The mammillary bodies: two memory systems in one?

Key Points

  • It has long been supposed that the mammillary bodies contribute to learning and memory, although the importance of these nuclei and the nature of their contributions have remained poorly understood. Recent electrophysiological data, combined with an appreciation of the anatomical connections of this region, provide a new framework within which to examine this diencephalic region.

  • The mammillary bodies can be divided on cytoarchitectonic and connectional grounds into a lateral and a medial division. The lateral and medial mammillary nuclei are connected with the same regions (anterior thalamic nuclei, Gudden's tegmental nuclei, the hippocampal formation), but with different subfields or nuclei within these regions. This pattern suggests the presence of two parallel systems, which might have different functions but nevertheless contribute to the same classes of learning.

  • The lateral mammillary nucleus contains head direction cells that signal the horizontal orientation of an animal. The activity of these cells is necessary for the anterior thalamic head direction signal, which is in turn crucial for head direction signals in the hippocampal formation. The medial mammillary nucleus contains theta-related cells that are thought to reflect hippocampal activity, and are assumed to relay to the anterior thalamic nuclei. Theta is assumed to act as a 'significance signal', so that information arriving with theta activity is more likely to be stored.

  • The effects of selective mammillary body lesions in animals consistently point to the involvement of this region in the encoding of spatial information. It is argued that the medial and lateral nuclei contribute in different ways so that they complement each other. Although this assumption remains to be tested directly, it is known that the effects of selective lesions in the anterior thalamic nuclei, to which the mammillary bodies project, are additive. These data support the notion of two distinct, but related, functions.

  • Clinical studies into the effects of mammillary body damage indicate that this region is necessary for the normal recall of episodic information. This conclusion is reinforced by recent studies revealing the importance for memory of the mammillothalamic tract, the main output route from the mammillary bodies. The severity of the memory loss associated with mammillary body damage depends upon the extent of damage to other diencephalic regions, key amongst these being the anterior thalamic nuclei.

  • It is proposed that the mammillary bodies permit the integration of orientation information and theta, so enable the storing of scene information. These twin roles aid episodic recall.

Abstract

Although the mammillary bodies have been implicated in amnesia perhaps for longer than any other single brain region, their role has remained elusive. It is now emerging that the difficulties in understanding the importance of the mammillary bodies for memory might stem from the tradition of treating the mammillary bodies as a single structure with a single function. This review will dissect the mammillary bodies and show how their component nuclei might have multiple functions that, nevertheless, are coordinated to give the impression of a unitary function.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Photomicrographs of the mammillary nuclei.
Figure 2
Figure 3: The lateral mammillary nucleus and head direction information.
Figure 4: The medial mammillary nucleus and theta rhythm.
Figure 5: Magnetic resonance scans showing the absence of the mammillary bodies in patient B.J.

References

  1. 1

    Gudden, H. Klinische und anatomische beitrage zur kenntnis der multiplen Alkoholneuritis nebst bemärkungen über die Regerationsvorgänge in peripheren Nervensystem. Archiv. für Psychiatrie und Nervenkrankheiten 28, 643–741 (1896).

    Google Scholar 

  2. 2

    Gamper, E. Zur Frage der Polioencephalitis der chronischen Alkoholiker. Anatomische Befunde beim chronischem Korsakow und ihre Beziehungen zum klinischen Bild. Deutsche Z. Nervenheilkd. 102, 122–129 (1928).

    Google Scholar 

  3. 3

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

    Google Scholar 

  4. 4

    Kahn, E. A. & Crosby, E. C. Korsakoff's syndrome associated with surgical lesions involving the mammillary bodies. Neurology 22, 117–125 (1972).

    CAS  PubMed  Google Scholar 

  5. 5

    Dusoir, H., Kapur, N., Brynes, D. P., McKinstry, S. & Hoare, R. D. The role of diencephalic pathology in human memory disorder. Brain 113, 1695–1706 (1990). Patient B.J., who suffered a discrete mammillary body lesion as a result of a penetrating brain injury, is described. B.J. showed a marked verbal memory impairment, whereas nonverbal memory was less affected and additional tests of cognitive ability showed no impairment.

    PubMed  Google Scholar 

  6. 6

    Blair, H. T., Cho, J. & Sharp, P. E. Role of the lateral mammillary nucleus in the rat head-direction circuit: a combined single unit recording and lesion study. Neuron 21, 1387–1397 (1998). Head direction cell recordings were made in the anterior thalamus and lateral mammillary nuclei. The head direction signal in the lateral mammillary bodies preceded that in the anterior thalamus by about 15–20 ms. After bilateral lesions of the lateral mammillary nuclei, the head direction cells in the anterior thalamus permanently lost their directional firing properties.

