and debates

Abstract

There has been considerable speculation regarding the function of the dentate gyrus (DG) — a subregion of the mammalian hippocampus — in learning and memory. In this Perspective article, we compare leading theories of DG function. We note that these theories all critically rely on the generation of distinct patterns of activity in the region to signal differences between experiences and to reduce interference between memories. However, these theories are divided by the roles they attribute to the DG during learning and recall and by the contributions they ascribe to specific inputs or cell types within the DG. These differences influence the information that the DG is thought to impart to downstream structures. We work towards a holistic view of the role of DG in learning and memory by first developing three critical questions to foster a dialogue between the leading theories. We then evaluate the extent to which previous studies address our questions, highlight remaining areas of conflict, and suggest future experiments to bridge these theories.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Schematic of mechanisms driving each proposed theory of dentate gyrus function.
Fig. 2: Leading theory compatibility.

Similar content being viewed by others

References

  1. Amaral, D. G., Scharfman, H. E. & Lavenex, P. The dentate gyrus: fundamental neuroanatomical organization (dentate gyrus for dummies). Prog. Brain Res. 163, 3–22 (2007).

    PubMed  PubMed Central  Google Scholar 

  2. Cameron, H., Woolley, C., McEwen, B. & Gould, E. Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat. Neuroscience 56, 337–344 (1993).

    CAS  PubMed  Google Scholar 

  3. Eriksson, P. S. et al. Neurogenesis in the adult human hippocampus. Nat. Med. 4, 1313–1317 (1998).

    CAS  PubMed  Google Scholar 

  4. Kuhn, H. G., Toda, T. & Gage, F. H. Adult hippocampal neurogenesis: a coming-of-age story. J. Neurosci. 38, 10401–10410 (2018).

    PubMed  PubMed Central  Google Scholar 

  5. Paredes, M. F. et al. Does adult neurogenesis persist in the human hippocampus? Cell Stem Cell 23, 780–781 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Kempermann, G. et al. Human adult neurogenesis: evidence and remaining questions. Cell Stem Cell 23, 25–30 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Ohara, S. et al. Local projections of layer Vb-to-Va are more prominent in lateral than in medial entorhinal cortex. eLife 10, e67262 (2021).

    CAS  Google Scholar 

  8. Ming, G. & Song, H. Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 70, 687–702 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Marr, D. A theory of cerebellar cortex. J. Physiol. 202, 437–470 (1969).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Eccles, J., Ito, M. & Szentagothai, J. The Cerebellum as a Neuronal Machine 335 (Springer, 1967).

  11. Rolls, E. T. in Neural Models of Plasticity 240–265 (Elsevier, 1989).

  12. McNaughton, B. L. & Morris, R. G. Hippocampal synaptic enhancement and information storage within a distributed memory system. Trends Neurosci. 10, 408–415 (1987).

    Google Scholar 

  13. McNaughton, B. L. & Nadel, L. in Neuroscience and Connectionist Theory (eds Gluck, M. A. & Rumelhart, D. E.) 1–63 (Lawrence Erlbaum, 1990).

  14. O’reilly, R. C. & McClelland, J. L. Hippocampal conjunctive encoding, storage, and recall: avoiding a trade‐off. Hippocampus 4, 661–682 (1994).

    PubMed  Google Scholar 

  15. Myers, C. E. & Scharfman, H. E. Pattern separation in the dentate gyrus: a role for the CA3 backprojection. Hippocampus 21, 1190–1215 (2011).

    PubMed  Google Scholar 

  16. Myers, C. E. & Scharfman, H. E. A role for hilar cells in pattern separation in the dentate gyrus: a computational approach. Hippocampus 19, 321–337 (2009).

    PubMed  PubMed Central  Google Scholar 

  17. Amaral, D., Ishizuka, N. & Claiborne, B. Neurons, numbers and the hippocampal network. Prog. Brain Res. 83, 1–11 (1990).

    CAS  PubMed  Google Scholar 

  18. Yassa, M. A. & Stark, C. E. Pattern separation in the hippocampus. Trends Neurosci. 34, 515–525 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Mishkin, M., Suzuki, W. A., Gadian, D. G. & Vargha-Khadem, F. Hierarchical organization of cognitive memory. Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci. 352, 1461–1467 (1997).

    CAS  Google Scholar 

  20. Manns, J. R. & Eichenbaum, H. Evolution of declarative memory. Hippocampus 16, 795–808 (2006).

    PubMed  Google Scholar 

  21. Knierim, J. J., Lee, I. & Hargreaves, E. L. Hippocampal place cells: parallel input streams, subregional processing, and implications for episodic memory. Hippocampus 16, 755–764 (2006).

    PubMed  Google Scholar 

  22. Reagh, Z. M. & Yassa, M. A. Object and spatial mnemonic interference differentially engage lateral and medial entorhinal cortex in humans. Proc. Natl Acad. Sci. USA 111, E4264–E4273 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Doan, T. P., Lagartos-Donate, M. J., Nilssen, E. S., Ohara, S. & Witter, M. P. Convergent projections from perirhinal and postrhinal cortices suggest a multisensory nature of lateral, but not medial, entorhinal cortex. Cell Rep. 29, 617–627 (2019).

    CAS  PubMed  Google Scholar 

  24. Nilssen, E. S., Doan, T. P., Nigro, M. J., Ohara, S. & Witter, M. P. Neurons and networks in the entorhinal cortex: a reappraisal of the lateral and medial entorhinal subdivisions mediating parallel cortical pathways. Hippocampus 29, 1238–1254 (2019).

    CAS  PubMed  Google Scholar 

  25. Burwell, R. D. & Amaral, D. G. Perirhinal and postrhinal cortices of the rat: interconnectivity and connections with the entorhinal cortex. J. Comp. Neurol. 391, 293–321 (1998).

    CAS  PubMed  Google Scholar 

  26. Knierim, J. J., Neunuebel, J. P. & Deshmukh, S. S. Functional correlates of the lateral and medial entorhinal cortex: objects, path integration and local–global reference frames. Philos. Trans. R. Soc. B Biol. Sci. 369, 20130369 (2014).

