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.

The anterior thalamic nuclei: core components of a tripartite episodic memory system

Abstract

Standard models of episodic memory focus on hippocampal–parahippocampal interactions, with the neocortex supplying sensory information and providing a final repository of mnemonic representations. However, recent advances have shown that other regions make distinct and equally critical contributions to memory. In particular, there is growing evidence that the anterior thalamic nuclei have a number of key cognitive functions that support episodic memory. In this article, we describe these findings and argue for a core, tripartite memory system, comprising a ‘temporal lobe’ stream (centred on the hippocampus) and a ‘medial diencephalic’ stream (centred on the anterior thalamic nuclei) that together act on shared cortical areas. We demonstrate how these distributed brain regions form complementary and necessary partnerships in episodic memory formation.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Fig. 1: Location of the anterior thalamic nuclei.
Fig. 2: Principal connections of the anterior thalamic nuclei.
Fig. 3: Proposed anterior thalamic participation in cognition.
Fig. 4: A core, tripartite episodic memory system.

References

  1. Eichenbaum, H. A cortical–hippocampal system for declarative memory. Nat. Rev. Neurosci. 1, 41–50 (2000).

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  3. Squire, L. R. Memory and brain systems: 1969–2009. J. Neurosci. 29, 12711–12716 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Bellmund, J. L., Gärdenfors, P., Moser, E. I. & Doeller, C. F. Navigating cognition: spatial codes for human thinking. Science 362, 6415 (2018).

    Article  CAS  Google Scholar 

  5. Ekstrom, A. D. & Ranganath, C. Space, time, and episodic memory: the hippocampus is all over the cognitive map. Hippocampus 28, 680–687 (2018).

    Article  PubMed  Google Scholar 

  6. Gudden, H. Klinische und anatommische beitrage zur kenntnis der multiplen alkoholneuritis nebst bemerzungen uber die regenerationsvorgange im peripheren nervensystem. Arch. Psychiat. 28, 643–741 (1896).

    Article  Google Scholar 

  7. Gamper, E. Zur Frage der Polioencephalitis hæmorrhagica der chronischen Alkoholiker: Anatomische Befund beim alkoholischen Korsakow und ihre Beziehungen zum klinischen Bild. Dtsch. Ztschr. Nervenh 102, 122 (1928).

    Article  Google Scholar 

  8. Kopelman, M. D. What does a comparison of the alcoholic Korsakoff syndrome and thalamic infarction tell us about thalamic amnesia? Neurosci. Biobehav. Rev. 54, 46–56 (2015).

    Article  PubMed  Google Scholar 

  9. Gabriel, M. in Neurobiology of Cingulate Cortex and Limbic Thalamus (eds. Vogt, B. A. & Gabriel, M.) 478–523 (Birkhäuser, 1993).

  10. Wright, N. F., Vann, S. D., Aggleton, J. P. & Nelson, A. J. A critical role for the anterior thalamus in directing attention to task-relevant stimuli. J. Neurosci. 35, 5480–5488 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Aggleton, J. P. & Nelson, A. J. Why do lesions in the rodent anterior thalamic nuclei cause such severe spatial deficits? Neurosc. Biobehav. Rev. 54, 131–144 (2015).

    Article  Google Scholar 

  12. Aggleton, J. P. et al. Hippocampal–anterior thalamic pathways for memory: uncovering a network of direct and indirect actions. Eur. J. Neurosci. 31, 2292–2307 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Aggleton, J. P. & Pearce, J. M. Neural systems underlying episodic memory: insights from animal research. Philos. Trans. R. Soc. Lond. B Biol. Sci. 356, 1467–1482 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bird, C. M. & Burgess, N. The hippocampus and memory: insights from spatial processing. Nat. Rev. Neurosci. 9, 182–194 (2008).

    Article  CAS  PubMed  Google Scholar 

  15. Barry, D. N. & Maguire, E. A. Remote memory and the hippocampus: a constructive critique. Trends Cogn. Sci. 23, 128–142 (2019).

    Article  PubMed  Google Scholar 

  16. Yonelinas, A. P., Ranganath, C., Ekstrom, A. D. & Wiltgen, B. J. A contextual binding theory of episodic memory: systems consolidation reconsidered. Nat. Rev. Neurosci. 20, 364–375 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Yamawaki, N. et al. Long-range inhibitory intersection of a retrosplenial thalamocortical circuit by apical tuft-targeting CA1 neurons. Nat. Neurosci. 22, 618–626 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Taube, J. S. The head direction signal: origins and sensory-motor integration. Annu. Rev. Neurosci. 30, 181–207 (2007).

    Article  CAS  PubMed  Google Scholar 

  19. Goodridge, J. P. & Taube, J. S. Interaction between the postsubiculum and anterior thalamus in the generation of head direction cell activity. J. Neurosci. 17, 9315–9330 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Winter, S. S., Clark, B. J. & Taube, J. S. Disruption of the head direction cell network impairs the parahippocampal grid cell signal. Science 347, 870–874 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Nelson, A. J., Kinnavane, L., Amin, E., O’Mara, S. M. & Aggleton, J. P. Deconstructing the direct reciprocal hippocampal-anterior thalamic pathways for spatial learning. J. Neurosci. 40, 6978–6990 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Bourbon-Teles, J. et al. Thalamic control of human attention driven by memory and learning. Curr. Biol. 24, 993–999 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Lawson, R. On the symptomatology of alcoholic brain disorders. Brain 1, 182–194 (1878).

    Article  Google Scholar 

  24. Korsakoff, S. S. Ob alkogol’nom paraliche (Of alcoholic paralysis: disturbance of psychic activity and its relation to the disturbance of the psychic sphere in multiple neuritis of nonalcoholic origin). Vestnick. Klin. Psychiat. Neurol. 4, 1–102 (1887).

    Google Scholar 

  25. Harding, A., Halliday, G., Caine, D. & Kril, J. Degeneration of anterior thalamic nuclei differentiates alcoholics with amnesia. Brain 123, 141–154 (2000).

    Article  PubMed  Google Scholar 

  26. Guillery, R. W. A quantitative study of the mamillary bodies and their connexions. J. Anat. 89, 19–32 (1955).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Takeuchi, Y., Allen, G. V. & Hopkins, D. A. Transnuclear transport and axon collateral projections of the mamillary nuclei in the rat. Brain Res. Bull. 14, 453–468 (1985).

