Spatial and Nonspatial Representations in the Lateral Entorhinal Cortex

Chapter

Abstract

The hippocampus is thought to function as a “cognitive map,” which stores nonspatial information such as items and events in a spatial framework. In order to understand the computations involved in creating such conjunctive nonspatial + spatial representations, it is essential to understand the function of hippocampal inputs. Medial entorhinal cortex (MEC) is known to convey spatial information to the hippocampus. In this chapter, we discuss recent evidence showing that lateral entorhinal cortex (LEC) conveys both spatial and nonspatial information to the hippocampus, in the presence of objects. Perirhinal cortex (PRC), a major cortical input to LEC, encodes nonspatial, object-related information, but does not encode spatial information in the presence of objects. Thus, the landmark-derived spatial information arises de novo in LEC. The classical dual-pathway model, in which LEC encodes nonspatial information while MEC encodes spatial information, cannot account for LEC spatial representation in the presence of objects. We propose that the functional difference between LEC and MEC is better understood in terms of the different inputs they use to create their representations: LEC generates spatial as well as nonspatial representations by processing external sensory inputs in contrast to MEC, which generates spatial representations by processing internally based path integration information.

References

  1. Aggleton JP, Brown MW (1999) Episodic memory, amnesia, and the hippocampal-anterior thalamic axis. Behav Brain Sci 22:425–444PubMedGoogle Scholar
  2. Alonso A, Garcia-Austt E (1987a) Neuronal sources of theta rhythm in the entorhinal cortex of the rat. I. Laminar distribution of theta field potentials. Exp Brain Res 67:493–501PubMedGoogle Scholar
  3. Alonso A, Garcia-Austt E (1987b) Neuronal sources of theta rhythm in the entorhinal cortex of the rat. II. Phase relations between unit discharges and theta field potentials. Exp Brain Res 67:502–509PubMedGoogle Scholar
  4. Bannerman DM, Yee BK, Lemaire M, Wilbrecht L, Jarrard L, Iversen SD, Rawlins JN, Good MA (2001) The role of the entorhinal cortex in two forms of spatial learning and memory. Exp Brain Res 141(3):281–303PubMedGoogle Scholar
  5. Bi GQ, Poo MM (1998) Synaptic modifications in cultured hippocampal neurons: dependence on spike timing, synaptic strength, and postsynaptic cell type. J Neurosci 18:10464–10472PubMedGoogle Scholar
  6. Blair HT, Fanselow MS (2014) Fear and memory: a view of the hippocampus through the lens of the amygdala. In: Derdikman D, Knierim JJ (eds) Space, time and memory in the hippocampal formation. Springer, HeidelbergGoogle Scholar
  7. Bramham CR, Errington ML, Bliss TV (1988) Naloxone blocks the induction of long-term potentiation in the lateral but not in the medial perforant pathway in the anesthetized rat. Brain Res 449:352–356PubMedGoogle Scholar
  8. Bramham CR, Milgram NW, Srebro B (1991a) Activation of AP5-sensitive NMDA receptors is not required to induce LTP of synaptic transmission in the lateral perforant path. Eur J Neurosci 3:1300–1308PubMedGoogle Scholar
  9. Bramham CR, Milgram NW, Srebro B (1991b) Delta opioid receptor activation is required to induce LTP of synaptic transmission in the lateral perforant path in vivo. Brain Res 567:42–50PubMedGoogle Scholar
  10. Brun VH, Solstad T, Kjelstrup KB, Fyhn M, Witter MP, Moser EI, Moser MB (2008) Progressive increase in grid scale from dorsal to ventral medial entorhinal cortex. Hippocampus 18:1200–1212PubMedGoogle Scholar