    Google Scholar 

  27. Neunuebel, J. P., Yoganarasimha, D., Rao, G. & Knierim, J. J. Conflicts between local and global spatial frameworks dissociate neural representations of the lateral and medial entorhinal cortex. J. Neurosci. 33, 9246–9258 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. O’Keefe, J. O. & Nadel, L. The Hippocampus as a Cognitive Map (Clarendon, 1978).

  29. O’Keefe, J. & Nadel, L. Précis of O’Keefe & Nadel’s The hippocampus as a cognitive map. Behav. Brain Sci. 2, 487–494 (1979).

    Google Scholar 

  30. Rueckemann, J. W., Sosa, M., Giocomo, L. M. & Buffalo, E. A. The grid code for ordered experience. Nat. Rev. Neurosci. 22, 637–649 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Lee, J. W. & Jung, M. W. Separation or binding? Role of the dentate gyrus in hippocampal mnemonic processing. Neurosci. Biobehav. Rev. 75, 183–194 (2017).

    PubMed  Google Scholar 

  32. Vinogradova, O. The hippocampus and the orienting reflex. Neuronal Mech. Orient. Reflex. 128, 154 (1975).

    Google Scholar 

  33. Amaral, D. G. & Campbell, M. Transmitter systems in the primate dentate gyrus. Hum. Neurobiol. 5, 169–180 (1986).

    CAS  PubMed  Google Scholar 

  34. Prince, L. Y., Bacon, T. J., Tigaret, C. M. & Mellor, J. R. Neuromodulation of the feedforward dentate gyrus-CA3 microcircuit. Front. Synaptic Neurosci. 8, 32 (2016).

    PubMed  PubMed Central  Google Scholar 

  35. Harley, C. W. Norepinephrine and the dentate gyrus. Prog. Brain Res. 163, 299–318 (2007).

    CAS  PubMed  Google Scholar 

  36. Straube, T., Korz, V., Balschun, D. & Uta Frey, J. Requirement of β‐adrenergic receptor activation and protein synthesis for LTP‐reinforcement by novelty in rat dentate gyrus. J. Physiol. 552, 953–960 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Brown, R. A., Walling, S. G., Milway, J. S. & Harley, C. W. Locus ceruleus activation suppresses feedforward interneurons and reduces β-γ electroencephalogram frequencies while it enhances θ frequencies in rat dentate gyrus. J. Neurosci. 25, 1985–1991 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Kitchigina, V., Vankov, A., Harley, C. & Sara, S. J. Novelty‐elicited, noradrenaline‐dependent enhancement of excitability in the dentate gyrus. Eur. J. Neurosci. 9, 41–47 (1997).

    CAS  PubMed  Google Scholar 

  39. Ogando, M. B. et al. Cholinergic modulation of dentate gyrus processing through dynamic reconfiguration of inhibitory circuits. Cell Rep. 36, 109572 (2021).

    CAS  PubMed  Google Scholar 

  40. Hofmann, M. E. & Frazier, C. J. Muscarinic receptor activation modulates the excitability of hilar mossy cells through the induction of an afterdepolarization. Brain Res. 1318, 42–51 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Duffy, A. M., Schaner, M. J., Chin, J. & Scharfman, H. E. Expression of c‐fos in hilar mossy cells of the dentate gyrus in vivo. Hippocampus 23, 649–655 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Bernstein, H. L., Lu, Y.-L., Botterill, J. J. & Scharfman, H. E. Novelty and novel objects increase c-Fos immunoreactivity in mossy cells in the mouse dentate gyrus. Neural Plast. https://doi.org/10.1155/2019/1815371 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Ewell, L. A. & Jones, M. V. Frequency-tuned distribution of inhibition in the dentate gyrus. J. Neurosci. 30, 12597–12607 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Buzsàki, G. & Eidelberg, E. Commissural projection to the dentate gyrus of the rat: evidence for feed-forward inhibition. Brain Res. 230, 346–350 (1981).

    PubMed  Google Scholar 

  45. Li, Y. et al. Molecular layer perforant path-associated cells contribute to feed-forward inhibition in the adult dentate gyrus. Proc. Natl Acad. Sci. USA 110, 9106–9111 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Sloviter, R. & Brisman, J. Lateral inhibition and granule cell synchrony in the rat hippocampal dentate gyrus. J. Neurosci. 15, 811–820 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Scharfman, H. E. Electrophysiological evidence that dentate hilar mossy cells are excitatory and innervate both granule cells and interneurons. J. Neurophysiol. 74, 179–194 (1995).

    CAS  PubMed  Google Scholar 

  48. Scharfman, H., Kunkel, D. & Schwartzkroin, P. A. Synaptic connections of dentate granule cells and hilar neurons: results of paired intracellular recordings and intracellular horseradish peroxidase injections. Neuroscience 37, 693–707 (1990).

    CAS  PubMed  Google Scholar 

  49. Otis, T. & Mody, I. Modulation of decay kinetics and frequency of GABAA receptor-mediated spontaneous inhibitory postsynaptic currents in hippocampal neurons. Neuroscience 49, 13–32 (1992).

    CAS  PubMed  Google Scholar 

  50. Staley, K. J., Otis, T. S. & Mody, I. Membrane properties of dentate gyrus granule cells: comparison of sharp microelectrode and whole-cell recordings. J. Neurophysiol. 67, 1346–1358 (1992).

    CAS  PubMed  Google Scholar 

  51. Espinoza, C., Guzman, S. J., Zhang, X. & Jonas, P. Parvalbumin + interneurons obey unique connectivity rules and establish a powerful lateral-inhibition microcircuit in dentate gyrus. Nat. Commun. 9, 4605 (2018).

    PubMed  PubMed Central  Google Scholar 

  52. Hsu, D. The dentate gyrus as a filter or gate: a look back and a look ahead. Prog. Brain Res. 163, 601–613 (2007).

    PubMed  Google Scholar 

  53. Josselyn, S. A., Köhler, S. & Frankland, P. W. Finding the engram. Nat. Rev. Neurosci. 16, 521–534 (2015).

    CAS  PubMed  Google Scholar 

  54. Hainmueller, T. & Bartos, M. Dentate gyrus circuits for encoding, retrieval and discrimination of episodic memories. Nat. Rev. Neurosci. 21, 153–168 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Sun, X. et al. Functionally distinct neuronal ensembles within the memory engram. Cell 181, 410–423 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Ramirez, S. et al. Activating positive memory engrams suppresses depression-like behaviour. Nature 522, 335–339 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Lacagnina, A. F. et al. Distinct hippocampal engrams control extinction and relapse of fear memory. Nat. Neurosci. 22, 753–761 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Denny, C. A., Lebois, E. & Ramirez, S. From engrams to pathologies of the brain. Front. Neural Circuits 11, 23 (2017).