    Article  CAS  PubMed  Google Scholar 

  28. von Bekhterev, M. Demonstration eines Gehirns mit Zerstö rung der vorderen und inneren Theile der Hirnrinde beider Schlä fenlappen. Neurologisches Zeitblatt 19, 990–991 (1900).

    Google Scholar 

  29. Clark, R. E. & Squire, L. R. An animal model of recognition memory and medial temporal lobe amnesia: history and current issues. Neuropsychologia 48, 2234–2244 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Scoville, W. B. & Milner, B. Loss of recent memory after bilateral hippocampal lesions. J. Neurol. Neurosurg. Psychiat. 20, 11–21 (1957).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Zola-Morgan, S., Squire, L. R. & Amaral, D. G. Human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field CA1 of the hippocampus. J. Neurosci. 6, 2950–2967 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Rempel-Clower, N. L., Zola, S. M., Squire, L. R. & Amaral, D. G. Three cases of enduring memory impairment after bilateral damage limited to the hippocampal formation. J. Neurosci. 16, 5233–5255 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Spiers, H. J., Maguire, E. A. & Burgess, N. Hippocampal amnesia. Neurocase 7, 357–382 (2001).

    Article  CAS  PubMed  Google Scholar 

  34. Papez, J. W. A proposed mechanism of emotion. Arch. Neurol. Psychiat. 38, 725–743 (1937).

    Article  Google Scholar 

  35. Bastin, C. et al. An integrative memory model of recollection and familiarity to understand memory deficits. Behav. Brain Sci. 42, e281 (2019).

    Article  PubMed  Google Scholar 

  36. Delay, J. & Brion, S. Le Syndrome de Korsakoff (Masson, 1969).

  37. Aggleton, J. P. & Brown, M. W. Episodic memory, amnesia and the hippocampal-anterior thalamic axis. Behav. Brain Sci. 22, 425–444 (1999).

    Article  CAS  PubMed  Google Scholar 

  38. O’Keefe, J. & Dostrovsky, J. The hippocampus as a spatial map: preliminary evidence from unit activity in the freely-moving rat. Brain Res. 34, 171–174 (1971).

    Article  PubMed  Google Scholar 

  39. Bliss, T. V. & Lømo, T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J. Physiol. 232, 331–356 (1973).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Morris, R. G., Garrud, P., Rawlins, J. A. & O’Keefe, J. Place navigation impaired in rats with hippocampal lesions. Nature 297, 681–683 (1982).

    Article  CAS  PubMed  Google Scholar 

  41. Eichenbaum, H. Prefrontal–hippocampal interactions in episodic memory. Nat. Rev. Neurosci. 18, 547–558 (2017).

    Article  CAS  PubMed  Google Scholar 

  42. Korotkova, T. et al. Reconciling the different faces of hippocampal theta: the role of theta oscillations in cognitive, emotional and innate behaviors. Neurosci. Biobehav. Rev. 85, 65–80 (2018).

    Article  PubMed  Google Scholar 

  43. Watrous, A. J. et al. A comparative study of human and rat hippocampal low-frequency oscillations during spatial navigation. Hippocampus 23, 656–661 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Addante, R. J., Watrous, A. J., Yonelinas, A. P., Ekstrom, A. D. & Ranganath, C. Prestimulus theta activity predicts correct source memory retrieval. Proc. Natl Acad. Sci. USA 108, 10702–10707 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Horner, A. J. & Doeller, C. F. Plasticity of hippocampal memories in humans. Curr. Opin. Neurobiol. 43, 102–109 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kota, S., Rugg, M. D. & Lega, B. C. Hippocampal theta oscillations support successful associative memory formation. J. Neurosci. 40, 9507–9518 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Zeidman, P. & Maguire, E. A. Anterior hippocampus: the anatomy of perception, imagination and episodic memory. Nat. Rev. Neurosci. 17, 173–182 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Nadel, L., Samsonovich, A., Ryan, L. & Moscovitch, M. Multiple trace theory of human memory: computational, neuroimaging, and neuropsychological results. Hippocampus 10, 352–368 (2000).

    Article  CAS  PubMed  Google Scholar 

  49. Squire, L. R., Genzel, L., Wixted, J. T. & Morris, R. G. Memory consolidation. Cold Spring Harb. Persp. Biol. 7, a021766 (2015).

    Article  Google Scholar 

  50. Ritchey, M., Libby, L. A. & Ranganath, C. Cortico-hippocampal systems involved in memory and cognition: the PMAT framework. Progr. Brain Res. 219, 45–64 (2015).

    Article  Google Scholar 

  51. Fama, R. & Sullivan, E. V. Thalamic structures and associated cognitive functions: relations with age and aging. Neurosci. Biobehav. Rev. 54, 29–37 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Alderson, T. et al. Disrupted thalamus white matter anatomy and posterior default mode network effective connectivity in amnestic mild cognitive impairment. Front. Aging Neurosci. 9, 370 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Aggleton, J. P., Pralus, A., Nelson, A. J. & Hornberger, M. Thalamic pathology and memory loss in early Alzheimer’s disease: moving the focus from the medial temporal lobe to Papez circuit. Brain 139, 1877–1890 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Braak, H. & Braak, E. Alzheimer’s disease affects limbic nuclei of the thalamus. Acta Neuropath 81, 261–268 (1991).

    Article  CAS  PubMed  Google Scholar 

  55. Forno, G., Lladó, A. & Hornberger, M. Going round in circles — the Papez circuit in Alzheimer’s disease. Eur. J. Neurosci. 54, 7668–7687 (2021).

    Article  PubMed  Google Scholar 

  56. Elvsåshagen, T. et al. The genetic architecture of the human thalamus and its overlap with ten common brain disorders. Nat. Commun. 12, 2909 (2021).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Siniatchkin, M., Coropceanu, D., Moeller, F., Boor, R. & Stephani, U. EEG-fMRI reveals activation of brainstem and thalamus in patients with Lennox-Gastaut syndrome. Epilepsia 52, 766–774 (2011).