    CAS  PubMed  Google Scholar 

  7. 7

    Blair, H. T., Cho, J. & Sharp, P. E. The anterior thalamic head-direction signal is abolished by bilateral but not unilateral lesions of the lateral mammillary nucleus. J. Neurosci. 19, 6673–6683 (1999).

    CAS  PubMed  Google Scholar 

  8. 8

    Stackman, R. W. & Taube, J. S. Firing properties of rat lateral mammillary single units: head direction, head pitch, and angular head velocity. J. Neurosci. 18, 9020–9037 (1998). Single neuron recordings in the lateral mammillary nucleus showed that most cells fired as a function of directional heading, head pitch or angular head velocity. Cells were found to anticipate the rat's future head direction by about 65 ms.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9

    Van der Werf, Y. 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). Patients with thalamic infarcts underwent neuropsychological tests and a lesion overlap study. Mammillothalamic tract damage was associated with impaired episodic memory, with relative sparing of intelligence and short-term memory.

    PubMed  Google Scholar 

  10. 10

    Crosby, E. C. & Showers, M. J. C. in The Hypothalamus (eds Haymaker, W., Anderson, E. & Nauta, W. J. H.) 61–134 (Charles C. Thomas, Illinois, 1969).

    Google Scholar 

  11. 11

    Rose, J. The cell structure of the mamillary body in man. J. Anat. 74, 91–115 (1939).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12

    Kirk, I. J. Frequency modulation of hippocampal theta by the supramammillary nucleus, and other hypothalamo-hippocampal interactions: mechanisms and functional implications. Neurosci. Biobehav. Rev. 22, 291–302 (1998).

    CAS  PubMed  Google Scholar 

  13. 13

    Pan, W. -X. & McNaughton, N. The medial supramammillary nucleus, spatial learning and the frequency of hippocampal theta activity. Brain Res. 764, 101–108 (1997).

    CAS  PubMed  Google Scholar 

  14. 14

    Pan, W. -X. & McNaughton, N. The role of the medial supramammillary nucleus in the control of hippocampal theta activity and behaviour in rats. Eur. J. Neurosci. 16, 1797–1809 (2002).

    PubMed  Google Scholar 

  15. 15

    Breathnach, A. S. & Goldby, F. The amygdaloid nuclei, hippocampus and other parts of the rhinencephalon in the porpoise (Phocaena phocaena). J. Anat. 88, 267–291 (1954).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16

    Allen, G. V. & Hopkins, D. A. Mamillary body in the rat: a cytoarchitectonic, Golgi, and ultrastructural study. J. Comp. Neurol. 275, 39–64 (1988).

    CAS  PubMed  Google Scholar 

  17. 17

    Christ, J. F. in The Hypothalamus (eds Haymaker, W., Anderson, E. & Nauta, W. J. H.) 13–38 (Charles C. Thomas, Illinois, 1969).

    Google Scholar 

  18. 18

    Veazey, R. B., Amaral, D. G. & Cowan, M. W. The morphology and connections of the posterior hypothalamus in the Cynomolgus Monkey (Macaca fascicularis). I. Cytoarchitectonic organisation. J. Comp. Neurol. 207, 114–134 (1982).

    CAS  PubMed  Google Scholar 

  19. 19

    Nauta, W. J. H. & Haymaker, W. in The Hypothalamus (eds Haymaker, W., Anderson, E. & Nauta, W. J. H.) 136–203 (Charles C. Thomas, Illinois, 1969).

    Google Scholar 

  20. 20

    Allen, G. V. & Hopkins, D. A. Mamillary body in the rat: topography and synaptology of projections from the subicular complex, prefrontal cortex, and midbrain tegmentum. J. Comp. Neurol. 286, 311–336 (1989).

    CAS  PubMed  Google Scholar 

  21. 21

    Gonzalo-Ruiz, A., Alonso, A., Sanz, J. M. & Llinas, R. R. Afferent projections to the mammillary complex of the rat, with special reference to those surrounding hypothalamic regions. J. Comp. Neurol. 321, 277–299 (1992).

    CAS  PubMed  Google Scholar 

  22. 22

    Meibach, R. C. & Siegel, A. Efferent connections of the hippocampal formation in the rat. Brain Res. 124, 197–224 (1977).

    CAS  PubMed  Google Scholar 

  23. 23

    Shibata, H. A direct projection from the entorhinal cortex to the mammillary nuclei in the rat. Neurosci. Lett. 90, 6–10 (1988).

    CAS  PubMed  Google Scholar 

  24. 24

    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).

    CAS  PubMed  Google Scholar 

  25. 25

    Van Groen, T. & Wyss, J. M. The postsubicular cortex in the rat: characterization of the fourth region of the subicular cortex and its connections. Brain Res. 529, 165–177 (1990).