  11. Burgess N, Barry C, O’Keefe J (2007) An oscillatory interference model of grid cell firing. Hippocampus 17:801–812PubMedCentralPubMedGoogle Scholar
  12. Burke SN, Maurer AP, Hartzell AL, Nematollahi S, Uprety A, Wallace JL, Barnes CA (2012) Representation of three-dimensional objects by the rat perirhinal cortex. Hippocampus 22:2032–2044PubMedCentralPubMedGoogle Scholar
  13. Burwell RD (2000) The parahippocampal region: corticocortical connectivity. Ann N Y Acad Sci 911:25–42PubMedGoogle Scholar
  14. Burwell RD, Amaral DG (1998) Cortical afferents of the perirhinal, postrhinal, and entorhinal cortices of the rat. J Comp Neurol 398:179–205PubMedGoogle Scholar
  15. Buzsaki G (2002) Theta oscillations in the hippocampus. Neuron 33:325–340PubMedGoogle Scholar
  16. Canto CB, Wouterlood FG, Witter MP (2008) What does the anatomical organization of the entorhinal cortex tell us? Neural Plast 2008:381243. doi:10.1155/2008/381243 PubMedCentralPubMedGoogle Scholar
  17. Clayton NS, Dickinson A (1998) Episodic-like memory during cache recovery by scrub jays. Nature 395:272–274PubMedGoogle Scholar
  18. Collett TS, Cartwright BA, Smith BA (1986) Landmark learning and visuo-spatial memories in gerbils. J Comp Physiol A 158:835–851PubMedGoogle Scholar
  19. de Curtis M, Pare D (2004) The rhinal cortices: a wall of inhibition between the neocortex and the hippocampus. Prog Neurobiol 74:101–110PubMedGoogle Scholar
  20. Derdikman D, Moser EI (2014) Spatial maps in the entorhinal cortex and adjacent structures. In: Derdikman D, Knierim JJ (eds) Space, time and memory in the hippocampal formation. Springer, HeidelbergGoogle Scholar
  21. Deshmukh SS, Knierim JJ (2011) Representation of non-spatial and spatial information in the lateral entorhinal cortex. Front Behav Neurosci 5:69. doi:10.3389/fnbeh.2011.00069 PubMedCentralPubMedGoogle Scholar
  22. Deshmukh SS, Knierim JJ (2012) Hippocampus. Wiley Interdiscip Rev Cogn Sci 3:231–251Google Scholar
  23. Deshmukh SS, Knierim JJ (2013) Influence of local objects on hippocampal representations: landmark vectors and memory. Hippocampus 23:253–267PubMedGoogle Scholar
  24. Deshmukh SS, Yoganarasimha D, Voicu H, Knierim JJ (2010) Theta modulation in the medial and the lateral entorhinal cortices. J Neurophysiol 104:994–1006PubMedCentralPubMedGoogle Scholar
  25. Deshmukh SS, Johnson JL, Knierim JJ (2012) Perirhinal cortex represents nonspatial, but not spatial, information in rats foraging in the presence of objects: comparison with lateral entorhinal cortex. Hippocampus 22:2045–2058PubMedGoogle Scholar
  26. Do VH, Martinez CO, Martinez JL, Derrick BE (2002) Long-term potentiation in direct perforant path projections to the hippocampal CA3 region in vivo. J Neurophysiol 87:669–678PubMedGoogle Scholar
  27. Dolorfo CL, Amaral DG (1998a) Entorhinal cortex of the rat: organization of intrinsic connections. J Comp Neurol 398:49–82PubMedGoogle Scholar
  28. Dolorfo CL, Amaral DG (1998b) Entorhinal cortex of the rat: topographic organization of the cells of origin of the perforant path projection to the dentate gyrus. J Comp Neurol 398:25–48PubMedGoogle Scholar
  29. Eichenbaum H, Fortin NJ (2005) Bridging the gap between brain and behavior: cognitive and neural mechanisms of episodic memory. J Exp Anal Behav 84:619–629PubMedCentralPubMedGoogle Scholar
  30. Eichenbaum H, Yonelinas AP, Ranganath C (2007) The medial temporal lobe and recognition memory. Annu Rev Neurosci 30:123–152PubMedCentralPubMedGoogle Scholar