    Article  PubMed  Google Scholar 

  58. Perry, J. C., Pakkenberg, B. & Vann, S. D. Striking reduction in neurons and glial cells in anterior thalamic nuclei of older patients with Down syndrome. Neurobiol. Aging 75, 54–61 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. O’Mara, S. M. & Aggleton, J. P. Space and memory (far) beyond the hippocampus: many subcortical structures also support cognitive mapping and mnemonic processing. Front. Neur. Circ. 13, 52 (2019).

    Article  Google Scholar 

  60. Wright, N. F., Vann, S. D., Erichsen, J. T., O’Mara, S. M. & Aggleton, J. P. Segregation of parallel inputs to the anteromedial and anteroventral thalamic nuclei of the rat. J. Comp. Neurol. 521, 2966–2986 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Christiansen, K. et al. Complementary subicular pathways to the anterior thalamic nuclei and mammillary bodies in the rat and macaque monkey brain. Eur. J. Neurosci. 43, 1044–1061 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Mathiasen, M. L., Nelson, A. J., Amin, E., O’Mara, S. M. & Aggleton, J. P. A direct comparison of afferents to the rat anterior thalamic nuclei and nucleus reuniens: overlapping but different. eNeuro 8, https://doi.org/10.1523/ENEURO.0103-20.2021 (2021).

  63. Shibata, H. Direct projections from the anterior thalamic nuclei to the retrohippocampal region in the rat. J. Comp. Neurol. 337, 431–445 (1993).

    Article  CAS  PubMed  Google Scholar 

  64. Bubb, E. J., Kinnavane, L. & Aggleton, J. P. Hippocampal–diencephalic–cingulate networks for memory and emotion: an anatomical guide. Brain Neurosci. Adv. 1, 2398212817723443 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  65. Cenquizca, L. A. & Swanson, L. W. Analysis of direct hippocampal cortical field CA1 axonal projections to diencephalon in the rat. J. Comp. Neurol. 497, 101–114 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Vetere, G. et al. An inhibitory hippocampal–thalamic pathway modulates remote memory retrieval. Nat. Neurosci. 24, 685–693 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Ferguson, M. A. et al. A human memory circuit derived from brain lesions causing amnesia. Nat. Commun. 10, 3497 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Wolff, M. & Vann, S. D. The cognitive thalamus as a gateway to mental representations. J. Neurosci. 39, 3–14 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Mitchell, A. S. & Chakraborty, S. What does the mediodorsal thalamus do? Front. Syst. Neurosci. 7, 37 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  70. Perry, B. A., Lomi, E. & Mitchell, A. S. Thalamocortical interactions in cognition and disease: the mediodorsal and anterior thalamic nuclei. Neurosci. Biobehav. Rev. 130, 162–177 (2021).

    Article  PubMed  Google Scholar 

  71. Mathiasen, M. L., O’Mara, S. M. & Aggleton, J. P. The anterior thalamic nuclei and nucleus reuniens: so similar but so different. Neurosci. Biobehav. Rev. 119, 268–280 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Moreau, P. H. et al. Lesions of the anterior thalamic nuclei and intralaminar thalamic nuclei: place and visual discrimination learning in the water maze. Brain Struct. Funct. 218, 657–667 (2013).

    Article  PubMed  Google Scholar 

  73. Warburton, E. C. & Aggleton, J. P. Differential deficits in the Morris water maze following cytotoxic lesions of the anterior thalamus and fornix transection. Behav. Brain Res. 98, 27–38 (1998).

    Article  Google Scholar 

  74. Dolleman-van der Weel, M. J., Morris, R. G. & Witter, M. P. Neurotoxic lesions of the thalamic reuniens or mediodorsal nucleus in rats affect non-mnemonic aspects of watermaze learning. Brain Struct. Funct. 213, 329–342 (2009).

    Article  PubMed  Google Scholar 

  75. Loureiro, M. et al. The ventral midline thalamus (reuniens and rhomboid nuclei) contributes to the persistence of spatial memory in rats. J. Neurosci. 32, 9947–9959 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. McKenna, J. T. & Vertes, R. P. Afferent projections to nucleus reuniens of the thalamus. J. Comp. Neurol. 480, 115–142 (2004).

    Article  PubMed  Google Scholar 

  77. Mathiasen, M. L. et al. Separate cortical and hippocampal cell populations target the rat nucleus reuniens and mammillary bodies. Eur. J. Neurosci. 49, 1649–1672 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  78. Prasad, J. A. & Chudasama, Y. Viral tracing identifies parallel disynaptic pathways to the hippocampus. J. Neurosci. 33, 8494–8503 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Griffin, A. L. The nucleus reuniens orchestrates prefrontal-hippocampal synchrony during spatial working memory. Neurosci. Biobehav. Rev. 128, 415–420 (2021).

    Article  PubMed  Google Scholar 

  80. Cassel, J. C. et al. The reuniens and rhomboid nuclei of the thalamus: a crossroads for cognition-relevant information processing? Neurosci. Biobehav. Rev. 126, 338–360 (2021).

    Article  CAS  PubMed  Google Scholar 

  81. Mitchell, A. S. The mediodorsal thalamus as a higher order thalamic relay nucleus important for learning and decision-making. Neurosci. Biobehav. Rev. 54, 76–88 (2015).

    Article  PubMed  Google Scholar 

  82. Hunt, P. R. & Aggleton, J. P. Medial dorsal thalamic lesions and working memory in the rat. Behav. Neural Biol. 55, 227–246 (1991).

    Article  CAS  PubMed  Google Scholar 

  83. Aggleton, J. P., Dumont, J. R. & Warburton, E. C. Unraveling the contributions of the diencephalon to recognition memory: a review. Learn. Mem. 18, 384–400 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Segobin, S. et al. Dissociating thalamic alterations in alcohol use disorder defines specificity of Korsakoff’s syndrome. Brain 142, 1458–1470 (2019).

    Article  PubMed  Google Scholar 

  85. Van der Werf, Y. D. et al. Deficits of memory, executive functioning and attention following infarction in the thalamus; a study of 22 cases with localised lesions. Neuropsychologia 41, 1330–1344 (2003).

    Article  PubMed  Google Scholar 

  86. Carlesimo, G. A., Lombardi, M. G. & Caltagirone, C. Vascular thalamic amnesia: a reappraisal. Neuropsychologia 49, 777–789 (2011).