    PubMed  PubMed Central  Google Scholar 

  59. Teyler, T. J. & DiScenna, P. The hippocampal memory indexing theory. Behav. Neurosci. 100, 147 (1986).

    CAS  PubMed  Google Scholar 

  60. Miller, S. M. & Sahay, A. Functions of adult-born neurons in hippocampal memory interference and indexing. Nat. Neurosci. 22, 1565–1575 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Piatti, V. C., Espósito, M. S. & Schinder, A. F. The timing of neuronal development in adult hippocampal neurogenesis. Neuroscientist 12, 463–468 (2006).

    CAS  PubMed  Google Scholar 

  62. Espósito, M. S. et al. Neuronal differentiation in the adult hippocampus recapitulates embryonic development. J. Neurosci. 25, 10074–10086 (2005).

    PubMed  PubMed Central  Google Scholar 

  63. Schmidt-Hieber, C., Jonas, P. & Bischofberger, J. Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature 429, 184–187 (2004).

    CAS  PubMed  Google Scholar 

  64. Gu, Y. et al. Optical controlling reveals time-dependent roles for adult-born dentate granule cells. Nat. Neurosci. 15, 1700–1706 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Tashiro, A., Makino, H. & Gage, F. H. Experience-specific functional modification of the dentate gyrus through adult neurogenesis: a critical period during an immature stage. J. Neurosci. 27, 3252–3259 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Rangel, L. et al. Temporally selective contextual encoding in the dentate gyrus of the hippocampus. Nat. Commun. 5, 3181 (2014).

    CAS  PubMed  Google Scholar 

  67. Park, S.-B. et al. The fasciola cinereum subregion of the hippocampus is important for the acquisition of visual contextual memory. Prog. Neurobiol. 210, 102217 (2022).

    PubMed  Google Scholar 

  68. Mau, W., Hasselmo, M. E. & Cai, D. J. The brain in motion: how ensemble fluidity drives memory-updating and flexibility. eLife 9, e63550 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Aimone, J. B., Wiles, J. & Gage, F. H. Potential role for adult neurogenesis in the encoding of time in new memories. Nat. Neurosci. 9, 723–727 (2006).

    CAS  PubMed  Google Scholar 

  70. Aimone, J. B., Wiles, J. & Gage, F. H. Computational influence of adult neurogenesis on memory encoding. Neuron 61, 187–202 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Lisman, J. E. Relating hippocampal circuitry to function: recall of memory sequences by reciprocal dentate–CA3 interactions. Neuron 22, 233–242 (1999).

    CAS  PubMed  Google Scholar 

  72. Aimone, J. B., Deng, W. & Gage, F. H. Resolving new memories: a critical look at the dentate gyrus, adult neurogenesis, and pattern separation. Neuron 70, 589–596 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Nolan, C. R., Wyeth, G., Milford, M. & Wiles, J. The race to learn: spike timing and STDP can coordinate learning and recall in CA3. Hippocampus 21, 647–660 (2011).

    PubMed  Google Scholar 

  74. Legéndy, C. R. On the ‘data stirring’ role of the dentate gyrus of the hippocampus. Rev. Neurosci. 28, 599–615 (2017).

    PubMed  Google Scholar 

  75. Sahay, A. & Hen, R. Adult hippocampal neurogenesis in depression. Nat. Neurosci. 10, 1110–1115 (2007).

    CAS  PubMed  Google Scholar 

  76. Cayco-Gajic, N. A. & Silver, R. A. Re-evaluating circuit mechanisms underlying pattern separation. Neuron 101, 584–602 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Hamlyn, L. Electron microscopy of mossy fibre endings in Ammon’s horn. Nature 190, 645–646 (1961).

    CAS  PubMed  Google Scholar 

  78. Chicurel, M. E. & Harris, K. M. Three‐dimensional analysis of the structure and composition of CA3 branched dendritic spines and their synaptic relationships with mossy fiber boutons in the rat hippocampus. J. Comp. Neurol. 325, 169–182 (1992).

    CAS  PubMed  Google Scholar 

  79. Rollenhagen, A. et al. Structural determinants of transmission at large hippocampal mossy fiber synapses. J. Neurosci. 27, 10434–10444 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Laatsch, R. H. & Cowan, W. Electron microscopic studies of the dentate gyrus of the rat. I. Normal structure with special reference to synaptic organization. J. Comp. Neurol. 128, 359–395 (1966).

    CAS  PubMed  Google Scholar 

  81. Henze, D. A., Wittner, L. & Buzsáki, G. Single granule cells reliably discharge targets in the hippocampal CA3 network in vivo. Nat. Neurosci. 5, 790–795 (2002).

    CAS  PubMed  Google Scholar 

  82. Scharfman, H. E. The neurobiology of epilepsy. Curr. Neurol. Neurosci. Rep. 7, 348–354 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Treves, A. & Rolls, E. T. Computational constraints suggest the need for two distinct input systems to the hippocampal CA3 network. Hippocampus 2, 189–199 (1992).

    CAS  PubMed  Google Scholar 

  84. Marr, D. Simple memory: a theory for archicortex. Philos. Trans. R. Soc. Lond. B Biol. Sci. 262, 23–81 (1971).

    CAS  PubMed  Google Scholar 

  85. Cerasti, E. & Treves, A. How informative are spatial CA3 representations established by the dentate gyrus? PLoS Computat. Biol. 6, e1000759 (2010).

    Google Scholar 

  86. McClelland, J. L., McNaughton, B. L. & O’Reilly, R. C. Why there are complementary learning systems in the hippocampus and neocortex: insights from the successes and failures of connectionist models of learning and memory. Psychol. Rev. 102, 419 (1995).

    PubMed  Google Scholar 

  87. O’Reilly, R. C., Bhattacharyya, R., Howard, M. D. & Ketz, N. Complementary learning systems. Cogn. Sci. 38, 1229–1248 (2014).