  31. Fanselow MS, Dong HW (2010) Are the dorsal and ventral hippocampus functionally distinct structures? Neuron 65:7–19PubMedCentralPubMedGoogle Scholar
  32. Fox SE, Ranck JB (1981) Electrophysiological characteristics of hippocampal complex-spike cells and theta cells. Exp Brain Res 41:399–410PubMedGoogle Scholar
  33. Frank LM, Brown EN, Wilson MA (2001) A comparison of the firing properties of putative excitatory and inhibitory neurons from CA1 and the entorhinal cortex. J Neurophysiol 86:2029–2040PubMedGoogle Scholar
  34. Fredens K, Stengaard-Pedersen K, Larsson LI (1984) Localization of enkephalin and cholecystokinin immunoreactivities in the perforant path terminal fields of the rat hippocampal formation. Brain Res 304:255–263PubMedGoogle Scholar
  35. Fuhs MC, Touretzky DS (2006) A spin glass model of path integration in rat medial entorhinal cortex. J Neurosci 26:4266–4276PubMedGoogle Scholar
  36. Furtak SC, Ahmed OJ, Burwell RD (2012) Single neuron activity and theta modulation in postrhinal cortex during visual object discrimination. Neuron 76:976–988PubMedCentralPubMedGoogle Scholar
  37. Gall C, Brecha N, Karten HJ, Chang KJ (1981) Localization of enkephalin-like immunoreactivity to identified axonal and neuronal populations of the rat hippocampus. J Comp Neurol 198:335–350PubMedGoogle Scholar
  38. Glasier MM, Sutton RL, Stein DG (1995) Effects of unilateral entorhinal cortex lesion and ganglioside GM1 treatment on performance in a novel water maze task. Neurobiol Learn Mem 64:203–214PubMedGoogle Scholar
  39. Glasier MM, Janis LS, Roof RL, Stein DG (1999) Effects of unilateral entorhinal cortex lesion on retention of water maze performance. Neurobiol Learn Mem 71:19–33PubMedGoogle Scholar
  40. Good M, Honey RC (1997) Dissociable effects of selective lesions to hippocampal subsystems on exploratory behavior, contextual learning, and spatial learning. Behav Neurosci 111:487–493PubMedGoogle Scholar
  41. Hafting T, Fyhn M, Molden S, Moser MB, Moser EI (2005) Microstructure of a spatial map in the entorhinal cortex. Nature 436:801–806PubMedGoogle Scholar
  42. Hafting T, Fyhn M, Bonnevie T, Moser MB, Moser EI (2008) Hippocampus-independent phase precession in entorhinal grid cells. Nature 453:1248–1252PubMedGoogle Scholar
  43. Hargreaves EL, Rao G, Lee I, Knierim JJ (2005) Major dissociation between medial and lateral entorhinal input to dorsal hippocampus. Science 308:1792–1794PubMedGoogle Scholar
  44. Hasselmo ME, Giocomo LM, Zilli EA (2007) Grid cell firing may arise from interference of theta frequency membrane potential oscillations in single neurons. Hippocampus 17:1252–1271PubMedCentralPubMedGoogle Scholar
  45. Henriksen EJ, Colgin LL, Barnes CA, Witter MP, Moser MB, Moser EI (2010) Spatial representation along the proximodistal axis of CA1. Neuron 68:127–137PubMedCentralPubMedGoogle Scholar
  46. Ho JW, Burwell RD (2014) Perirhinal and postrhinal functional inputs to the hippocampus. In: Derdikman D, Knierim JJ (eds) Space, time and memory in the hippocampal formation. Springer, HeidelbergGoogle Scholar
  47. Hunsaker MR, Chen V, Tran GT, Kesner RP (2013) The medial and lateral entorhinal cortex both contribute to contextual and item recognition memory: a test of the binding of items and context model. Hippocampus 23:380–391PubMedGoogle Scholar
  48. Kajiwara R, Takashima I, Mimura Y, Witter MP, Iijima T (2003) Amygdala input promotes spread of excitatory neural activity from perirhinal cortex to the entorhinal-hippocampal circuit. J Neurophysiol 89:2176–2184PubMedGoogle Scholar
  49. Kerr KM, Agster KL, Furtak SC, Burwell RD (2007) Functional neuroanatomy of the parahippocampal region: the lateral and medial entorhinal areas. Hippocampus 17:697–708PubMedGoogle Scholar