    Article  PubMed  Google Scholar 

  87. Mair, R. G., Burk, J. A. & Porter, M. C. Impairment of radial maze delayed nonmatching after lesions of anterior thalamus and parahippocampal cortex. Behav. Neurosci. 117, 596–605 (2003).

    Article  PubMed  Google Scholar 

  88. Mitchell, A. S. & Dalrymple-Alford, J. C. Lateral and anterior thalamic lesions impair independent memory systems. Learn. Mem. 13, 388–396 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Clark, B. J. & Harvey, R. E. Do the anterior and lateral thalamic nuclei make distinct contributions to spatial representation and memory? Neurobiol. Learn. Mem. 133, 69–78 (2016).

    Article  PubMed  Google Scholar 

  90. Aggleton, J. P., Vann, S. D., Oswald, C. J. & Good, M. Identifying cortical inputs to the rat hippocampus that subserve allocentric spatial processes: a simple problem with a complex answer. Hippocampus 10, 466–474 (2000).

    Article  CAS  PubMed  Google Scholar 

  91. Moran, J. P. & Dalrymple-Alford, J. C. Perirhinal cortex and anterior thalamic lesions: comparative effects on learning and memory. Behav. Neurosci. 117, 1326–1341 (2003).

    Article  PubMed  Google Scholar 

  92. Cassel, J. C., Duconseille, E., Jeltsch, H. & Will, B. The fimbria-fornix/cingular bundle pathways: a review of neurochemical and behavioural approaches using lesions and transplantation techniques. Progr. Neurobiol. 51, 663–716 (1997).

    Article  CAS  Google Scholar 

  93. Aggleton, J. P. & Brown, M. W. in Neuropsychology of Memory (eds. Squire, L. R. & Schacter, D. L.) 377–394 (Guilford, 2002).

  94. Aggleton, J. P., Neave, N., Nagle, S. & Hunt, P. R. A comparison of the effects of anterior thalamic, mamillary body and fornix lesions on reinforced spatial alternation. Behav. Brain Res. 68, 91–101 (1995).

    Article  CAS  PubMed  Google Scholar 

  95. Parker, A. & Gaffan, D. The effect of anterior thalamic and cingulate cortex lesions on object-in-place memory in monkeys. Neuropsychologia 35, 1093–1102 (1997).

    Article  CAS  PubMed  Google Scholar 

  96. Gaffan, D. Scene-specific memory for objects: a model of episodic memory impairment in monkeys with fornix transection. J. Cogn. Neurosci. 6, 305–320 (1994).

    Article  CAS  PubMed  Google Scholar 

  97. Sutherland, R. J. & Rodriguez, A. J. The role of the fornix/fimbria and some related subcortical structures in place learning and memory. Behav. Brain Res. 32, 265–277 (1989).

    Article  CAS  PubMed  Google Scholar 

  98. Aggleton, J. P., Keith, A. B. & Sahgal, A. Both fornix and anterior thalamic, but not mammillary, lesions disrupt delayed non-matching-to-position memory in rats. Behav. Brain Res. 44, 151–161 (1991).

    Article  CAS  PubMed  Google Scholar 

  99. Dumont, J. R., Wright, N. F., Pearce, J. M. & Aggleton, J. P. The impact of anterior thalamic lesions on active and passive spatial learning in stimulus controlled environments: geometric cues and pattern arrangement. Behav. Neurosci. 128, 161–177 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  100. Pearce, J. M., Good, M. A., Jones, P. M. & McGregor, A. Transfer of spatial behavior between different environments: implications for theories of spatial learning and for the role of the hippocampus in spatial learning. J. Exp. Psych. Anim. Behav. Proc. 30, 135 (2004).

    Article  Google Scholar 

  101. Aggleton, J. P., Keith, A. B., Rawlins, J. N. P., Hunt, P. R. & Sahgal, A. Removal of the hippocampus and transection of the fornix produce comparable deficits on delayed non-matching to position by rats. Behav. Brain Res. 52, 61–71 (1992).

    Article  CAS  PubMed  Google Scholar 

  102. Song, D. et al. Extraction and restoration of hippocampal spatial memories with non-linear dynamical modeling. Front. Syst. Neurosci. 8, 97 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Morris, R. G. M., Schenk, F., Tweedie, F. & Jarrard, L. E. Ibotenate lesions of hippocampus and/or subiculum: dissociating components of allocentric spatial learning. Eur. J. Neurosci. 2, 1016–1028 (1990).

    Article  PubMed  Google Scholar 

  104. Jarrard, L. E. What does the hippocampus really do? Behav. Brain Res. 71, 1–10 (1995).

    Article  CAS  PubMed  Google Scholar 

  105. Taube, J. S. Head direction cells recorded in the anterior thalamic nuclei of freely moving rats. J. Neurosci. 15, 70–86 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Calton, J. L. et al. Hippocampal place cell instability after lesions of the head direction cell network. J. Neurosci. 23, 9719–9731 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Moser, E. I. et al. Grid cells and cortical representation. Nat. Rev. Neurosci. 15, 466–481 (2014).

    Article  CAS  PubMed  Google Scholar 

  108. Golob, E. J. & Taube, J. S. Head direction cells and episodic spatial information in rats without a hippocampus. Proc. Natl Acad. Sci. USA 94, 7645–7650 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Safari, V. et al. Individual subnuclei of the rat anterior thalamic nuclei differently affect spatial memory and passive avoidance tasks. Neuroscience 444, 19–32 (2020).

    Article  CAS  PubMed  Google Scholar 

  110. Vann, S. D. Transient spatial deficit associated with bilateral lesions of the lateral mammillary nuclei. Eur. J. Neurosci. 21, 820–824 (2005).

    Article  PubMed  Google Scholar 

  111. Dillingham, C. M. & Vann, S. D. Why isn’t the head direction system necessary for direction? lessons from the lateral mammillary nuclei. Front. Neur. Circ. 13, 60 (2019).

    Article  Google Scholar 

  112. van Groen, T., Kadish, I. & Wyss, J. M. Role of the anterodorsal and anteroventral nuclei of the thalamus in spatial memory in the rat. Behav. Brain Res. 132, 19–28 (2002).

    Article  PubMed  Google Scholar 

  113. Moser, E. I., Moser, M. B. & McNaughton, B. L. Spatial representation in the hippocampal formation: a history. Nat. Neurosci. 20, 1448–1464 (2017).