    PubMed  Google Scholar 

  88. Lee, H., GoodSmith, D. & Knierim, J. J. Parallel processing streams in the hippocampus. Curr. Opin. Neurobiol. 64, 127–134 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Jarrard, L. E., Okaichi, H., Steward, O. & Goldschmidt, R. B. On the role of hippocampal connections in the performance of place and cue tasks: comparisons with damage to hippocampus. Behav. Neurosci. 98, 946 (1984).

    CAS  PubMed  Google Scholar 

  90. McLamb, R. L., Mundy, W. R. & Tilson, H. A. Intradentate colchicine impairs acquisition of a two-way active avoidance response in a Y-maze. Neurosci. Lett. 94, 338–342 (1988).

    CAS  PubMed  Google Scholar 

  91. Mcnaughton, B. L., Barnes, C. A., Meltzer, J. & Sutherland, R. Hippocampal granule cells are necessary for normal spatial learning but not for spatially-selective pyramidal cell discharge. Exp. Brain Res. 76, 485–496 (1989).

    CAS  PubMed  Google Scholar 

  92. Nanry, K. P., Mundy, W. R. & Tilson, H. A. Colchicine-induced alterations of reference memory in rats: role of spatial versus non-spatial task components. Behav. Brain Res. 35, 45–53 (1989).

    CAS  PubMed  Google Scholar 

  93. Xavier, G. F., Oliveira‐Filho, F. J. & Santos, A. M. Dentate gyrus‐selective colchicine lesion and disruption of performance in spatial tasks: difficulties in ‘place strategy’ because of a lack of flexibility in the use of environmental cues? Hippocampus 9, 668–681 (1999).

    CAS  PubMed  Google Scholar 

  94. Gilbert, P. E., Kesner, R. P. & Lee, I. Dissociating hippocampal subregions: a double dissociation between dentate gyrus and CA1. Hippocampus 11, 626–636 (2001).

    CAS  PubMed  Google Scholar 

  95. Lee, I. & Kesner, R. P. Differential roles of dorsal hippocampal subregions in spatial working memory with short versus intermediate delay. Behav. Neurosci. 117, 1044 (2003).

    PubMed  Google Scholar 

  96. Lee, I. & Kesner, R. P. Encoding versus retrieval of spatial memory: double dissociation between the dentate gyrus and the perforant path inputs into CA3 in the dorsal hippocampus. Hippocampus 14, 66–76 (2004).

    PubMed  Google Scholar 

  97. Lee, I. & Kesner, R. P. Differential contributions of dorsal hippocampal subregions to memory acquisition and retrieval in contextual fear‐conditioning. Hippocampus 14, 301–310 (2004).

    PubMed  Google Scholar 

  98. Lee, I., Hunsaker, M. R. & Kesner, R. P. The role of hippocampal subregions in detecting spatial novelty. Behav. Neurosci. 119, 145 (2005).

    PubMed  Google Scholar 

  99. Hernández-Rabaza, V. et al. The hippocampal dentate gyrus is essential for generating contextual memories of fear and drug-induced reward. Neurobiol. Learn. Mem. 90, 553–559 (2008).

    PubMed  Google Scholar 

  100. Lee, C.-H. & Lee, I. Impairment of pattern separation of ambiguous scenes by single units in the CA3 in the absence of the dentate gyrus. J. Neurosci. 40, 3576–3590 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Lee, I. & Solivan, F. The roles of the medial prefrontal cortex and hippocampus in a spatial paired-association task. Learn. Mem. 15, 357–367 (2008).

    PubMed  PubMed Central  Google Scholar 

  102. Ahn, J. & Lee, I. Intact CA3 in the hippocampus is only sufficient for contextual behavior based on well‐learned and unaltered visual background. Hippocampus 24, 1081–1093 (2014).

    PubMed  Google Scholar 

  103. Walsh, T. J., Schulz, D. W., Tilson, H. A. & Schmechel, D. E. Cochicine-induced granule cell loss in rat hippocampus: selective behavioral and histological alterations. Brain Res. 398, 23–36 (1986).

    CAS  PubMed  Google Scholar 

  104. Bernier, B. E. et al. Dentate gyrus contributes to retrieval as well as encoding: evidence from context fear conditioning, recall, and extinction. J. Neurosci. 37, 6359–6371 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Lassalle, J.-M., Bataille, T. & Halley, H. Reversible inactivation of the hippocampal mossy fiber synapses in mice impairs spatial learning, but neither consolidation nor memory retrieval, in the Morris navigation task. Neurobiol. Learn. Mem. 73, 243–257 (2000).

    CAS  PubMed  Google Scholar 

  106. Madroñal, N. et al. Rapid erasure of hippocampal memory following inhibition of dentate gyrus granule cells. Nat. Commun. 7, 10923 (2016).

    Google Scholar 

  107. Lee, I. & Solivan, F. Dentate gyrus is necessary for disambiguating similar object-place representations. Learn. Mem. 17, 252–258 (2010).

    PubMed  PubMed Central  Google Scholar 

  108. O’Keefe, J. & Dostrovsky, J. The hippocampus as a spatial map: preliminary evidence from unit activity in the freely-moving rat. Brain Res. 34, 171–175 (1971).

    PubMed  Google Scholar 

  109. Eichenbaum, H., Dudchenko, P., Wood, E., Shapiro, M. & Tanila, H. The hippocampus, memory, and place cells: is it spatial memory or a memory space? Neuron 23, 209–226 (1999).

    CAS  PubMed  Google Scholar 

  110. van Dijk, M. T. & Fenton, A. A. On how the dentate gyrus contributes to memory discrimination. Neuron 98, 832–845 (2018).

    PubMed  PubMed Central  Google Scholar 

  111. Senzai, Y. & Buzsáki, G. Physiological properties and behavioral correlates of hippocampal granule cells and mossy cells. Neuron 93, 691–704 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  112. GoodSmith, D. et al. Spatial representations of granule cells and mossy cells of the dentate gyrus. Neuron 93, 677–690 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Knierim, J. J. & Neunuebel, J. P. Tracking the flow of hippocampal computation: pattern separation, pattern completion, and attractor dynamics. Neurobiol. Learn. Mem. 129, 38–49 (2016).

