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Experimental Brain Research

, Volume 76, Issue 3, pp 485–496 | Cite as

Hippocampal granule cells are necessary for normal spatial learning but not for spatially-selective pyramidal cell discharge

  • B. L. McNaughton
  • C. A. Barnes
  • J. Meltzer
  • R. J. Sutherland
Article

Summary

The effects of massive destruction of granule cells of the fascia dentata on the spatial and temporal firing characteristics of pyramidal cells in the CA1 and CA3 subfields of the hippocampus were examined in freely moving rats. Microinjections of the neurotoxin colchicine were made at a number of levels along the septo-temporal axis of the dentate gyri of both hemispheres, resulting in destruction of over 75% of the granule cells. By contrast there was relatively little damage to the pyramidal cell fields. As assessed by three different behavioral tests, the colchicine treatment resulted in severe spatial learning deficits. Single units were recorded from the CA1 and CA3 subfields using the stereotrode recording method while the animals performed a forced choice behavioral task on the radial 8-arm maze. Considering the extent of damage to the dentate gyrus, which has hitherto been considered to be the main source of afferent information to the CA fields, there was remarkably little effect on the spatial selectivity of “place cell” discharge on the maze, as compared to recordings from control animals. There was, however, a change in the temporal firing characteristics of these cells, which was manifested primarily as an increase in the likelihood of burst discharge. The main conclusion derived from these findings is that most of the spatial information exhibited by hippocampal pyramidal cells is likely to be transmitted from the cortex by routes other than the traditional “trisynaptic circuit”. These routes may include the direct projections from entorhinal layers II and III to CA3 and CA1, respectively.