  50. Knierim JJ (2006) Neural representations of location outside the hippocampus. Learn Mem 13:405–415PubMedGoogle Scholar
  51. Knierim JJ, Lee I, Hargreaves EL (2006) Hippocampal place cells: parallel input streams, subregional processing, and implications for episodic memory. Hippocampus 16:755–764PubMedGoogle Scholar
  52. Komorowski RW, Manns JR, Eichenbaum H (2009) Robust conjunctive item-place coding by hippocampal neurons parallels learning what happens where. J Neurosci 29:9918–9929PubMedCentralPubMedGoogle Scholar
  53. Las L, Ulanovsky N (2014) Hippocampal neurophysiology across species. In: Derdikman D, Knierim JJ (eds) Space, time and memory in the hippocampal formation. Springer, HeidelbergGoogle Scholar
  54. Lenck-Santini PP, Rivard B, Muller RU, Poucet B (2005) Study of CA1 place cell activity and exploratory behavior following spatial and nonspatial changes in the environment. Hippocampus 15:356–369PubMedGoogle Scholar
  55. Lever C, Kaplan R, Burgess N (2014) The function of oscillations in the hippocampal formation. In: Derdikman D, Knierim JJ (eds) Space, time and memory in the hippocampal formation. Springer, HeidelbergGoogle Scholar
  56. Lisman JE (2007) Role of the dual entorhinal inputs to hippocampus: a hypothesis based on cue/action (non-self/self) couplets. Prog Brain Res 163:615–625PubMedGoogle Scholar
  57. Lu L, Leutgeb JK, Tsao A, Henriksen EJ, Leutgeb S, Barnes CA, Witter MP, Moser MB, Moser EI (2013) Impaired hippocampal rate coding after lesions of the lateral entorhinal cortex. Nat Neurosci 16:1085–1093PubMedGoogle Scholar
  58. Manns JR, Eichenbaum H (2006) Evolution of declarative memory. Hippocampus 16:795–808PubMedGoogle Scholar
  59. Manns JR, Eichenbaum H (2009) A cognitive map for object memory in the hippocampus. Learn Mem 16:616–624PubMedCentralPubMedGoogle Scholar
  60. Martinez CO, Do VH, Derrick BE (2011) Endogenous opioid peptides contribute to associative LTP in the hippocampal CA3 region. Neurobiol Learn Mem 96:207–217PubMedCentralPubMedGoogle Scholar
  61. McNaughton BL, Knierim JJ, Wilson MA (1995) Vector encoding and the vestibular foundations of spatial cognition: neurophysiological and computational mechanisms. In: Gazzaniga MS (ed) The cognitive neurosciences. MIT Press, Cambridge, MA, pp 585–595Google Scholar
  62. McNaughton BL, Battaglia FP, Jensen O, Moser EI, Moser MB (2006) Path integration and the neural basis of the ‘cognitive map’. Nat Rev Neurosci 7:663–678PubMedGoogle Scholar
  63. Miller VM, Best PJ (1980) Spatial correlates of hippocampal unit activity are altered by lesions of the fornix and entorhinal cortex. Brain Res 194:311–323PubMedGoogle Scholar
  64. Mitchell SJ, Ranck JB (1980) Generation of theta rhythm in medial entorhinal cortex of freely moving rats. Brain Res 189:49–66PubMedGoogle Scholar
  65. Morris RG, Frey U (1997) Hippocampal synaptic plasticity: role in spatial learning or the automatic recording of attended experience? Philos Trans R Soc Lond B Biol Sci 352:1489–1503PubMedCentralPubMedGoogle Scholar
  66. Moser MB, Moser EI (1998) Functional differentiation in the hippocampus. Hippocampus 8:608–619PubMedGoogle Scholar
  67. Murray EA, Bussey TJ, Saksida LM (2007) Visual perception and memory: a new view of medial temporal lobe function in primates and rodents. Annu Rev Neurosci 30:99–122PubMedGoogle Scholar
  68. Naber PA, Lopes da Silva FH, Witter MP (2001) Reciprocal connections between the entorhinal cortex and hippocampal fields CA1 and the subiculum are in register with the projections from CA1 to the subiculum. Hippocampus 11:99–104PubMedGoogle Scholar