    CAS  PubMed  Google Scholar 

  114. GoodSmith, D., Lee, H., Neunuebel, J. P., Song, H. & Knierim, J. J. Dentate gyrus mossy cells share a role in pattern separation with dentate granule cells and proximal CA3 pyramidal cells. J. Neurosci. 39, 9570–9584 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Neunuebel, J. P. & Knierim, J. J. CA3 retrieves coherent representations from degraded input: direct evidence for CA3 pattern completion and dentate gyrus pattern separation. Neuron 81, 416–427 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Neunuebel, J. P. & Knierim, J. J. Spatial firing correlates of physiologically distinct cell types of the rat dentate gyrus. J. Neurosci. 32, 3848–3858 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Hainmueller, T. & Bartos, M. Parallel emergence of stable and dynamic memory engrams in the hippocampus. Nature 558, 292–296 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Jung, D. et al. Dentate granule and mossy cells exhibit distinct spatiotemporal responses to local change in a one-dimensional landscape of visual-tactile cues. Sci. Rep. 9, 9545 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Fredes, F. & Shigemoto, R. The role of hippocampal mossy cells in novelty detection. Neurobiol. Learn. Mem. 183, 107486 (2021).

    PubMed  Google Scholar 

  120. Fredes, F. et al. Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation. Curr. Biol. 31, 25–38 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Kirschen, G. W. et al. Active dentate granule cells encode experience to promote the addition of adult-born hippocampal neurons. J. Neurosci. 37, 4661–4678 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Kim, S., Jung, D. & Royer, S. Place cell maps slowly develop via competitive learning and conjunctive coding in the dentate gyrus. Nat. Commun. 11, 4550 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Woods, N. I. et al. The dentate gyrus classifies cortical representations of learned stimuli. Neuron 107, 173–184 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Ramirez, S. et al. Creating a false memory in the hippocampus. Science 341, 387–391 (2013).

    CAS  PubMed  Google Scholar 

  125. Guo, N. et al. Dentate granule cell recruitment of feedforward inhibition governs engram maintenance and remote memory generalization. Nat. Med. 24, 438–449 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Liu, X. et al. Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature 484, 381–385 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Kitamura, T. et al. Engrams and circuits crucial for systems consolidation of a memory. Science 356, 73–78 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Josselyn, S. A. & Tonegawa, S. Memory engrams: recalling the past and imagining the future. Science 367, eaaw4325 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Guskjolen, A. et al. Recovery of ‘lost’ infant memories in mice. Curr. Biol. 28, 2283–2290 (2018).

    CAS  PubMed  Google Scholar 

  130. Ryan, T. J., Roy, D. S., Pignatelli, M., Arons, A. & Tonegawa, S. Engram cells retain memory under retrograde amnesia. Science 348, 1007–1013 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Denny, C. A. et al. Hippocampal memory traces are differentially modulated by experience, time, and adult neurogenesis. Neuron 83, 189–201 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Richards, B. A. & Frankland, P. W. The conjunctive trace. Hippocampus 23, 207–212 (2013).

    PubMed  Google Scholar 

  133. Routtenberg, A. Lifetime memories from persistently supple synapses. Hippocampus 23, 202–206 (2013).

    PubMed  Google Scholar 

  134. Stark, C. E. & Okado, Y. Making memories without trying: medial temporal lobe activity associated with incidental memory formation during recognition. J. Neurosci. 23, 6748–6753 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Guzman, S. J. et al. How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network. Nat. Comput. Sci. 1, 830–842 (2021).

    Google Scholar 

  136. Chambers, R. A., Potenza, M. N., Hoffman, R. E. & Miranker, W. Simulated apoptosis/neurogenesis regulates learning and memory capabilities of adaptive neural networks. Neuropsychopharmacology 29, 747–758 (2004).

    PubMed  Google Scholar 

  137. Becker, S. A computational principle for hippocampal learning and neurogenesis. Hippocampus 15, 722–738 (2005).

    PubMed  Google Scholar 

  138. Wiskott, L., Rasch, M. J., & Kempermann, G. A functional hypothesis for adult hippocampal neurogenesis: avoidance of catastrophic interference in the dentate gyrus. Hippocampus 16, 329–343 (2006).

    PubMed  Google Scholar 

  139. Deisseroth, K. et al. Excitation–neurogenesis coupling in adult neural stem/progenitor cells. Neuron 42, 535–552 (2004).

    CAS  PubMed  Google Scholar 

  140. Weisz, V. I. & Argibay, P. F. Neurogenesis interferes with the retrieval of remote memories: forgetting in neurocomputational terms. Cognition 125, 13–25 (2012).

    PubMed  Google Scholar 

  141. Tran, L. M., Josselyn, S. A., Richards, B. A. & Frankland, P. W. Forgetting at biologically realistic levels of neurogenesis in a large-scale hippocampal model. Behav. Brain Res. 376, 112180 (2019).

    PubMed  PubMed Central  Google Scholar 

  142. Chambers, R. A. & Conroy, S. K. Network modeling of adult neurogenesis: shifting rates of neuronal turnover optimally gears network learning according to novelty gradient. J. Cogn. Neurosci. 19, 1–12 (2007).

    PubMed  PubMed Central  Google Scholar 

  143. Jinde, S. et al. Hilar mossy cell degeneration causes transient dentate granule cell hyperexcitability and impaired pattern separation. Neuron 76, 1189–1200 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Scharfman, H. E. The enigmatic mossy cell of the dentate gyrus. Nat. Rev. Neurosci. 17, 562–575 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Botterill, J. J. et al. Bidirectional regulation of cognitive and anxiety-like behaviors by dentate gyrus mossy cells in male and female mice. J. Neurosci. 41, 2475–2495 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Nakashiba, T. et al. Young dentate granule cells mediate pattern separation, whereas old granule cells facilitate pattern completion. Cell 149, 188–201 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Clelland, C. et al. A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science 325, 210–213 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Sahay, A. et al. Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature 472, 466–470 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Masachs, N. et al. The temporal origin of dentate granule neurons dictates their role in spatial memory. Mol. Psychiatry 26, 7130–7140 (2021).