    Article  CAS  PubMed  Google Scholar 

  114. Matulewicz, P. et al. Proximal perimeter encoding in the rat rostral thalamus. Sci. Rep. 9, 2568 (2019).

    Article  CAS  Google Scholar 

  115. Jankowski, M. M. et al. Evidence for spatially-responsive neurons in the rostral thalamus. Front. Behav. Neurosci. 9, 256 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  116. Tsanov, M. et al. Theta-modulated head direction cells in the rat anterior thalamus. J. Neurosci. 31, 9489–9502 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Horikawa, K., Kinjo, N., Stanley, L. C. & Powell, E. W. Topographic organization and collateralization of the projections of the anterior and laterodorsal thalamic nuclei to cingulate areas 24 and 29 in the rat. Neurosci. Res. 6, 31–44 (1988).

    Article  CAS  PubMed  Google Scholar 

  118. Gibson, W. S. et al. Anterior thalamic deep brain stimulation: functional activation patterns in a large animal model. Brain Stim 9, 770–773 (2016).

    Article  Google Scholar 

  119. Horner, A. J., Bisby, J. A., Wang, A., Bogus, K. & Burgess, N. The role of spatial boundaries in shaping long-term event representations. Cognition 154, 151–164 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  120. Tsanov, M. et al. Differential regulation of synaptic plasticity of the hippocampal and the hypothalamic inputs to the anterior thalamus. Hippocampus 21, 1–8 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  121. Bauch, E. M. et al. Theta oscillations underlie retrieval success effects in the nucleus accumbens and anterior thalamus: evidence from human intracranial recordings. Neurobiol. Learn. Mem. 155, 104–112 (2018).

    Article  PubMed  Google Scholar 

  122. Sweeney-Reed, C. M. et al. Corticothalamic phase synchrony and cross-frequency coupling predict human memory formation. Elife 3, e05352 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  123. Sweeney-Reed, C. M. et al. Thalamic theta phase alignment predicts human memory formation and anterior thalamic cross-frequency coupling. Elife 4, e07578 (2015).

    Article  PubMed Central  Google Scholar 

  124. Sweeney-Reed, C. M. et al. The role of the anterior nuclei of the thalamus in human memory processing. Neurosci. Biobehav. Rev. 126, 146–158 (2021).

    Article  PubMed  Google Scholar 

  125. Li, A. W. & King, J. Spatial memory and navigation in ageing: a systematic review of MRI and fMRI studies in healthy participants. Neurosci. Biobehav. Rev. 103, 33–49 (2019).

    Article  PubMed  Google Scholar 

  126. Fritch, H. A. et al. The anterior hippocampus is associated with spatial memory encoding. Brain Res. 1732, 146696 (2020).

    Article  CAS  PubMed  Google Scholar 

  127. Petersen, R. C. et al. Memory and MRI-based hippocampal volumes in aging and AD. Neurology 54, 581–581 (2000).

    Article  CAS  PubMed  Google Scholar 

  128. Rugg, M. D. et al. Item memory, context memory and the hippocampus: fMRI evidence. Neuropsychologia 50, 3070–3079 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  129. Hou, M., De Chastelaine, M., Jayakumar, M., Donley, B. E. & Rugg, M. D. Recollection-related hippocampal fMRI effects predict longitudinal memory change in healthy older adults. Neuropsychologia 146, 107537 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  130. Geier, K. T., Buchsbaum, B. R., Parimoo, S. & Olsen, R. K. The role of anterior and medial dorsal thalamus in associative memory encoding and retrieval. Neuropsychologia 148, 107623 (2020).

    Article  PubMed  Google Scholar 

  131. Spets, D. S. & Slotnick, S. D. Thalamic functional connectivity during spatial long-term memory and the role of sex. Brain Sci. 10, 898 (2020).

    Article  PubMed Central  Google Scholar 

  132. Kafkas, A., Mayes, A. R. & Montaldi, D. Thalamic-medial temporal lobe connectivity underpins familiarity memory. Cereb. Cortex 30, 3827–3837 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  133. Pergola, G., Ranft, A., Mathias, K. & Suchan, B. The role of the thalamic nuclei in recognition memory accompanied by recall during encoding and retrieval: an fMRI study. Neuroimage 74, 195–208 (2013).

    Article  PubMed  Google Scholar 

  134. Su, J. H. et al. Thalamus optimized multi atlas segmentation (Thomas): fast, fully automated segmentation of thalamic nuclei from structural MRI. Neuroimage 194, 272–282 (2019).

    Article  PubMed  Google Scholar 

  135. Choi, S. H., Kim, Y. B., Paek, S. H. & Cho, Z. H. Papez circuit observed by in vivo human brain with 7.0T MRI super-resolution track density imaging and track tracing. Front. Neuroanat. 13, 17 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  136. Iglehart, C., Monti, M., Cain, J., Tourdias, T. & Saranathan, M. A systematic comparison of structural-, structural connectivity-, and functional connectivity-based thalamus parcellation techniques. Brain Struct. Funct. 225, 1631–1642 (2020).

    Article  PubMed  Google Scholar 

  137. Albo, Z., Di Prisco, G. V. & Vertes, R. P. Anterior thalamic unit discharge profiles and coherence with hippocampal theta rhythm. Thal. Relat. Syst. 2, 133–144 (2003).

    Google Scholar 

  138. Phillips, J. W. et al. A repeated molecular architecture across thalamic pathways. Nat. Neurosci. 22, 1925–1935 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Aggleton, J. P., Hunt, P. R., Nagle, S. & Neave, N. The effects of selective lesions within the anterior thalamic nuclei on spatial memory in the rat. Behav. Brain Res. 81, 189–198 (1996).

    Article  CAS  PubMed  Google Scholar 

  140. Byatt, G. & Dalrymple-Alford, J. C. Both anteromedial and anteroventral thalamic lesions impair radial-maze learning in rats. Behav. Neurosci. 110, 1335–1348 (1996).

    Article  CAS  PubMed  Google Scholar 

  141. Wilton, L. A. K., Baird, A. L., Muir, J. L., Honey, R. C. & Aggleton, J. P. Loss of the thalamic nuclei for “head direction” impairs performance on spatial memory tasks in rats. Behav. Neurosci. 115, 861–869 (2001).