  69. Nakamura NH, Flashbeck V, Maingret N, Kitsukawa T, Sauvage MM (2013) Proximodistal segregation of nonspatial information in CA3: preferential recruitment of a proximal CA3-distal CA1 network in nonspatial recognition memory. J Neurosci 33:11506–11514PubMedGoogle Scholar
  70. Navratilova Z, McNaughton BL (2014) Models of path integration in the hippocampal complex. In: Derdikman D, Knierim JJ (eds) Space, time and memory in the hippocampal formation. Springer, HeidelbergGoogle Scholar
  71. Neunuebel JP, Yoganarasimha D, Rao G, Knierim JJ (2013) Conflicts between local and global spatial frameworks dissociate neural representations of the lateral and medial entorhinal cortex. J Neurosci 33:9246–9258PubMedCentralPubMedGoogle Scholar
  72. O’Keefe J (1976) Place units in the hippocampus of the freely moving rat. Exp Neurol 51:78–109PubMedGoogle Scholar
  73. O’Keefe J, Burgess N (2005) Dual phase and rate coding in hippocampal place cells: theoretical significance and relationship to entorhinal grid cells. Hippocampus 15:853–866PubMedCentralPubMedGoogle Scholar
  74. O’Keefe J, Nadel L (1978) The hippocampus as a cognitive map. Clarendon, OxfordGoogle Scholar
  75. O’Keefe J, Recce ML (1993) Phase relationship between hippocampal place units and the EEG theta rhythm. Hippocampus 3:317–330PubMedGoogle Scholar
  76. Oswald CJ, Bannerman DM, Yee BK, Rawlins JN, Honey RC, Good M (2003) Entorhinal cortex lesions disrupt the transition between the use of intra- and extramaze cues for navigation in the water maze. Behav Neurosci 117:588–595PubMedGoogle Scholar
  77. Ranck JB (1973) Studies on single neurons in dorsal hippocampal formation and septum in unrestrained rats. I. Behavioral correlates and firing repertoires. Exp Neurol 41:461–531PubMedGoogle Scholar
  78. Scoville WB, Milner B (1957) Loss of recent memory after bilateral hippocampal lesions. J Neurol Neurosurg Psychiatry 20:11–21PubMedCentralPubMedGoogle Scholar
  79. Skaggs WE, McNaughton BL, Wilson MA, Barnes CA (1996) Theta phase precession in hippocampal neuronal populations and the compression of temporal sequences. Hippocampus 6:149–172PubMedGoogle Scholar
  80. Squire LR, Stark CE, Clark RE (2004) The medial temporal lobe. Annu Rev Neurosci 27:279–306PubMedGoogle Scholar
  81. Steward O, Scoville SA (1976) Cells of origin of entorhinal cortical afferents to the hippocampus and fascia dentata of the rat. J Comp Neurol 169:347–370PubMedGoogle Scholar
  82. Stewart M, Quirk GJ, Barry M, Fox SE (1992) Firing relations of medial entorhinal neurons to the hippocampal theta rhythm in urethane anesthetized and walking rats. Exp Brain Res 90:21–28PubMedGoogle Scholar
  83. Suzuki WA, Amaral DG (1994a) Perirhinal and parahippocampal cortices of the macaque monkey: cortical afferents. J Comp Neurol 350:497–533PubMedGoogle Scholar
  84. Suzuki WA, Amaral DG (1994b) Topographic organization of the reciprocal connections between the monkey entorhinal cortex and the perirhinal and parahippocampal cortices. J Neurosci 14:1856–1877PubMedGoogle Scholar
  85. Suzuki WA, Miller EK, Desimone R (1997) Object and place memory in the macaque entorhinal cortex. J Neurophysiol 78:1062–1081PubMedGoogle Scholar
  86. Taube JS, Muller RU, Ranck JB (1990) Head-direction cells recorded from the postsubiculum in freely moving rats. I. Description and quantitative analysis. J Neurosci 10:420–435PubMedGoogle Scholar
  87. Tsao A, Moser MB, Moser EI (2013) Traces of experience in the lateral entorhinal cortex. Curr Biol 23:399–405PubMedGoogle Scholar
  88. Ungerleider LG, Mishkin M (1982) Two cortical visual systems. In: Ingle DJ, Goodale MA, Mansfield RJW (eds) Analysis of visual behavior. MIT Press, Cambridge, MA, pp 549–586Google Scholar
  89. Van Cauter T, Poucet B, Save E (2008) Unstable CA1 place cell representation in rats with entorhinal cortex lesions. Eur J Neurosci 27:1933–1946PubMedGoogle Scholar
  90. Van Cauter T, Camon J, Alvernhe A, Elduayen C, Sargolini F, Save E (2013) Distinct roles of medial and lateral entorhinal cortex in spatial cognition. Cereb Cortex 23:451–459PubMedGoogle Scholar
  91. Vargha-Khadem F, Gadian DG, Watkins KE, Connelly A, Van Paesschen W, Mishkin M (1997) Differential effects of early hippocampal pathology on episodic and semantic memory. Science 277:376–380PubMedGoogle Scholar
  92. Wan H, Aggleton JP, Brown MW (1999) Different contributions of the hippocampus and perirhinal cortex to recognition memory. J Neurosci 19:1142–1148PubMedGoogle Scholar
  93. Weible AP, Rowland DC, Pang R, Kentros C (2009) Neural correlates of novel object and novel location recognition behavior in the mouse anterior cingulate cortex. J Neurophysiol 102:2055–2068PubMedGoogle Scholar
  94. Weible AP, Rowland DC, Monaghan CK, Wolfgang NT, Kentros CG (2012) Neural correlates of long-term object memory in the mouse anterior cingulate cortex. J Neurosci 32:5598–5608PubMedGoogle Scholar
  95. Wilson DI, Langston RF, Schlesiger MI, Wagner M, Watanabe S, Ainge JA (2013) Lateral entorhinal cortex is critical for novel object-context recognition. Hippocampus 23:352–366PubMedCentralPubMedGoogle Scholar
  96. Winter SS, Taube JS (2014) Head direction cells: from generation to integration. In: Derdikman D, Knierim JJ (eds) Space, time and memory in the hippocampal formation. Springer, HeidelbergGoogle Scholar
  97. Witter MP, Amaral DG (2004) Hippocampal formation. In: Paxinos G (ed) The rat nervous system, 3rd edn. Elsevier, Amsterdam, pp 635–704Google Scholar
  98. Witter MP, Groenewegen HJ, Lopes da Silva FH, Lohman AH (1989) Functional organization of the extrinsic and intrinsic circuitry of the parahippocampal region. Prog Neurobiol 33:161–253PubMedGoogle Scholar
  99. Wood ER, Dudchenko PA, Eichenbaum H (1999) The global record of memory in hippocampal neuronal activity. Nature 397:613–616PubMedGoogle Scholar
  100. Yoganarasimha D, Yu X, Knierim JJ (2006) Head direction cell representations maintain internal coherence during conflicting proximal and distal cue rotations: comparison with hippocampal place cells. J Neurosci 26:622–631PubMedCentralPubMedGoogle Scholar
  101. Yoganarasimha D, Rao G, Knierim JJ (2011) Lateral entorhinal neurons are not spatially selective in cue-rich environments. Hippocampus 21:1363–1374PubMedCentralPubMedGoogle Scholar
  102. Young BJ, Otto T, Fox GD, Eichenbaum H (1997) Memory representation within the parahippocampal region. J Neurosci 17:5183–5195PubMedGoogle Scholar
  103. Zhu XO, Brown MW, Aggleton JP (1995a) Neuronal signalling of information important to visual recognition memory in rat rhinal and neighbouring cortices. Eur J Neurosci 7:753–765PubMedGoogle Scholar
  104. Zhu XO, Brown MW, McCabe BJ, Aggleton JP (1995b) Effects of the novelty or familiarity of visual stimuli on the expression of the immediate early gene c-fos in rat brain. Neuroscience 69:821–829PubMedGoogle Scholar

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© Springer-Verlag Wien 2014

Authors and Affiliations

  1. 1.Krieger Mind/Brain InstituteJohns Hopkins UniversityBaltimoreUSA

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