Key words

Hippocampus Single units Place cells Colchicine Spatial behavior 

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References

  1. Andersen P, Bliss TVP, Skrede KK (1971) Lamellar organization of hippocampal excitatory pathways. Exp Brain Res 13:222–238Google Scholar
  2. Andersen P, Holmqvist B, Voorhoeve PE (1966) Entorhinal activation of dentate granule cells. Acta Physiol Scand 66:448–460Google Scholar
  3. Barnes CA (1979) Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat. J Comp Physiol Psychol 93:74–104Google Scholar
  4. Barnes CA, McNaughton BL, O'Keefe J (1983) Loss of place specificity in hippocampal complex-spike cells of senescent rat. Neurobiol Aging 4:113–119Google Scholar
  5. Best PJ, Ranck JB Jr (1982) The reliability of the relationship between hippocampal unit activity and sensory-behavioral events in the rat. Exp Neurol 75:652–664Google Scholar
  6. Blackstad TW (1958) On the termination of some afferents to the hippocampus and fascia dentata: an experimental study in the rat. Acta Anat 35:202–214Google Scholar
  7. Blackstad TW, Brink K, Hem J, Jeune B (1970) Distribution of hippocampal mossy fibers in the rat: an experimental study with silver impregnation methods. J Comp Neurol 138:433–450Google Scholar
  8. Cajal S Ramón y (1911) Histologie du système nerveux de l'homme et des vertébrés. A Maloine, ParisGoogle Scholar
  9. Christian EP, Deadwyler SA (1986) Behavioral functions and hippocampal cell types: evidence for two nonoverlapping populations in the rat. J Neurophysiol 55:331–348Google Scholar
  10. Claiborne BJ, Amaral DG, Cowan WM (1986) A light and electron microscopic analysis of the mossy fibers of the rat dentate gyrus. J Comp Neurol 246:435–458Google Scholar
  11. Gaarskjaer FB (1978) Organization of the mossy fiber system of the rat studied in extended hippocampi. II. Experimental analysis of fiber distribution with silver impregnation methods. J Comp Neurol 178:73–88Google Scholar
  12. Goldschmidt RB, Steward O (1980) Preferential neurotoxicity of colchicine for granule cells of the dentate gyrus of the adult rat. Proc Natl Acad Sci 77:3047–3051Google Scholar
  13. Hill AJ (1978) First occurrence of hippocampal spatial firing in a new environment. Exp Neurol 62:282–297Google Scholar
  14. Hjorth-Simonsen A (1973) Some intrinsic connections of the hippocampus in the rat: an experimental analysis. J Comp Neurol 147:163–180Google Scholar
  15. Hjorth-Simonsen A, Jeune B (1972) Origin and termination of the hippocampal perforant path in the rat, studied with silver impregnation. J Comp Neurol 144:215–232Google Scholar
  16. Hjorth-Simonsen A, Laurberg S (1977) Commissural connections of the dentate area in the rat. J Comp Neurol 174:591–606Google Scholar
  17. Ishizuka N, Kremieniewska K, Amaral DG (1986) Organization of pyramidal cell axonal collaterals in field CA3 of the rat hippocampus. Soc Neurosci Abstr 12:1254Google Scholar
  18. Jarrard LE (1978) Selective lesions: Differential effects on performance with preoperative versus postoperative training. J Comp Physiol Psychol 92:119–127Google Scholar
  19. Jarrard LE (1983) Selective hippocampal lesions and behavior: effects of kainic acid lesions on performance of place and cue tasks. Behav Neurosci 97:873–889Google Scholar
  20. Jarrard LE (1986) Selective hippocampal lesions and behavior: implications for current research and theorizing. In: Isaacson RL, Pribram KH (eds) The hippocampus, Vol 4. Plenum, New York, pp 93–127Google Scholar
  21. Jarrard LE, Okaichi H, Goldschmidt R, Steward O (1984) On the role of the hippocampal connections in the performance of place and cue tasks: comparisons with damage to the hippocampus. Behav Neurosci 98:946–954Google Scholar
  22. Jones Leonard B, McNaughton BL, Barnes CA (1985) Long-term studies of place field interrelationships in dentate gyrus neurons. Soc Neurosci Abstr 11:1108Google Scholar
  23. Laurberg S (1979) Commissural and intrinsic connections of the hippocampus. J Comp Neurol 184:685–708Google Scholar
  24. Laurberg S, Sørensen KE (1981) Associational and commissural collaterals of neurons in the hippocampal formation (hilus fasciae dentate and subfield CA3). Brain Res 212:297–300Google Scholar
  25. Lorente de Nó R (1934) Studies on the structure of the cerebral cortex. II. Continuation of the study of ammonic system. J Psychol Neurol (Lpz) 46:113–177Google Scholar
  26. Marr D (1971) Simple memory: a theory of archicortex. Philos Trans R Soc (Biol) 262:23–80Google Scholar
  27. McNaughton BL, Morris RGM (1988) Hippocampal synaptic enhancement and information storage within a distributed memory system. TINS 10:408–415Google Scholar
  28. McNaughton BL, Barnes CA, O'Keefe J (1983) The contributions of position, direction, and velocity to single unit activity in the hippocampus of freely-moving rats. Exp Brain Res 52:41–49Google Scholar
  29. McNaughton BL, O'Keefe J, Barnes CA (1983) The stereotrode: a new technique for simultaneous isolation of several single units in the central nervous system from multiple unit records. J Neurosci Methods 8:391–397Google Scholar
  30. McNaughton BL, Meltzer J, Sutherland RJ, Barnes CA (1988) Beyond the trisynaptic loop: evidence for distributed spatial representations in hippocampal circuits. Soc Neurosci Abstr 14:395Google Scholar
  31. Miller VM, Best PJ (1980) Spatial correlates of hippocampal unit activity are altered by lesions of the fornix and entorhinal cortex. Brain Res 194:311–323Google Scholar