    PubMed  PubMed Central  Google Scholar 

  150. Saxe, M. D. et al. Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus. Proc. Natl Acad. Sci. USA 103, 17501–17506 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Morris, A. M., Curtis, B. J., Churchwell, J. C., Maasberg, D. W. & Kesner, R. P. Temporal associations for spatial events: the role of the dentate gyrus. Behav. Brain Res. 256, 250–256 (2013).

    PubMed  Google Scholar 

  152. Akers, K. G. et al. Hippocampal neurogenesis regulates forgetting during adulthood and infancy. Science 344, 598–602 (2014).

    CAS  PubMed  Google Scholar 

  153. Epp, J. R. et al. Neurogenesis-mediated forgetting minimizes proactive interference. Nat. Commun. 7, 10838 (2016).

    Google Scholar 

  154. Cuartero, M. I. et al. Abolition of aberrant neurogenesis ameliorates cognitive impairment after stroke in mice. J. Clin. Investig. 129, 1536–1550 (2019).

    PubMed  PubMed Central  Google Scholar 

  155. Ishikawa, R., Fukushima, H., Frankland, P. W. & Kida, S. Hippocampal neurogenesis enhancers promote forgetting of remote fear memory after hippocampal reactivation by retrieval. eLife 5, e17464 (2016).

    Google Scholar 

  156. Gao, A. et al. Elevation of hippocampal neurogenesis induces a temporally graded pattern of forgetting of contextual fear memories. J. Neurosci. 38, 3190–3198 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Ishikawa, R., Uchida, C., Kitaoka, S., Furuyashiki, T. & Kida, S. Improvement of PTSD-like behavior by the forgetting effect of hippocampal neurogenesis enhancer memantine in a social defeat stress paradigm. Mol. Brain 12, 68 (2019).

    PubMed  PubMed Central  Google Scholar 

  158. Scott, G. A. et al. Adult neurogenesis mediates forgetting of multiple types of memory in the rat. Mol. Brain 14, 97 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  159. Ryan, T. J. & Frankland, P. W. Forgetting as a form of adaptive engram cell plasticity. Nat. Rev. Neurosci. 23, 173–186 (2022).

    CAS  PubMed  Google Scholar 

  160. Fricke, R. A. & Prince, D. A. Electrophysiology of dentate gyrus granule cells. J. Neurophysiol. 51, 195–209 (1984).

    CAS  PubMed  Google Scholar 

  161. Scharfman, H. E. Blockade of excitation reveals inhibition of dentate spiny hilar neurons recorded in rat hippocampal slices. J. Neurophysiol. 68, 978–984 (1992).

    CAS  PubMed  Google Scholar 

  162. Staley, K. J. & Mody, I. Shunting of excitatory input to dentate gyrus granule cells by a depolarizing GABAA receptor-mediated postsynaptic conductance. J. Neurophysiol. 68, 197–212 (1992).

    CAS  PubMed  Google Scholar 

  163. Danielson, N. B. et al. In vivo imaging of dentate gyrus mossy cells in behaving mice. Neuron 93, 552–559 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  164. Botterill, J. J. et al. An excitatory and epileptogenic effect of dentate gyrus mossy cells in a mouse model of epilepsy. Cell Rep. 29, 2875–2889 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Nitz, D. & McNaughton, B. Differential modulation of CA1 and dentate gyrus interneurons during exploration of novel environments. J. Neurophysiol. 91, 863–872 (2004).

    PubMed  Google Scholar 

  166. Rangel, L. M., Chiba, A. A. & Quinn, L. K. Theta and beta oscillatory dynamics in the dentate gyrus reveal a shift in network processing state during cue encounters. Front. Syst. Neurosci. 9, 96 (2015).

    PubMed  PubMed Central  Google Scholar 

  167. Trimper, J. B., Galloway, C. R., Jones, A. C., Mandi, K. & Manns, J. R. Gamma oscillations in rat hippocampal subregions dentate gyrus, CA3, CA1, and subiculum underlie associative memory encoding. Cell Rep. 21, 2419–2432 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  168. Sasaki, T. et al. Dentate network activity is necessary for spatial working memory by supporting CA3 sharp-wave ripple generation and prospective firing of CA3 neurons. Nat. Neurosci. 21, 258–269 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  169. Sullivan, D. et al. Relationships between hippocampal sharp waves, ripples, and fast gamma oscillation: influence of dentate and entorhinal cortical activity. J. Neurosci. 31, 8605–8616 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  170. Luna, V. M. et al. Adult-born hippocampal neurons bidirectionally modulate entorhinal inputs into the dentate gyrus. Science 364, 578–583 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  171. Piatti, V. C., Ewell, L. A. & Leutgeb, J. K. Neurogenesis in the dentate gyrus: carrying the message or dictating the tone. Front. Neurosci. 7, 50 (2013).

    PubMed  PubMed Central  Google Scholar 

  172. Ikrar, T. et al. Adult neurogenesis modifies excitability of the dentate gyrus. Front. Neural Circ. 7, 204 (2013).

    CAS  Google Scholar 

  173. Trinchero, M. F., Giacomini, D. & Schinder, A. F. Dynamic interplay between GABAergic networks and developing neurons in the adult hippocampus. Curr. Opin. Neurobiol. 69, 124–130 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  174. Drew, L. J. et al. Activation of local inhibitory circuits in the dentate gyrus by adult‐born neurons. Hippocampus 26, 763–778 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  175. Lacefield, C. O., Itskov, V., Reardon, T., Hen, R. & Gordon, J. A. Effects of adult‐generated granule cells on coordinated network activity in the dentate gyrus. Hippocampus 22, 106–116 (2012).

    PubMed  Google Scholar 

  176. Berdugo-Vega, G. et al. Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life. Nat. Commun. 11, 135 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  177. McHugh, S. B. et al. Adult-born dentate granule cells promote hippocampal population sparsity. Nat. Neurosci. 25, 1481–1491 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  178. Aimone, J. B. et al. Regulation and function of adult neurogenesis: from genes to cognition. Physiol. Rev. 94, 991–1026 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  179. Scharfman, H. E., Goodman, J. H. & Sollas, A. L. Granule-like neurons at the hilar/CA3 border after status epilepticus and their synchrony with area CA3 pyramidal cells: functional implications of seizure-induced neurogenesis. J. Neurosci. 20, 6144–6158 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  180. Cho, K.-O. et al. Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline. Nat. Commun. 6, 6606 (2015).

