Article | Published:

Impaired hippocampal rate coding after lesions of the lateral entorhinal cortex

Nature Neuroscience volume 16, pages 10851093 (2013) | Download Citation

Subjects

Abstract

In the hippocampus, spatial and non-spatial parameters may be represented by a dual coding scheme, in which coordinates in space are expressed by the collective firing locations of place cells and the diversity of experience at these locations is encoded by orthogonal variations in firing rates. Although the spatial signal may reflect input from medial entorhinal cortex, the sources of the variations in firing rate have not been identified. We found that rate variations in rat CA3 place cells depended on inputs from the lateral entorhinal cortex (LEC). Hippocampal rate remapping, induced by changing the shape or the color configuration of the environment, was impaired by lesions in those parts of the ipsilateral LEC that provided the densest input to the hippocampal recording position. Rate remapping was not observed in LEC itself. The findings suggest that LEC inputs are important for efficient rate coding in the hippocampus.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    & The Hippocampus as a Cognitive Map (Oxford University Press, New York, 1978).

  2. 2.

    , & Place cells, grid cells, and the brain's spatial representation system. Annu. Rev. Neurosci. 31, 69–89 (2008).

  3. 3.

    & The effects of changes in the environment on the spatial firing of hippocampal complex-spike cells. J. Neurosci. 7, 1951–1968 (1987).

  4. 4.

    & Dynamics of the hippocampal ensemble code for space. Science 261, 1055–1058 (1993).

  5. 5.

    , , , & Distinct ensemble codes in hippocampal areas CA3 and CA1. Science 305, 1295–1298 (2004).

  6. 6.

    , & Correlates of hippocampal complex-spike activity in rats performing a nonspatial radial maze task. J. Neurosci. 14, 6553–6563 (1994).

  7. 7.

    , & The global record of memory in hippocampal neuronal activity. Nature 397, 613–616 (1999).

  8. 8.

    , & Robust conjunctive item-place coding by hippocampal neurons parallels learning what happens where. J. Neurosci. 29, 9918–9929 (2009).

  9. 9.

    , , & Internally generated cell assembly sequences in the rat hippocampus. Science 321, 1322–1327 (2008).

  10. 10.

    , , & Hippocampal 'time cells' bridge the gap in memory for discontiguous events. Neuron 71, 737–749 (2011).

  11. 11.

    et al. Interactions between location and task affect the spatial and directional firing of hippocampal neurons. J. Neurosci. 15, 7079–7094 (1995).

  12. 12.

    , , , & Putting fear in its place; remapping of hippocampal place cells during fear conditioning. J. Neurosci. 24, 7015–7023 (2004).

  13. 13.

    et al. Independent codes for spatial and episodic memory in the hippocampus. Science 309, 619–623 (2005).

  14. 14.

    , , , & Spatial representation in the entorhinal cortex. Science 305, 1258–1264 (2004).

  15. 15.

    , , & Major dissociation between medial and lateral entorhinal input to the dorsal hippocampus. Science 308, 1792–1794 (2005).

  16. 16.

    , , , & Microstructure of a spatial map in the entorhinal cortex. Nature 436, 801–806 (2005).

  17. 17.

    , , , & Hippocampal remapping and grid realignment in entorhinal cortex. Nature 446, 190–194 (2007).

  18. 18.

    et al. The entorhinal grid map is discretized. Nature 492, 72–78 (2012).

  19. 19.

    , & Object and place memory in the macaque entorhinal cortex. J. Neurophysiol. 78, 1062–1081 (1997).

  20. 20.

    , , & Memory representation within the parahippocampal region. J. Neurosci. 17, 5183–5195 (1997).

  21. 21.

    & Representation of non-spatial and spatial information in the lateral entorhinal cortex. Front. Behav. Neurosci 5, 69 (2011).

  22. 22.

    , & Traces of experience in the lateral entorhinal cortex. Curr. Biol. 23, 399–405 (2013).

  23. 23.

    et al. Representation of three-dimensional objects by the rat perirhinal cortex. Hippocampus 22, 2032–2044 (2012).

  24. 24.

    , & Perirhinal cortex represents nonspatial, but not spatial, information in rats foraging in the presence of objects: comparison with lateral entorhinal cortex. Hippocampus 22, 2045–2058 (2012).

  25. 25.

    , , & Functional organization of the extrinsic and intrinsic circuitry of the parahippocampal region. Prog. Neurobiol. 33, 161–253 (1989).

  26. 26.

    & 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, 25–48 (1998).

  27. 27.

    & Hippocampal formation. in The Rat Nervous System 3rd edn. (ed. Paxinos, G.) 635–704 (Elsevier Academic Press, 2004).

  28. 28.

    et al. Progressive transformation of hippocampal neuronal representations in 'morphed' environments. Neuron 48, 345–358 (2005).

  29. 29.

    , & Topographical relationship between the entorhinal cortex and the septotemporal axis of the dentate gyrus in rats. II. Cells projecting from lateral entorhinal subdivisions. J. Comp. Neurol. 270, 506–516 (1988).

  30. 30.

    , , , & Attractor dynamics in the hippocampal representation of the local environment. Science 308, 873–876 (2005).

  31. 31.

    , & Entorhinal cortex grid cells can map to hippocampal place cells by competitive learning. Network 17, 447–465 (2006).

  32. 32.

    & Hebbian analysis of the transformation of medial entorhinal grid-cell inputs to hippocampal place fields. J. Neurophysiol. 103, 3167–3183 (2010).

  33. 33.

    et al. Optogenetric dissection of entorhinal-hippocampal functional connectivity. Science 340, 1232627 (2013).

  34. 34.

    Intrinsic projections of the retrohippocampal region in the rat brain. I. The subicular complex. J. Comp. Neurol. 236, 504–522 (1985).

  35. 35.

    et al. Grid cells in pre- and parasubiculum. Nat. Neurosci. 13, 987–994 (2010).

  36. 36.

    et al. Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network. Science 317, 94–99 (2007).

  37. 37.

    & The cognitive neuroscience of remembering. Nat. Rev. Neurosci. 2, 624–634 (2001).

  38. 38.

    & Distinct pathways for rule-based retrieval and spatial mapping of memory representations in hippocampal neurons. J. Neurosci. 33, 1002–1013 (2013).

  39. 39.

    , , & Nucleus reuniens of the midline thalamus: link between the medial prefrontal cortex and the hippocampus. Brain Res. Bull. 71, 601–609 (2007).

  40. 40.

    & A neural circuit for memory specificity and generalization. Science 339, 1290–1295 (2013).

  41. 41.

    , , & Representation of behavioral context in the nucleus reuniens for CA1 place cells. Soc. Neurosci. Abstr. 702.04 (2013).

  42. 42.

    , , & Efferent connections of the prelimbic (area 32) and the infralimbic (area 25) cortices: an anterograde tracing study in the cat. J. Comp. Neurol. 242, 40–55 (1985).

  43. 43.

    & Cortical afferents of the perirhinal, postrhinal, and entorhinal cortices of the rat. J. Comp. Neurol. 398, 179–205 (1998).

  44. 44.

    & Entorhinal cortex of the rat: organization of intrinsic connections. J. Comp. Neurol. 398, 49–82 (1998).

  45. 45.

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

  46. 46.

    , & The mechanism of rate remapping in the dentate gyrus. Neuron 68, 1051–1058 (2010).

  47. 47.

    & Place cell discharge is extremely variable during individual passes of the rat through the firing field. Proc. Natl. Acad. Sci. USA 95, 3182–3187 (1998).

  48. 48.

    , , , & Increased attention to spatial context increases both place field stability and spatial memory. Neuron 42, 283–295 (2004).

  49. 49.

    , , , & Theta-paced flickering between place-cell maps in the hippocampus. Nature 478, 246–249 (2011).

  50. 50.

    , , & Dynamics of memory representations in networks with novelty-facilitated synaptic plasticity. Neuron 52, 383–394 (2006).

  51. 51.

    , , & Theta phase precession in hippocampal neuronal populations and the compression of temporal sequences. Hippocampus 6, 149–172 (1996).

Download references

Acknowledgements

We thank A.M. Amundgård, K. Haugen, K. Jenssen, E. Kråkvik, R. Skjerpeng and H. Waade for technical assistance. This work was supported by the Kavli Foundation and a Centre of Excellence grant from the Research Council of Norway.

Author information

Author notes

    • Li Lu
    •  & Jill K Leutgeb

    These authors contributed equally to this work.

Affiliations

  1. Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Trondheim, Norway.

    • Li Lu
    • , Jill K Leutgeb
    • , Albert Tsao
    • , Espen J Henriksen
    • , Stefan Leutgeb
    • , Carol A Barnes
    • , Menno P Witter
    • , May-Britt Moser
    •  & Edvard I Moser
  2. Neurobiology Section and Center for Neural Circuits and Behavior, Division of Biological Sciences, University of California, San Diego, La Jolla, California, USA.

    • Jill K Leutgeb
    •  & Stefan Leutgeb
  3. Evelyn F. McKnight Brain Institute, Division of Neural Systems, Memory and Aging, University of Arizona, Tucson, Arizona, USA.

    • Carol A Barnes

Authors

  1. Search for Li Lu in:

  2. Search for Jill K Leutgeb in:

  3. Search for Albert Tsao in:

  4. Search for Espen J Henriksen in:

  5. Search for Stefan Leutgeb in:

  6. Search for Carol A Barnes in:

  7. Search for Menno P Witter in:

  8. Search for May-Britt Moser in:

  9. Search for Edvard I Moser in:

Contributions

J.K.L., S.L., E.I.M. and M.-B.M. conceived and designed the experiment. E.J.H. made lesions. S.L., L.L. and E.J.H. implanted hippocampal tetrodes. J.K.L., L.L. and E.J.H. performed the hippocampal recording experiments. J.K.L., L.L. and S.L. analyzed the hippocampal data. A.T. implanted LEC tetrodes and recorded and analyzed LEC cells. L.L. made figures. L.L., E.J.H. and M.P.W. evaluated lesions and made unfolded maps. A.T., E.J.H., L.L. and M.P.W. determined LEC recording locations. M.P.W. carried out tracing experiments and analyses. E.I.M. and L.L. wrote the manuscript. M.-B.M. and E.I.M. supervised and coordinated the project. All of the authors contributed to discussion and interpretation.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Li Lu or Jill K Leutgeb or Edvard I Moser.

Supplementary information

PDF files

  1. 1.

    Supplementary Figures and Text

    Supplementary Figures 1-11 and Supplementary Table 1

Excel files

  1. 1.

    Supplementary Table 2

    Source data for supplementary figures.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nn.3462

Further reading