  32. Mizumori SJY, McNaughton BL, Barnes CA, Fox K (1987) Reversible inactivation of hippocampal afferents selectively reduces the spontaneous discharge rate of dentate units. Soc Neurosci Abstr 13:1102Google Scholar
  33. Mizumori SJY, McNaughton BL, Barnes CA (1989) A comparison of supramammillary and medial septal influences on hippocampal field potential and single unit activity. J Neurophysiol 61:15–31Google Scholar
  34. Molino A, McIntyre DL (1972) Another inexpensive headplug for the electrical recording and/or stimulation of rats. Physiol Behav 9:273–275Google Scholar
  35. Morris RGM (1981) Spatial localization does not require the presence of local cues. Learn Motiv 12:239–260Google Scholar
  36. Morris RGM, Garrud P, Rawlins JNP, O'Keefe J (1982) Place navigation impaired in rats with hippocampal lesions. Nature 297:681–683Google Scholar
  37. Muller RU, Kubie JL (1987) The effects of changes in the environment on the spatial firing of hippocampal complex spike cells. J Neurosci 7:1951–1968Google Scholar
  38. Muller RU, Kubie JL, Ranck JB Jr (1987) Spatial firing patterns of hippocampal complex-spike cells in a fixed environment. J Neurosci 7:1935–1950Google Scholar
  39. Nadel L, McDonald L (1980) Hippocampus: cognitive map or working memory? Behav Neurol Biol 29:405–409Google Scholar
  40. Nanry KP, Mundy WR, Tilson HA (1988) Intradentate colchicine-induced impairment of reference memory: spatial vs nonspatial. Soc Neurosci Abstr 14:235Google Scholar
  41. O'Keefe J (1976) Place units in the hippocampus of the freely moving rat. Exp Neurol 51:78–109Google Scholar
  42. O'Keefe J (1983) Spatial memory within and without the hippocampal system. In: Seifert W (ed) Neurobiology of the hippocampus. Academic Press, New York, pp 375–403Google Scholar
  43. O'Keefe J, Conway DH (1978) Hippocampal place units in the freely moving rat: why they fire where they fire. Exp Brain Res 31:573–590Google Scholar
  44. O'Keefe J, Dostrovsky J (1971) The hippocampus as a spatial map: preliminary evidence from unit activity in the freelymoving rat. Brain Res 34:171–175Google Scholar
  45. O'Keefe J, Nadel L (1978) The hippocampus as a cognitive map. Clarendon Press, LondonGoogle Scholar
  46. O'Keefe J, Speakman A (1987) Single unit activity in the rat hippocampus during a spatial memory task. Exp Brain Res 68:1–27Google Scholar
  47. O'Keefe J, Nadel L, Keightly S, Kill D (1975) Fornix lesions selectively abolish place learning in the rat. Exp Neurol 48:152–166Google Scholar
  48. Olton DS, Branch M, Best PJ (1978) Spatial correlates of hippocampal unit activity. Exp Neurol 58:387–409Google Scholar
  49. Olton DS, Samuelson RJ (1976) Remembrance of places past: spatial memory in rats. J Exp Psychol [Anim Behav] 2:97–116Google Scholar
  50. Olton DS, Walker JA, Gage FH (1978) Hippocampal connections and spatial discrimination. Brain Res 139:295–308Google Scholar
  51. Ranck JB Jr (1973) Studies on single neurons in dorsal hippocampal formation and septum in unrestrained rats. I. Behavioral correlates and firing repertoires. Exp Neurol 41:461–535Google Scholar
  52. Schaffer K (1892) Beitrag zur Histologie der Ammonhorn-Formation. Arch Mikr Anat 39:611–632Google Scholar
  53. Steward O, Scoville SA (1976) Cells of origin of entorhinal cortical afferents to the hippocampus and fascia dentata in the rat. J Comp Neurol 169:347–370Google Scholar
  54. Sutherland RJ (1985) The navigating hippocampus: an individual medley of space, memory and movement. In: Buzsaki G, Vanderwolf CH (eds) Electrical activity of the archicortex. Akademai Kiado, Budapest, pp 255–279Google Scholar
  55. Sutherland RJ, Rudy JW (1989) Configural association theory: the role of the hippocampal formation in learning memory and amnesia. Psychobiology (in press)Google Scholar
  56. Sutherland RJ, Kolb B, Wishaw IQ (1982) Spatial mapping: definitive disruption by hippocampal or medial frontal cortical damage in the rat. Neurosci Lett 31:271–276Google Scholar
  57. Sutherland RJ, Wishaw IQ, Kolb B (1983) A behavioral analysis of spatial localization following electrolytic, kainate-, or colchicine-induced damage to the hippocampal formation in the rat. Behav Brain Res 7:133–153Google Scholar
  58. Swanson LW, Sawchenko PE, Cowan WM (1981) Evidence for collateral projections by neurons in Ammon's horn, the dentate gyrus, and the subiculum: a multiple retrograde labelling study in the rat. J Neurosci 1:548–559Google Scholar
  59. Swanson LW, Wyss JM, Cowan WM (1978) An autoradiographic study of the organization of intrahippocampal association pathways in the rat. J Comp Neurol 181:681–718Google Scholar
  60. Wishaw IQ (1987) Hippocampal, granule cell and CA3-4 lesions impair formation of a place learning-set in the rat and induce reflex epilepsy. Behav Brain Res 24:59–72Google Scholar
  61. Witter MP, Griffioen AW, Jorritsma-Byham B, Krijnen JLM (1988) Entorhinal projections to the hippocampal CA1 region in the rat: an underestimated pathway. Neurosci Lett 85:193–198Google Scholar
  62. Yeckel MF, Barrionuevo G, Berger TW (1988) In vivo electrophysiological evidence for monosynaptic input from the entorhinal cortex to pyramidal cell regions of the hippocampus. Soc Neurosci Abstr 14:246Google Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • B. L. McNaughton
    • 1
  • C. A. Barnes
    • 1
  • J. Meltzer
    • 1
  • R. J. Sutherland
    • 2
  1. 1.Department of PsychologyUniversity of ColoradoBoulderUSA
  2. 2.Department of PsychologyUniversity of LethbridgeLethbridgeCanada

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