    CAS  PubMed  Google Scholar 

  181. GoodSmith, D. et al. Flexible encoding of objects and space in single cells of the dentate gyrus. Curr. Biol. 32, 1088–1101 (2022).

    CAS  PubMed  PubMed Central  Google Scholar 

  182. Sahay, A., Wilson, D. A. & Hen, R. Pattern separation: a common function for new neurons in hippocampus and olfactory bulb. Neuron 70, 582–588 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  183. Si, B. & Treves, A. The role of competitive learning in the generation of DG fields from EC inputs. Cogn. Neurodyn. 3, 177–187 (2009).

    PubMed  PubMed Central  Google Scholar 

  184. Wang, C. et al. Egocentric coding of external items in the lateral entorhinal cortex. Science 362, 945–949 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  185. Morris, A. M., Weeden, C. S., Churchwell, J. C. & Kesner, R. P. The role of the dentate gyrus in the formation of contextual representations. Hippocampus 23, 162–168 (2013).

    PubMed  Google Scholar 

  186. Leutgeb, J. K., Leutgeb, S., Moser, M.-B. & Moser, E. I. Pattern separation in the dentate gyrus and CA3 of the hippocampus. Science 315, 961–966 (2007).

    CAS  PubMed  Google Scholar 

  187. Alme, C. B. et al. Place cells in the hippocampus: eleven maps for eleven rooms. Proc. Natl Acad. Sci. USA 111, 18428–18435 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  188. Deng, W., Mayford, M. & Gage, F. H. Selection of distinct populations of dentate granule cells in response to inputs as a mechanism for pattern separation in mice. eLife 2, e00312 (2013).

    Google Scholar 

  189. Kim, S. H. et al. Global remapping in granule cells and mossy cells of the mouse dentate gyrus. Cell Rep. 42, 112334 (2023).

    CAS  PubMed  Google Scholar 

  190. Hafting, T., Fyhn, M., Molden, S., Moser, M.-B. & Moser, E. I. Microstructure of a spatial map in the entorhinal cortex. Nature 436, 801–806 (2005).

    CAS  PubMed  Google Scholar 

  191. Keene, C. S. et al. Complementary functional organization of neuronal activity patterns in the perirhinal, lateral entorhinal, and medial entorhinal cortices. J. Neurosci. 36, 3660–3675 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  192. Wang, C., Chen, X. & Knierim, J. J. Egocentric and allocentric representations of space in the rodent brain. Curr. Opin. Neurobiol. 60, 12–20 (2020).

    CAS  PubMed  Google Scholar 

  193. Tsao, A. et al. Integrating time from experience in the lateral entorhinal cortex. Nature 561, 57–62 (2018).

    CAS  PubMed  Google Scholar 

  194. Dvorak, D., Chung, A., Park, E. H. & Fenton, A. A. Dentate spikes and external control of hippocampal function. Cell Rep. 36, 109497 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  195. Fernández-Ruiz, A. et al. Gamma rhythm communication between entorhinal cortex and dentate gyrus neuronal assemblies. Science 372, eabf3119 (2021).

    PubMed  PubMed Central  Google Scholar 

  196. Jung, M. W., Wiener, S. I. & McNaughton, B. L. Comparison of spatial firing characteristics of units in dorsal and ventral hippocampus of the rat. J. Neurosci. 14, 7347–7356 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  197. Chawla, M. et al. Sparse, environmentally selective expression of Arc RNA in the upper blade of the rodent fascia dentata by brief spatial experience. Hippocampus 15, 579–586 (2005).

    CAS  PubMed  Google Scholar 

  198. Lu, L., Igarashi, K. M., Witter, M. P., Moser, E. I. & Moser, M.-B. Topography of place maps along the CA3-to-CA2 axis of the hippocampus. Neuron 87, 1078–1092 (2015).

    CAS  PubMed  Google Scholar 

  199. Van Strien, N., Cappaert, N. & Witter, M. The anatomy of memory: an interactive overview of the parahippocampal–hippocampal network. Nat. Rev. Neurosci. 10, 272–282 (2009).

    PubMed  Google Scholar 

  200. Royer, S., Sirota, A., Patel, J. & Buzsáki, G. Distinct representations and theta dynamics in dorsal and ventral hippocampus. J. Neurosci. 30, 1777–1787 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  201. Jung, M. W., Wiener, S. I. & McNaughton, B. L. Comparison of spatial firing characteristics of units in dorsal and ventral hippocampus of the rat. J. Neurosci. 14, 7347–7356 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  202. Kjelstrup, K. B. et al. Finite scale of spatial representation in the hippocampus. Science 321, 140–143 (2008).

    CAS  PubMed  Google Scholar 

  203. Keinath, A. T. et al. Precise spatial coding is preserved along the longitudinal hippocampal axis. Hippocampus 24, 1533–1548 (2014).

    PubMed  PubMed Central  Google Scholar 

  204. Jinno, S. & Kosaka, T. Stereological estimation of numerical densities of glutamatergic principal neurons in the mouse hippocampus. Hippocampus 20, 829–840 (2010).

    PubMed  Google Scholar 

  205. Tanaka, K. F., Samuels, B. A. & Hen, R. Serotonin receptor expression along the dorsal–ventral axis of mouse hippocampus. Philos. Trans. R. Soc. B: Biol. Sci. 367, 2395–2401 (2012).

    CAS  Google Scholar 

  206. Christensen, T., Bisgaard, C., Nielsen, H. B. & Wiborg, O. Transcriptome differentiation along the dorso–ventral axis in laser-captured microdissected rat hippocampal granular cell layer. Neuroscience 170, 731–741 (2010).

    CAS  PubMed  Google Scholar 

  207. Fanselow, M. S. & Dong, H.-W. Are the dorsal and ventral hippocampus functionally distinct structures? Neuron 65, 7–19 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  208. Witter, M. P. & Amaral, D. G. in The Rat Nervous System 635–704 (Elsevier, 2004).