    Article  CAS  PubMed  Google Scholar 

  142. Cullen, K. E. & Taube, J. S. Our sense of direction: progress, controversies and challenges. Nat. Neurosci. 20, 1465–1473 (2017).

    Article  CAS  PubMed  Google Scholar 

  143. Viejo, G. & Peyrache, A. Precise coupling of the thalamic head-direction system to hippocampal ripples. Nat. Commun. 11, 1–14 (2020).

    Article  CAS  Google Scholar 

  144. van Groen, T., Kadish, I. & Wyss, J. M. Efferent connections of the anteromedial nucleus of the thalamus of the rat. Brain Res. Rev. 30, 1–26 (1999).

    Article  PubMed  Google Scholar 

  145. Barbas, H., Henion, T. H. & Dermon, C. R. Diverse thalamic projections to the prefrontal cortex in the rhesus monkey. J. Comp. Neurol. 313, 65–94 (1991).

    Article  CAS  PubMed  Google Scholar 

  146. Shibata, H. & Naito, J. Organization of anterior cingulate and frontal cortical projections to the anterior and laterodorsal thalamic nuclei in the rat. Brain Res. 1059, 93–103 (2005).

    Article  CAS  PubMed  Google Scholar 

  147. Wolff, M., Gibb, S. J. & Dalrymple-Alford, J. C. Beyond spatial memory: the anterior thalamus and memory for the temporal order of a sequence of odor cues. J. Neurosci. 26, 2907–2913 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Dumont, J. R. & Aggleton, J. P. Dissociation of recognition and recency memory judgments after anterior thalamic nuclei lesions in rats. Behav. Neurosci. 127, 415–431 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  149. Bubb, E. J., Aggleton, J. P., O’Mara, S. M. & Nelson, A. J. Chemogenetics reveal an anterior cingulate–thalamic pathway for attending to task-relevant information. Cereb. Cortex 31, 2169–2186 (2021).

    Article  PubMed  Google Scholar 

  150. Kim, S. M., Ganguli, S. & Frank, L. M. Spatial information outflow from the hippocampal circuit: distributed spatial coding and phase precession in the subiculum. J. Neurosci. 32, 11539–11558 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Poulter, S., Lee, S. A., Dachtler, J., Wills, T. J. & Lever, C. Vector trace cells in the subiculum of the hippocampal formation. Nat. Neurosci. 24, 266–275 (2021).

    Article  CAS  PubMed  Google Scholar 

  152. Tsanov, M. et al. Hippocampal inputs mediate theta-related plasticity in anterior thalamus. Neuroscience 187, 52–62 (2011).

    Article  CAS  PubMed  Google Scholar 

  153. Dillingham, C. M. et al. Mammillothalamic disconnection alters hippocampocortical oscillatory activity and microstructure: implications for diencephalic amnesia. J. Neurosci. 39, 6696–6713 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Frost, B. E. et al. Anterior thalamic function is required for spatial coding in the subiculum and is necessary for spatial memory. J. Neurosci. 41, 6511–6525 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Hani, S. A. H. B., Al-Haidari, M. H. & Saboba, M. M. Neuronal types in the human anterior ventral thalamic nucleus: a Golgi study. Cell. Mol. Neurobiol. 27, 745–755 (2007).

    Article  PubMed  Google Scholar 

  156. Gaffan, D. & Gaffan, E. A. Amnesia in man following transection of the fornix: a review. Brain 114, 2611–2618 (1991).

    Article  PubMed  Google Scholar 

  157. Aggleton, J. P. et al. Differential cognitive effects of colloid cysts in the third ventricle that spare or compromise the fornix. Brain 123, 800–815 (2000).

    Article  PubMed  Google Scholar 

  158. Warburton, E. C., Baird, A. L., Morgan, A., Muir, J. L. & Aggleton, J. P. Disconnecting hippocampal projections to the anterior thalamus produces deficits on tests of spatial memory in rats. Eur. J. Neurosci. 12, 1714–1726 (2000).

    Article  CAS  PubMed  Google Scholar 

  159. Henry, J., Petrides, M., St-Laurent, M. & Sziklas, V. Spatial conditional associative learning: effects of thalamo-hippocampal disconnection in rats. Neuroreport 15, 2427–2431 (2004).

    Article  PubMed  Google Scholar 

  160. Kitanishi, T., Umaba, R. & Mizuseki, K. Robust information routing by dorsal subiculum neurons. Sci. Adv. 7, eabf1913 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  161. Rudebeck, S. R. et al. Fornix microstructure correlates with recollection but not familiarity memory. J. Neurosci. 29, 14987–14992 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Metzler-Baddeley, C., Jones, D. K., Belaroussi, B., Aggleton, J. P. & O’Sullivan, M. J. Frontotemporal connections in episodic memory and aging: a diffusion MRI tractography study. J. Neurosci. 31, 13236–13245 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Hartopp, N. et al. A key role for subiculum-fornix connectivity in recollection in older age. Front. Syst. Neurosci. 12, 70 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  164. Hodgetts, C. J. et al. The role of the fornix in human navigational learning. Cortex 124, 97–110 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  165. Christiansen, K. et al. The status of the precommissural and postcommissural fornix in normal ageing and mild cognitive impairment: an MRI tractography study. NeuroImage 130, 35–47 (2016).

    Article  PubMed  Google Scholar 

  166. Coad, B. M. et al. Precommissural and postcommissural fornix microstructure in healthy aging and cognition. Brain Neurosci. Adv. 4, 2398212819899316 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  167. Commins, S., Gigg, J., Anderson, M. & O’Mara, S. M. Interaction between paired-pulse facilitation and long-term potentiation in the projection from hippocampal area CA1 to the subiculum. Neuroreport 9, 4109–4113 (1998).

    Article  CAS  PubMed  Google Scholar 

  168. Liu, J. et al. Anterior thalamic stimulation improves working memory precision judgments. Brain Stim 14, 1073–1080 (2021).

    Article  Google Scholar 

  169. Xiao, D. & Barbas, H. Pathways for emotions and memory II. Afferent input to the anterior thalamic nuclei from prefrontal, temporal, hypothalamic areas and the basal ganglia in the rhesus monkey. Thal. Relat. Syst. 2, 33–48 (2002).

    Google Scholar 

  170. Jones, B. F. & Witter, M. P. Cingulate cortex projections to the parahippocampal region and hippocampal formation in the rat. Hippocampus 17, 957–976 (2007).

    Article  PubMed  Google Scholar 

  171. Sugar, J., Witter, M. P., van Strien, N. & Cappaert, N. The retrosplenial cortex: intrinsic connectivity and connections with the (para) hippocampal region in the rat. An interactive connectome. Front. Neuroinf. 5, 7 (2011).

    Article  Google Scholar 

  172. Dillingham, C. M., Milczarek, M. M., Perry, J. C. & Vann, S. D. Time to put the mammillothalamic pathway into context. Neurosci. Biobehav. Rev. 121, 60–74 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  173. Poirier, G. L. et al. Anterior thalamic lesions produce chronic and profuse transcriptional de-regulation in retrosplenial cortex: a model of retrosplenial hypoactivity and covert pathology. Thal. Relat. Syst. 4, 59–77 (2008).

    CAS  Google Scholar 

  174. Poirier, G. L. & Aggleton, J. P. Post-surgical interval and lesion location within the limbic thalamus determine extent of retrosplenial cortex hypoactivity. Neuroscience 160, 452–469 (2009).

    Article  CAS  PubMed  Google Scholar 

  175. Vann, S. D. Dismantling the Papez circuit for memory in rats. Elife 2, e00736 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  176. Yamawaki, N., Corcoran, K. A., Guedea, A. L., Shepherd, G. M. & Radulovic, J. Differential contributions of glutamatergic hippocampal→retrosplenial cortical projections to the formation and persistence of context memories. Cereb. Cortex 29, 2728–2736 (2019).

    Article  PubMed  Google Scholar 

  177. Aggleton, J. P. Multiple anatomical systems embedded within the primate medial temporal lobe: implications for hippocampal function. Neurosci. Biobehav. Rev. 36, 1579–1596 (2012).

    Article  PubMed  Google Scholar 

  178. Jay, T. M. & Witter, M. P. Distribution of hippocampal CA1 and subicular efferents in the prefrontal cortex of the rat studied by means of anterograde transport of Phaseolus vulgaris-leucoagglutinin. J. Comp. Neurol. 313, 574–586 (1991).

    Article  CAS  PubMed  Google Scholar 

  179. Raichle, M. E. The brain’s default mode network. Ann. Rev. Neurosci. 38, 433–447 (2015).

    Article  CAS  PubMed  Google Scholar 

  180. Mak, L. E. et al. The default mode network in healthy individuals: a systematic review and meta-analysis. Brain Conn. 7, 25–33 (2017).

    Article  Google Scholar 

  181. Andrews-Hanna, J. R., Reidler, J. S., Sepulcre, J., Poulin, R. & Buckner, R. L. Functional-anatomic fractionation of the brain’s default network. Neuron 65, 550–562 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Wen, T., Mitchell, D. J. & Duncan, J. The functional convergence and heterogeneity of social, episodic, and self-referential thought in the default mode network. Cereb. Cortex 30, 5915–5929 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  183. Yeshurun, Y., Nguyen, M. & Hasson, U. The default mode network: where the idiosyncratic self meets the shared social world. Nat. Rev. Neurosci. 22, 181–192 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Buckner, R. L., Andrews-Hanna, J. R. & Schacter, D. L. in The Year in Cognitive Neuroscience (eds. Kingstone, A. & Miller, M. B.) 1–38 (Blackwell, 2008).

  185. Schacter, D. L., Addis, D. R. & Buckner, R. L. Remembering the past to imagine the future: the prospective brain. Nat. Rev. Neurosci. 8, 657–661 (2007).

    Article  CAS  PubMed  Google Scholar 

  186. Schacter, D. L. et al. The future of memory: remembering, imagining, and the brain. Neuron 76, 677–694 (2012).

    Article  CAS  PubMed  Google Scholar 

  187. Alves, P. N. et al. An improved neuroanatomical model of the default-mode network reconciles previous neuroimaging and neuropathological findings. Comm. Biol. 2, 370 (2019).

    Article  Google Scholar 

  188. Li, J. et al. Mapping the subcortical connectivity of the human default mode network. NeuroImage 245, 118758 (2021).

    Article  PubMed  Google Scholar 

  189. Jones, D. T., Mateen, F. J., Lucchinetti, C. F., Jack, C. R. & Welker, K. M. Default mode network disruption secondary to a lesion in the anterior thalamus. Arch. Neurol. 68, 242–247 (2011).

    Article  PubMed  Google Scholar 

  190. Middlebrooks, E. H. et al. Functional activation patterns of deep brain stimulation of the anterior nucleus of the thalamus. World Neurosurg. 136, 357–363 (2020).

    Article  PubMed  Google Scholar 

  191. Kaboodvand, N., Bäckman, L., Nyberg, L. & Salami, A. The retrosplenial cortex: a memory gateway between the cortical default mode network and the medial temporal lobe. Hum. Brain Map. 39, 2020–2034 (2018).

    Article  Google Scholar 

  192. Garden, D. L. et al. Anterior thalamic lesions stop synaptic plasticity in retrosplenial cortex slices: expanding the pathology of diencephalic amnesia. Brain 132, 1847–1857 (2009).

    Article  PubMed  Google Scholar 

  193. Williams, A. N. et al. The role of the pre-commissural fornix in episodic autobiographical memory and simulation. Neuropsychologia 142, 107457 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  194. Corkin, S. Beware of frontal lobe deficits in hippocampal clothing. Trends Cogn. Sci. 5, 321–323 (2001).

    Article  CAS  PubMed  Google Scholar 

  195. Hermann, B. & Seidenberg, M. Executive system dysfunction in temporal lobe epilepsy: effects of nociferous cortex versus hippocampal pathology. J. Clin. Exp. Neuropsych 17, 809–819 (1995).

    Article  CAS  Google Scholar 

  196. Pearce, J. M. & Mackintosh, N. J. in Attention and Associative Learning: From Brain to Behaviour (eds. Mitchell, C. & Le Pelley, M.) 11–39 (Oxford Univ. Press, 2010).

  197. Dias, R., Robbins, T. W. & Roberts, A. C. Dissociation in prefrontal cortex of affective and attentional shifts. Nature 380, 69–72 (1996).

    Article  CAS  PubMed  Google Scholar 

  198. Birrell, J. M. & Brown, V. J. Medial frontal cortex mediates perceptual attentional set shifting in the rat. J. Neurosci. 20, 4320–4324 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Barbas, H. & Zikopoulos, B. The prefrontal cortex and flexible behavior. Neuroscientist 13, 532–545 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  200. Marquis, J. P., Goulet, S. & Doré, F. Y. Neonatal ventral hippocampus lesions disrupt extra-dimensional shift and alter dendritic spine density in the medial prefrontal cortex of juvenile rats. Neurobiol. Learn. Mem. 90, 339–346 (2008).

    Article  PubMed  Google Scholar 

  201. Nelson, A. J. The anterior thalamic nuclei and cognition: a role beyond space? Neurosci. Biobehav. Rev. 126, 1–11 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  202. Wolff, M., Alcaraz, F., Marchand, A. R. & Coutureau, E. Functional heterogeneity of the limbic thalamus: from hippocampal to cortical functions. Neurosci. Biobehav. Rev. 54, 120–130 (2015).

    Article  PubMed  Google Scholar 

  203. Albasser, M. M., Amin, E., Lin, T. C. E., Iordanova, M. D. & Aggleton, J. P. Evidence that the rat hippocampus has contrasting roles in object recognition memory and object recency memory. Behav. Neurosci. 126, 659–669 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  204. Dupire, A. et al. A role for anterior thalamic nuclei in affective cognition: interaction with environmental conditions. Hippocampus 23, 392–404 (2013).

    Article  CAS  PubMed  Google Scholar 

  205. Gabriel, M. & Talk, A. C. in Model Systems and the Neurobiology of Associative Learning: A Festschrift in Honor of Richard F. Thompson (eds. Steinmetz, J. E. Gluck, M. A. & Solomon, P. R.) 149–185 (Lawrence Erlbaum, 2001).

  206. Shin, J. N., Doron, G. & Larkum, M. E. Memories off the top of your head. Science 374, 538–539 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Witter, M. P. & Groenewegen, H. J. Connections of the parahippocampal cortex in the cat. III. Cortical and thalamic efferents. J. Comp. Neurol. 252, 1–31 (1986).

    Article  CAS  PubMed  Google Scholar 

  208. Brennan, E. K. et al. Thalamus and claustrum control parallel layer 1 circuits in retrosplenial cortex. eLife 10, e62207 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Kinnavane, L., Vann, S. D., Nelson, A. J., O’Mara, S. M. & Aggleton, J. P. Collateral projections innervate the mammillary bodies and retrosplenial cortex: a new category of hippocampal cells. eNeuro 5, ENEURO.0383-17.2018 2018.

  210. Zoppelt, D., Koch, B., Schwarz, M. & Daum, I. Involvement of the mediodorsal thalamic nucleus in mediating recollection and familiarity. Neuropsychologia 41, 1160–1170 (2003).

    Article  PubMed  Google Scholar 

  211. Danet, L. et al. Medial thalamic stroke and its impact on familiarity and recollection. Elife 6, e28141 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  212. Carlesimo, G. A., Lombardi, M. G., Caltagirone, C. & Barban, F. Recollection and familiarity in the human thalamus. Neurosci. Biobehav. Rev. 54, 18–28 (2015).

    Article  PubMed  Google Scholar 

  213. Grodd, W., Kumar, V. J., Schüz, A., Lindig, T. & Scheffler, K. The anterior and medial thalamic nuclei and the human limbic system: tracing the structural connectivity using diffusion-weighted imaging. Sci. Rep. 10, 10957 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Gagnepain, P. et al. Collective memory shapes the organization of individual memories in the medial prefrontal cortex. Nat. Hum. Behav. 4, 189–200 (2020).

    Article  PubMed  Google Scholar 

  215. Barnett, S. C. et al. Anterior thalamic nuclei neurons sustain memory. Curr. Res. Neurobiol. 2, 100022 (2021).

    Article  CAS  Google Scholar 

  216. Swanson, L. W. & Cowan, W. M. An autoradiographic study of the organization of the efferent connections of the hippocampal formation in the rat. J. Comp. Neurol. 172, 49–84 (1977).

    Article  CAS  PubMed  Google Scholar 

  217. van Groen, T. & Wyss, J. M. Connections of the retrosplenial granular a cortex in the rat. J. Comp. Neurol. 300, 593–606 (1990).

    Article  PubMed  Google Scholar 

  218. van Groen, T. & Wyss, J. M. Connections of the retrosplenial dysgranular cortex in the rat. J. Comp. Neurol. 315, 200–216 (1992).

    Article  PubMed  Google Scholar 

  219. Shibata, H. Topographic organization of subcortical projections to the anterior thalamic nuclei in the rat. J. Comp. Neurol. 323, 117–127 (1992).

    Article  CAS  PubMed  Google Scholar 

  220. Lozsádi, D. A. Organization of connections between the thalamic reticular and the anterior thalamic nuclei in the rat. J. Comp. Neurol. 358, 233–246 (1995).

    Article  PubMed  Google Scholar 

  221. Bartsch, T. & Butler, C. Transient amnesic syndromes. Nat. Rev. Neurol. 9, 86–97 (2013).

    Article  CAS  PubMed  Google Scholar 

  222. Jankowski, M. M. et al. The anterior thalamus provides a subcortical circuit supporting memory and spatial navigation. Front. Syst. Neurosci. 7, 45 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

J.P.A. and S.M.O’M. are supported in the work described here by the Wellcome Trust (103722/Z14/Z). We thank S. Commins, S. Martin, A. Nelson and C. Ranganath for very helpful feedback on a prior version of the manuscript. We also thank M. M. Jankowski for assistance with Fig. 1.

Author information

Authors and Affiliations

Authors

Contributions

The authors contributed equally to all aspects of the article.

Corresponding authors

Correspondence to John P. Aggleton or Shane M. O’Mara.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Neuroscience thanks J. Dalrymple-Alford, M. Wolff 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.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aggleton, J.P., O’Mara, S.M. The anterior thalamic nuclei: core components of a tripartite episodic memory system. Nat Rev Neurosci 23, 505–516 (2022). https://doi.org/10.1038/s41583-022-00591-8

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41583-022-00591-8

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