    CAS  PubMed  Google Scholar 

  26. 26

    Risold, P. Y. & Swanson, L. W. Structural evidence for functional domains in the rat hippocampus. Science 272, 1484–1486 (1996).

    CAS  PubMed  Google Scholar 

  27. 27

    Cruce, J. A. F. An autoradiographic study of the projections of the mammillothalamic tract in the rat. Brain Res. 85, 211–219 (1975).

    CAS  PubMed  Google Scholar 

  28. 28

    Seki, M. & Zyo, K. Anterior thalamic afferents from the mamillary body and the limbic cortex in the rat. J. Comp. Neurol. 229, 242–256 (1984).

    CAS  PubMed  Google Scholar 

  29. 29

    Watanabe, K. & Kawana, E. A horseradish peroxidase study on the mammillothalamic tract in the rat. Acta Anat. 108, 394–401 (1980).

    CAS  PubMed  Google Scholar 

  30. 30

    Cruce, J. A. F. An autoradiographic study of descending connections of the mammillary nuclei of the rat. J. Comp. Neurol. 176, 631–644 (1977).

    CAS  PubMed  Google Scholar 

  31. 31

    Hayakawa, T. & Zyo, K. Comparative anatomical study of the tegmentomammillary projections in some mammals: a horseradish peroxidase study. Brain Res. 300, 335–349 (1984).

    CAS  PubMed  Google Scholar 

  32. 32

    Hayakawa, T. & Zyo, K. Afferent connections of Gudden's tegmental nuclei in the rabbit. J. Comp. Neurol. 235, 169–181 (1985).

    CAS  PubMed  Google Scholar 

  33. 33

    Allen, G. V. & Hopkins, D. A. Topography and synaptology of mamillary body projections to the mesencephalon and pons in the rat. J. Comp. Neurol. 301, 214–231 (1990).

    CAS  PubMed  Google Scholar 

  34. 34

    Poletti, C. E. & Creswell, G. Fornix system efferent projections in the squirrel monkey: an experimental degeneration study. J. Comp. Neurol. 175, 101–127 (1977).

    CAS  PubMed  Google Scholar 

  35. 35

    Veazey, R. B., Amaral, D. G. & Cowan, M. W. The morphology and connections of the posterior hypothalamus in the Cynomolgus Monkey (Macaca fascicularis). II. Efferent connection. J. Comp. Neurol. 207, 135–156 (1982).

    CAS  PubMed  Google Scholar 

  36. 36

    Aggleton, J. P. & Brown, M. W. Episodic memory, amnesia and the hippocampal anterior thalamic axis. Behav. Brain Sci. 22, 425–466 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37

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

    PubMed  Google Scholar 

  38. 38

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

    PubMed  Google Scholar 

  39. 39

    Van der Werf, Y., Witter, M. P., Uylings, H. B. M. & Jolles, J. Neuropsychology of infarctions in the thalamus: a review. Neuropsychologia 38, 613–627 (2000).

    CAS  PubMed  Google Scholar 

  40. 40

    Barbizet, J. Defect of memorising of hippocampal-mammillary origin: a review. J. Neurol. Neurosurg. Psychiat. 26, 127–135 (1963).

    CAS  PubMed  Google Scholar 

  41. 41

    Aggleton, J. P., Hunt, P. R. & Shaw, C. The effects of mammillary body and combined amygdalar-fornix lesions on tests of delayed non-matching-to-sample in the rat. Behav. Brain Res. 40, 145–157 (1990).

    CAS  PubMed  Google Scholar 

  42. 42

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

    CAS  PubMed  Google Scholar 

  43. 43

    Béracochéa, D. J. & Jaffard, R. The effects of mammillary body lesions on delayed matching and delayed non-matching to place tasks in the mice. Behav. Brian Res. 68, 45–52 (1995).

    Google Scholar 

  44. 44

    Béracochéa, D. J. & Jaffard, R. Impairment of spontaneous alternation behavior in sequential test procedures following mammillary body lesions in mice: evidence for time-dependent interference-related memory deficits. Behav. Neurosci. 101, 187–197 (1987).

    PubMed  Google Scholar 

  45. 45

    Field, T. D., Rosenstock, J., King, E. C. & Greene, E. Behavioral role of the mammillary efferent system. Brain Res. Bull. 3, 451–456 (1978).

    CAS  PubMed  Google Scholar 

  46. 46

    Gaffan, E. A., Bannerman, D. M., Warburton, E. C. & Aggleton, J. P. Rats' processing of visual scenes: effects of lesions to fornix, anterior thalamus, mammillary nuclei or the retrohippocampal region. Behav. Brain Res. 121, 103–117 (2001).

    CAS  PubMed  Google Scholar 

  47. 47

    Rosenstock, J., Field, T. D. & Greene, E. The role of the mammillary bodies in spatial memory. Exp. Neurol. 55, 340–352 (1977).

    CAS  PubMed  Google Scholar 

  48. 48

    Thomas, G. J. & Gash, D. M. Mammillothalamic tracts and representational memory. Behav. Neurosci. 99, 621–630 (1985).

    CAS  PubMed  Google Scholar 

  49. 49

    Vann, S. D. & Aggleton, J. P. Evidence of a spatial encoding deficit in rats with lesions of the mammillary bodies or mammillothalamic tract. J. Neurosci. 23, 3506–3514 (2003). Rats with neurotoxic mammillary body or mammillothalamic tract lesions were tested on spatial memory tasks in the T-maze, radial-arm maze and water maze. Both types of lesion impaired acquisition of these tasks but subsequent performance was not differentially affected when retention delays or levels of interference were introduced. The results point to a deficit in allocentric spatial encoding.

    CAS  PubMed  Google Scholar 

  50. 50

    Saravis, S., Sziklas, V. & Petrides, M. Memory for places and the region of the mammillary bodies in rats. Eur. J. Neurosci. 2, 556–564 (1990).

    PubMed  Google Scholar 

  51. 51

    Sziklas, V., Petrides, M. & Leri, F. The effects of lesions to the mammillary region and the hippocampus on conditional associative learning by rats. Eur. J. Neurosci. 8, 106–115 (1996).

    CAS  PubMed  Google Scholar 

  52. 52

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

    CAS  PubMed  Google Scholar 

  53. 53

    Santín, L. J., Rubio, S., Begaga, A. & Arias, J. L. Effects of mammillary body lesions on spatial reference and working memory tasks. Behav. Brain Res. 102, 137–150 (1999). Electrolytic mammillary body lesions in rats did not impair reference memory in the water maze, but significantly impaired working memory. The lesion group was not differentially affected by increased retention delays.

    PubMed  Google Scholar 

  54. 54

    Holmes, E. J., Jacobson, S., Stein, B. M. & Butters, N. Ablations of the mammillary nuclei in monkeys: effects on postoperative memory. Exp. Neurol. 81, 97–113 (1983).

    CAS  PubMed  Google Scholar 

  55. 55

    Holmes, E. J., Butters, N., Jacobson, S. & Stein, B. M. An examination of the effects of mammillary-body lesions on reversal learning sets in monkeys. Physiol. Psychol. 11, 159–165 (1983).

    Google Scholar 

  56. 56

    Jaffard, R., Béracochéa, D. J. & Cho, Y. The hippocampal-mamillary system: anterograde and retrograde amnesia. Hippocampus 1, 275–278 (1991).

    CAS  PubMed  Google Scholar 

  57. 57

    Sziklas, V. & Petrides, M. Memory and the region of the mammillary bodies. Prog. Neurobiol. 54, 55–70 (1998). This analysis reviews the effects of mammillary body lesions (particularly electrolytic lesions) on rats' performances on spatial and non-spatial memory tasks. The authors conclude that the degree of impairment depends on the extent of mammillary body damage and the difficulty of the task. mammillary body damage was associated with a selective spatial memory impairment, whereas visual discrimination and recognition memory were unaffected.

    CAS  PubMed  Google Scholar 

  58. 58

    Aggleton, J. P., Keith, A. P. & Saghal, 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).

    CAS  PubMed  Google Scholar 

  59. 59

    Harper, D. N., McLean, A. P. & Dalrymple-Alford, J. C. Forgetting in rats following medial septum or mammillary body damage. Behav. Neurosci. 108, 691–702 (1994).

    CAS  PubMed  Google Scholar 

  60. 60

    Neave, N., Nagel, S. & Aggleton, J. P. Evidence for the involvement of the mammillary bodies and cingulum bundle in allocentric spatial processing by rats. Eur. J. Neurosci. 9, 941–955 (1997).

    CAS  PubMed  Google Scholar 

  61. 61

    Sziklas, V. & Petrides, M. Selectivity of the spatial learning deficit after lesions of the mammillary region in rats. Hippocampus 10, 325–328 (2000).

    CAS  PubMed  Google Scholar 

  62. 62

    Thompson, R. Rapid forgetting of a spatial habit in rats with hippocampal lesions. Science 212, 959–960 (1981).

    CAS  PubMed  Google Scholar 

  63. 63

    Vann, S. D., Honey, R. C. & Aggleton, J. P. Lesions of the mammillothalamic tract impair the acquisition of spatial but not nonspatial contextual conditional discriminations. Eur. J. Neurosci. 18, 2413–2416 (2003).

    PubMed  Google Scholar 

  64. 64

    Parker, A. & Gaffan, D. Mammillary body lesions in monkeys impair object-in-place memory: functional unity of the fornix-mamillary system. J. Cogn. Neurosci. 9, 512–521 (1997). Preoperatively trained monkeys were impaired at learning new scenes in an object-in-place memory task after mammillary body lesions. This impairment was equal to that seen after fornix lesions or combined fornix and mammillary body lesions.

    CAS  PubMed  Google Scholar 

  65. 65

    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).

    CAS  PubMed  Google Scholar 

  66. 66

    Aggleton, J. P. & Mishkin, M. Mamillary-body lesions and visual recognition in monkeys. Exp. Brain Res. 58, 190–197 (1985).

    CAS  PubMed  Google Scholar 

  67. 67

    Taube, J. S. Head direction cells and the neurophysiological basis for a sense of direction. Prog. Neurobiol. 55, 225–256 (1998).

    CAS  PubMed  Google Scholar 

  68. 68

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

    CAS  PubMed  Google Scholar 

  69. 69

    Sharp, P. E., Tinkelman, A. & Cho, J. Angular velocity and head direction signals recorded from the dorsal tegmental nucleus of Gudden in the rat: implications for path integration in the head direction cell circuit. Behav. Neurosci. 115, 571–588 (2001).

    CAS  PubMed  Google Scholar 

  70. 70

    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).

    CAS  PubMed  Google Scholar 

  71. 71

    Taube, J. S., Goodridge, J. P., Golob, E. J., Dudchenko, P. A. & Stackman, R. W. Processing the head direction cell signal: a review and commentary. Brain Res. Bull. 40, 477–486 (1996).

    CAS  PubMed  Google Scholar 

  72. 72

    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).

    CAS  PubMed  Google Scholar 

  73. 73

    Brown, J. E., Yates, B. J. & Taube, J. S. Does the vestibular system contribute to head direction cell activity in the rat? Phys. Behav. 77, 743–748 (2002).

    CAS  Google Scholar 

  74. 74

    Stackman, R. W. & Taube, J. S. Firing properties of head direction cells in rat anterior thalamic neurons: dependence on vestibular input. J. Neurosci. 17, 4349–4358 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. 75

    Dudchenko, P. A. & Taube, J. S. Correlation between head direction cell activity and spatial behaviour on a radial arm maze. Behav. Neurosci. 111, 3–19 (1997).

    CAS  PubMed  Google Scholar 

  76. 76

    Golob, E. J., Stackman, R. W., Wong, A. C. & Taube, J. S. On the behavioral significance of head direction cells: neural and behavioral dynamics during spatial memory tasks. Behav. Neurosci. 115, 285–305 (2001).

    CAS  PubMed  Google Scholar 

  77. 77

    Knierim, J. J., Kudrimoti, H. S. & McNaughton, B. L. Place cells, head direction cells, and the learning of landmark stability. J. Neurosci. 15, 1648–1659 (1995).

    CAS  Google Scholar 

  78. 78

    McNaughton, B. L. et al. Deciphering the hippocampal polyglot: the hippocampus as a path integration system. J. Exp. Biol. 199, 173–185 (1996).

    CAS  Google Scholar 

  79. 79

    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).

    CAS  PubMed  Google Scholar 

  80. 80

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

    CAS  PubMed  Google Scholar 

  81. 81

    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).

    PubMed  Google Scholar 

  82. 82

    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).

    CAS  PubMed  Google Scholar 

  83. 83

    Kahana, M. J., Sekuler, R., Caplan, J. B., Kirschen, M. & Madsen, J. R. Human theta oscillations exhibit task dependence during virtual maze navigation. Nature 399, 781–784 (1999).

    CAS  Google Scholar 

  84. 84

    O'Keefe, J. & Recce, M. Phase relationship between hippocampal place cell units and the EEG theta rhythm. Hippocampus 3, 317–330 (1993).

    CAS  Google Scholar 

  85. 85

    Bland, B. H., Konopacki, J., Kirk, I. J., Oddie, S. D. & Dickson, C. T. Discharge patterns of hippocampal theta-related cells in the caudal diencephalons of the urethane-anesthetized rat. J. Neurophys. 74, 322–333 (1995).

    CAS  Google Scholar 

  86. 86

    Komisaruk, B. R. Synchrony between limbic system theta activity and rhythmical behaviour in rats. J. Comp. Physiol. Psychol. 70, 482–492 (1970).

    CAS  PubMed  Google Scholar 

  87. 87

    Kocsis, B. & Vertes, R. P. Characterization of neurons of the supramammillary nucleus and mammillary body that discharge rhythmically with hippocampal theta in the rat. J. Neurosci. 14, 7040–7052 (1994). Theta-related neurons were found in the supramammillary nucleus and mammillary body of the rat. The theta-related cells in the mammillary body, but not the supramammillary nucleus, were correlated with the CA1 field of the hippocampus, consistent with the theta-related cells in the mammillary body being driven by the descending projections.

    CAS  PubMed  Google Scholar 

  88. 88

    Kirk, I. J., Oddie, S. D., Konopacki, J. & Bland, B. H. Evidence for differential control of posterior hypothalamic, supramammillary, and medial mammillary theta related cellular discharge by ascending and descending pathways. J. Neurosci. 16, 5547–5554 (1996).

    CAS  PubMed  Google Scholar 

  89. 89

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

    Google Scholar 

  90. 90

    Vertes, R. P., Albo, Z. & Viana Di Prisco, G. Theta-rhythmically firing neurons in the anterior thalamus: implications for mnemonic functions of Papez's circuit. Neuroscience 104, 619–625 (2001).

    CAS  PubMed  Google Scholar 

  91. 91

    Kocsis, B., Viana Di Prisco, G. & Vertes, R. P. Theta sychronization in the limbic system: the role of Gudden's tegmental nuclei. Eur. J. Neurosci. 13, 381–388 (2001).

    CAS  PubMed  Google Scholar 

  92. 92

    Llinás, R. R. & Alonso, A. Electrophysiology of the mammillary complex in vitro. I. Tuberomammillary and lateral mammillary neurons. J. Neurophysiol. 68, 1307–1320 (1992).

    PubMed  Google Scholar 

  93. 93

    Vertes, R. P. & Kocsis, B. Brainstem-diencephalo-septohippocampal systems controlling the theta rhythm of the hippocampus. Neuroscience 81, 893–926 (1997).

    CAS  Google Scholar 

  94. 94

    Hasselmo, M., Cannon, R. C. & Koene, R. in The Parahippocampal Region (eds Witter, M., Wouterlood, F.) 139–161 (Oxford Univ. Press, Oxford, 2002).

    Google Scholar 

  95. 95

    Cermak, L. S. & Butters, N. The role of interference and encoding in the short-term memory deficits of Korsakoff patients. Neuropsychologia 10, 89–95 (1972).

    CAS  PubMed  Google Scholar 

  96. 96

    Kapur, N. et al. in Neuropsychological Explorations of Memory and Cognition: Essays in Honor of Nelson Butters Critical issues in Neuropsychology (ed. Cermak, L.) 159–189 (Plenum, New York, 1994).

    Google Scholar 

  97. 97

    Holdstock, J. S., Shaw, C. & Aggleton, J. P. The performance of amnesic subjects on tests of delayed matching-to-sample and delayed matching-to-position. Neuropsychologia 33, 1583–1596 (1995).

    CAS  PubMed  Google Scholar 

  98. 98

    Butters, N. et al. Differentiation of amnesic and demented patients with the Wechsler Memory Scale — revised. Clin. Neuropsychol. 2, 133–148 (1988).

    Google Scholar 

  99. 99

    Aggleton, J. P. & Shaw, C. Amnesia and recognition memory: a re-analysis of psychometric data. Neuropsychologia 34, 51–62 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. 100

    Teuber, H. L., Milner, B. & Vaughan, H. G. Persistent anterograde amnesia after stab wound of basal brain. Neuropsychologia 6, 267–282 (1968).

    Google Scholar 

  101. 101

    Squire, L. R., Amaral, D. G., Zola-Morgan, S., Kritchevsky, M. & Press, G. Description of brain injury in the amnesic patient N. A. based on magnetic resonance imaging. Exp. Neurol. 105, 23–35 (1989).

    CAS  PubMed  Google Scholar 

  102. 102

    Hildebrandt, H., Muller, S., Bussmann-Mork, B., Goebel, S. & Eilers, N. Are some memory deficits unique to lesions of the mammillary bodies? J. Clin. Exp. Neuropsychol. 23, 490–501 (2001). A patient was reported who showed a severe memory impairment after surgery to remove a germinoma. An MRI showed an infarct of the left mammillary body and bilateral mammillary body shrinkage. This patient had impaired free and delayed recall but normal recognition memory, and impaired recency judgement and source recall.

    CAS  PubMed  Google Scholar 

  103. 103

    Tanaka, Y., Miyazawa, Y., Araoka, F. & Yamada, T. Amnesia following damage to the mammillary bodies. Neurology 4, 160–165 (1997).

    Google Scholar 

  104. 104

    Von Cramon, D. Y., Hebel, N. & Schuri, U. A contribution to the anatomical basis of thalamic amnesia. Brain 108, 993–1008 (1985).

    PubMed  Google Scholar 

  105. 105

    Clarke, S. et al. Pure amnesia after unilateral left polar thalamic infarct: topographic and sequential neuropsychological and metabolic (PET) correlations. J. Neurol. Neurosurg. Psychiat. 57, 27–34 (1994).

    CAS  PubMed  Google Scholar 

  106. 106

    Kapur, N. et al. Mammillary body damage results in memory impairment but not amnesia. Neurocase 4, 509–517 (1998). Two patients with mammillary body lesions arising from suprasellar tumours were found to have limited anterograde memory impairments but normal retrograde memory.

    Google Scholar 

  107. 107

    Kapur, N., Thompson, S., Cook, P., Lang, D. & Brice, J. Anterograde but not retrograde memory loss following combined mammillary body and medial thalamic lesions. Neuropsychologia 34, 1–8 (1996).

    CAS  PubMed  Google Scholar 

  108. 108

    Parkin, A. J. & Hunkin, N. M. Impaired temporal context memory on anterograde but not retrograde tests in the absence of frontal pathology. Cortex 29, 267–280 (1993).

    CAS  PubMed  Google Scholar 

  109. 109

    Warrington, E. K. & Weiskrantz, L. Amnesia: a disconnection syndrome? Neuropsychologia 20, 133–248 (1982).

    Google Scholar 

  110. 110

    Mair, R. G. On the role of thalamic pathology in diencephalic amnesia. Rev. Neurosci. 5, 105–140 (1994).

    CAS  PubMed  Google Scholar 

  111. 111

    Paller, K. A. et al. Functional neuroimaging of cortical dysfunction in alcoholic Korsakoff's syndrome. J. Cogn. Neurosci. 9, 277–293 (1997).

    CAS  PubMed  Google Scholar 

  112. 112

    Jenkins, T. A., Dias, R., Amin, E., Brown, M. W. & Aggleton, J. P. Fos imaging reveals that lesions of the anterior thalamic nuclei produce widespread limbic hypoactivity in rats. J. Neurosci. 22, 5230–5238 (2002).

    CAS  PubMed  Google Scholar 

  113. 113

    Savage, L. M., Chang, Q. & Gold, P. E. Diencephalic damage decreases hippocampal acetylcholine release during spontaneous alternation testing. Learn. Mem. 10, 242–246 (2003).

    PubMed  Google Scholar 

  114. 114

    Gaffan, D. in Neuropsychology of Memory (eds Squire, L. R. & Butters, N.) 336–346 (The Guildford Press, New York, 1992).

    Google Scholar 

  115. 115

    Mizumori, S. J. Y., Miya, D. Y. & Ward, K. E. Reversible inactivation of the lateral dorsal thalamus disrupts hippocampal place representation and impairs spatial learning. Brain Res. 644, 168–174 (1994).

    CAS  Google Scholar 

  116. 116

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

    Google Scholar 

  117. 117

    Burgess, N. The hippocampus, space, and viewpoints in episodic memory. Q. J. Exp. Psych. 55A, 1057–1080 (2002).

    Google Scholar 

  118. 118

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

    CAS  PubMed  Google Scholar 

  119. 119

    Kopelman, M. D. The Korsakoff syndrome. Brit. J. Psychiat. 166, 154–173 (1995).

    CAS  PubMed  Google Scholar 

  120. 120

    Korsakoff, S. S. Psychic disorder in conjunction with peripheral neuritis (1889). (Translated in 1955 by M. Victor and P. I. Yakolev in Neurology 5, 394–406).

  121. 121

    Victor, M., Adams, R. D. & Collins, G. H. The Wernicke–Korsakoff Syndrome and Related Neurologic Disorders due to Alcoholism and Malnutrition 2nd edn (F. A. Davies, Philadelphia, 1989).

    Google Scholar 

  122. 122

    Jacobson, R. R. & Lishman, W. Cortical and diencephalic lesions in Korsakoff's syndrome: a clinical and CT scan study. Psychol. Med. 20, 63–75 (1990).

    CAS  PubMed  Google Scholar 

  123. 123

    Mair, W. G. P., Warrington, E. K. & Weiskrantz, L. Memory disorder in Korsakoff's psychosis: a neuropathological and neuropsychological investigation of two cases. Brain 102, 749–783 (1979).

    CAS  PubMed  Google Scholar 

  124. 124

    Visser, P. J. et al. Brain correlates of memory dysfunction in alcoholic Korsakoff's syndrome. J. Neurol. Neurosurg. Psychiat. 67, 774–778 (1999).

    CAS  PubMed  Google Scholar 

  125. 125

    Christie, J. E. et al. Magnetic resonance imaging in pre-senile dementia of the Alzheimer type, multi-infarct dementia and Korsakoff's syndrome. Psychol. Med. 18, 319–329 (1988).

    CAS  PubMed  Google Scholar 

  126. 126

    Joyce, E. M. et al. Decreased cingulate and precuneate glucose utilization in alcoholic Korsakoff's syndrome. Psychiat. Res. 54, 225–239 (1994).

    CAS  Google Scholar 

  127. 127

    Torvik, A. Topographic distribution and severity of brain lesions in Wernicke's encephalopathy. Clin. Neuropathol. 6, 25–29 (1987).

    CAS  PubMed  Google Scholar 

  128. 128

    Tsiminakis, Y. Beitrag zur pathologie der alkoholischen erkrankungen der centralnervensystems Arbeiten aus dem Neurologischen. Institute an der Wiener Universitat 33, 24–62 (1931).

    Google Scholar 

  129. 129

    Kopelman, M. D., Ng, N. & Van Den Brouke, O. Confabulation extending across episodic, personal, and general semantic memory. Cog. Neuropsychol. 14, 683–712 (1997).

    Google Scholar 

  130. 130

    Davila, M. D., Shear, P. K., Lane, B., Sullivan, E. V. & Pfefferbaum, A. Mammillary body and cerebellar shrinkage in chronic alcoholics: an MRI and neuropsychological study. Neuropsychology 8, 433–444 (1994).

    Google Scholar 

  131. 131

    Harding, A., Halliday, G., Caine, D. & Kril, J. Degeneration of anterior thalamic nuclei differentiates alcoholics with amnesia. Brain 123, 141–154 (2000). This study used sophisticated volumetric and density measures to determine the degree of neurodegeneration in brain regions implicated in Korsakoff's syndrome. Both amnesic and non-amnesic alcoholics showed significant neuronal loss in the mammillary bodies and mediodorsal thalamic nuclei, but only neurodegeneration in the anterior thalamus was consistently associated with amnesia.

    PubMed  Google Scholar 

  132. 132

    Mayes, A. R., Meudell, R., Mann, D. & Pickering, A. Location of lesions in Korsakoff's syndrome: neuropsychological and neuropathological data on two patients. Cortex 24, 367–388 (1988).

    CAS  PubMed  Google Scholar 

  133. 133

    Malamud, N. & Skillicorn, S. A. Relationship between the Wernicke and the Korsakoff syndrome. AMA Arch. Neurol. Psychiat. 76, 585–596 (1956).

    CAS  Google Scholar 

  134. 134

    Sullivan, E. V. et al. In vivo mammillary body volume deficits in amnesic and nonamnesic alcoholics. Alcoh. Clin. Exp. Res. 23, 1629–1635 (1999).

    CAS  Google Scholar 

  135. 135

    Estruch, R. et al. Brain imaging in alcoholism. Eur. J. Neurol. 5, 119–135 (1998).

    CAS  PubMed  Google Scholar 

  136. 136

    Bassett, J. P. & Taube, J. S. Neural correlates for angular head velocity in the rat dorsal tegmental nucleus. J. Neurosci. 21, 5740–5751 (2001).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank J. Taube, N. McNaughton and N. Kapur for their invaluable help in the preparation of figures 3, 4 and 5.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Seralynne D. Vann.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

DATABASES

Omim

Korsakoff's syndrome

Glossary

EPISODIC MEMORY

The recollection of events in an autobiographical context.

THETA RHYTHM

Rhythmic neural activity with a frequency of 4–8 Hz.

MORRIS WATER MAZE

A learning task in which an animal is placed in a pool filled with opaque water and has to learn to escape to a hidden platform that is placed at a constant position. The animal must learn to use distal cues, and the spatial relationship between them and the platform. Learning in this task involves the hippocampus.

ALLOCENTRIC

Distal cues that provide geometric reference to current location.

LONG-TERM POTENTIATION

(LTP). An enduring increase in the amplitude of excitatory postsynaptic potentials as a result of high-frequency (tetanic) stimulation of afferent pathways. It is measured both as the amplitude of excitatory postsynaptic potentials and as the magnitude of the postsynaptic cell population spike. LTP is most often studied in the hippocampus and is often considered to be the cellular basis of learning and memory in vertebrates.

DIENCEPHALIC ANTEROGRADE AMNESIA

Impaired learning of new declarative information following pathology in the medial thalamic or hypothalamic regions.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Vann, S., Aggleton, J. The mammillary bodies: two memory systems in one?. Nat Rev Neurosci 5, 35–44 (2004). https://doi.org/10.1038/nrn1299

Download citation

Further reading

Search

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