  209. Paxinos, G. The Rat Nervous System (Gulf Professional Publishing, 2004).

  210. Amaral, D. G. & Witter, M. P. The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience 31, 571–591 (1989).

    CAS  PubMed  Google Scholar 

  211. Scharfman, H. E., Sollas, A. L., Smith, K. L., Jackson, M. B. & Goodman, J. H. Structural and functional asymmetry in the normal and epileptic rat dentate gyrus. J. Comp. Neurol. 454, 424–439 (2002).

    PubMed  PubMed Central  Google Scholar 

  212. Witter, M. P. Intrinsic and extrinsic wiring of CA3: indications for connectional heterogeneity. Learn. Mem. 14, 705–713 (2007).

    PubMed  Google Scholar 

  213. Lee, H., Wang, C., Deshmukh, S. S. & Knierim, J. J. Neural population evidence of functional heterogeneity along the CA3 transverse axis: pattern completion versus pattern separation. Neuron 87, 1093–1105 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  214. Scharfman, H. E. Spiny neurons of area CA3c in rat hippocampal slices have similar electrophysiological characteristics and synaptic responses despite morphological variation. Hippocampus 3, 9–28 (1993).

    CAS  PubMed  Google Scholar 

  215. Claiborne, B. J., Amaral, D. G. & Cowan, W. M. A light and electron microscopic analysis of the mossy fibers of the rat dentate gyrus. J. Comp. Neurol. 246, 435–458 (1986).

    CAS  PubMed  Google Scholar 

  216. Ishizuka, N., Weber, J. & Amaral, D. G. Organization of intrahippocampal projections originating from CA3 pyramidal cells in the rat. J. Comp. Neurol. 295, 580–623 (1990).

    CAS  PubMed  Google Scholar 

  217. Li, X., Somogyi, P., Ylinen, A. & Buzsáki, G. The hippocampal CA3 network: an in vivo intracellular labeling study. J. Comp. Neurol. 339, 181–208 (1994).

    CAS  PubMed  Google Scholar 

  218. Lee, I., Yoganarasimha, D., Rao, G. & Knierim, J. J. Comparison of population coherence of place cells in hippocampal subfields CA1 and CA3. Nature 430, 456–459 (2004).

    CAS  PubMed  Google Scholar 

  219. Tosches, M. A. et al. Evolution of pallium, hippocampus, and cortical cell types revealed by single-cell transcriptomics in reptiles. Science 360, 881–888 (2018).

    CAS  PubMed  Google Scholar 

  220. Bingman, V. P. & Muzio, R. N. Reflections on the structural–functional evolution of the hippocampus: what is the big deal about a dentate gyrus. Brain Behav. Evol. 90, 53–61 (2017).

    PubMed  Google Scholar 

  221. Treves, A., Tashiro, A., Witter, M. P. & Moser, E. I. What is the mammalian dentate gyrus good for? Neuroscience 154, 1155–1172 (2008).

    CAS  PubMed  Google Scholar 

  222. Amrein, I., Slomianka, L. & Lipp, H. Granule cell number, cell death and cell proliferation in the dentate gyrus of wild‐living rodents. Eur. J. Neurosci. 20, 3342–3350 (2004).

    PubMed  Google Scholar 

  223. Amrein, I. Adult hippocampal neurogenesis in natural populations of mammals. Cold Spring Harb. Perspect. Biol. 7, a021295 (2015).

    PubMed  PubMed Central  Google Scholar 

  224. Fiedler, J., De Leonibus, E. & Treves, A. Has the hippocampus really forgotten about space? Curr. Opin. Neurobiol. 71, 164–169 (2021).

    CAS  PubMed  Google Scholar 

  225. Augusto-Oliveira, M., Arrifano, G. P., Malva, J. O. & Crespo-Lopez, M. E. Adult hippocampal neurogenesis in different taxonomic groups: possible functional similarities and striking controversies. Cells 8, 125 (2019).

    PubMed  PubMed Central  Google Scholar 

  226. Rodrı́guez, F. et al. Conservation of spatial memory function in the pallial forebrain of reptiles and ray-finned fishes. J. Neurosci. 22, 2894–2903 (2002).

    PubMed  PubMed Central  Google Scholar 

  227. Allegra, M., Posani, L., Gómez-Ocádiz, R. & Schmidt-Hieber, C. Differential relation between neuronal and behavioral discrimination during hippocampal memory encoding. Neuron 108, 1103–1112 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  228. Stefanini, F. et al. A distributed neural code in the dentate gyrus and in CA1. Neuron 107, 703–716 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  229. Lin, B., Chen, T. & Schild, D. Cell type‐specific relationships between spiking and [Ca2+] i in neurons of the Xenopus tadpole olfactory bulb. J. Physiol. 582, 163–175 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  230. Kropff, E., Yang, S. M. & Schinder, A. F. Dynamic role of adult-born dentate granule cells in memory processing. Curr. Opin. Neurobiol. 35, 21–26 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  231. Snyder, J. S. Recalibrating the relevance of adult neurogenesis. Trends Neurosci. 42, 164–178 (2019).

    CAS  PubMed  Google Scholar 

  232. Danielson, N. B. et al. Distinct contribution of adult-born hippocampal granule cells to context encoding. Neuron 90, 101–112 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  233. Alvarez, D. D. et al. A disynaptic feedback network activated by experience promotes the integration of new granule cells. Science 354, 459–465 (2016).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was partially supported by the NSF DMS-1042134, NIH R03MH120406, NIH R01 NS039456, NRF 2021R1A4A2001803, NRF 2019R1A2C2088799, NRF 2022M3E5E8017723, the NIH Institute of Neural Computation/Biology T32 MH020002 and the Kavli Institute for Brain and Mind. The authors gratefully thank D. Nitz, L.K. Quinn, J.W. Rueckemann, T. Johnson, P. Riviere and C. Heyman for insightful discussions and editorial assistance.

Author information

Authors and Affiliations

Authors

Contributions

The authors contributed to all aspects of the article.

Corresponding author

Correspondence to Lara M. Rangel.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Neuroscience thanks A. Schinder and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Borzello, M., Ramirez, S., Treves, A. et al. Assessments of dentate gyrus function: discoveries and debates. Nat. Rev. Neurosci. 24, 502–517 (2023). https://doi.org/10.1038/s41583-023-00710-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41583-023-00710-z

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing