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Vol. 29, No. 1-2, 2007
Issue release date: December 2006
Section title: Mini Review
Free Access
Dev Neurosci 2007;29:14–27
(DOI:10.1159/000096208)

Ectopic Granule Cells of the Rat Dentate Gyrus

Scharfman H.a, b · Goodman J.b · McCloskey D.b
aDepartments of Pharmacology and Neurology, Columbia University, New York, N.Y., and bCenter for Neural Recovery and Rehabilitation Research, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, N.Y., USA
email Corresponding Author

Abstract

Granule cells of the mammalian dentate gyrus normally form a discrete layer, and virtually all granule cells migrate to this location. Exceptional granule cells that are positioned incorrectly, in ‘ectopic’ locations, are rare. Although the characteristics of such ectopic granule cells appear similar in many respects to granule cells located in the granule cell layer, their rare occurrence has limited a full evaluation of their structure and function. More information about ectopic granule cells has been obtained by studying those that develop after experimental manipulations that increase their number. For example, after severe seizures, the number of ectopic granule cells located in the hilus increases dramatically. These experimentally-induced ectopic granule cells may not be equivalent to normal ectopic granule cells necessarily, but the vastly increased numbers have allowed much more information to be obtained. Remarkably, the granule cells that are positioned ectopically develop intrinsic properties and an axonal projection that are similar to granule cells that are located normally, i.e., in the granule cell layer. However, dendritic structure and synaptic structure/function appear to differ. These studies have provided new insight into a rare type of granule cell in the dentate gyrus, and the plastic characteristics of dentate granule cells that appear to depend on the location of the cell body.

© 2007 S. Karger AG, Basel


  

Key Words

  • Neurogenesis
  • Hilus
  • Seizure
  • Epilepsy
  • Hippocampus
  • Neuronal migration
  • Calbindin
  • PROX1

References

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  2. Acsady L, Katona I, Martinez-Guijarro FJ, Buzsáki G, Freund TF (2000): Unusual target selectivity of perisomatic inhibitory cells in the hilar region of the rat hippocampus. J Neurosci 20:6907–6919.
  3. Amaral DG (1978): A Golgi study of cell types in the hilar region of the hippocampus in the rat. J Comp Neurol 182:851–914.
  4. Amaral DG (1979): Synaptic extensions from the mossy fibers of the fascia dentata. Anat Embryol 155:241–251.
  5. Amaral DG, Woodward DJ (1977): A hippocampal interneuron observed in the inferior region. Brain Res 124:225–236.
  6. Bagri A, Gurney T, He X, Zou YR, Littman DR, Tessier-Lavigne M, Pleasure SJ (2002): The chemokine SDF1 regulates migration of dentate granule cells. Development 129:4249–4260.
  7. Bayer SA (1980): Development of the hippocampal region in the rat. 1. Neurogenesis examined with [3H]thymidine autoradiography. J Comp Neurol 190:87–114.
  8. Blackstad TW, Kjaerheim A (1961): Special axo-dendritic synapses in the hippocampal cortex: electron and light microscopic studies on the layer of mossy fibers. J Comp Neurol 117:133–159.
  9. Boss BD, Peterson GM, Cowan WM (1985): On the number of neurons in the dentate gyrus of the rat. Brain Res 338:144–150.
  10. Cameron HA, Hazel TG, McKay RD (1998): Regulation of neurogenesis by growth factors and neurotransmitters. J Neurobiol 36:287–306.
  11. Cha BH, Akman C, Silveira DC, Liu X, Holmes GL (2004): Spontaneous recurrent seizure following status epilepticus enhances dentate gyrus neurogenesis. Brain Dev 26:394–397.
  12. 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 246:435–458.
  13. Claiborne BM, Amaral DG, Cowan WM (1990): Quantitative, three-dimensional analysis of granule cell dendrites in the rat dentate gyrus. J Comp Neurol 302:206–219.
  14. Dashtipour K, Tran PH, Okazaki MM, Nadler JV, Ribak CE (2001): Ultrastructural features and synaptic connections of hilar ectopic granule cells in the rat dentate gyrus are different from those of granule cells in the granule cell layer. Brain Res 890:261–271.
  15. Elliott RC, Khademi S, Pleasure SJ, Parent JM, Lowenstein DH (2001): Differential regulation of basic helix-loop-helix mRNAs in the dentate gyrus following status epilepticus. Neuroscience 106:79–88.
  16. Farrar CE, Huang CS, Clarke SG, Houser CR (2005): Increased cell proliferation and granule cell number in the dentate gyrus of protein repair-deficient mice. J Comp Neurol 493:524–537.
  17. Forster E, Zhao S, Frotscher M (2006): Laminating the hippocampus. Nat Rev Neurosci 7:259–268.
  18. Frotscher M (1997): Dual role of Cajal-Retzius cells and reelin in cortical development. Cell Tissue Res 290:315–322.
  19. Gaarskjaer FB, Laurberg S (1983): Ectopic granule cells of hilus fasciae dentatae projecting to the ipsilateral region inferior of the rat hippocampus. Brain Res 274:11–16.
  20. Goodman JH, Wasterlain CG, Massarweh WF, Dean E, Sollas AL, Sloviter RS (1993): Calbindin-D28k immunoreactivity and selective vulnerability to ischemia in the dentate gyrus of the developing rat. Brain Res 606:309–314.
  21. Green EJ, Juraska JM (1985): The dendritic morphology of hippocampal dentate granule cells varies with their position in the granule cell layer: a quantitative Golgi study. Exp Brain Res 59:582–586.
  22. Haas CA, Dudeck O, Kirsch M, Huszka C, Kann G, Pollak S, Zenter J, Frotscher M (2002): Role for reelin in the development of granule cell dispersion in temporal lobe epilepsy. J Neurosci 22:5797–5802.
  23. Hamlyn LH (1962): The fine structure of the mossy fiber endings in the hippocampus of the rabbit. J Anat 6:112–120.
  24. Hattiangady B, Rao MS, Shetty AK (2004): Chronic temporal lobe epilepsy is associated with severely declined dentate neurogenesis in the adult hippocampus. Neurobiol Dis 17:473–490.
  25. Huttmann K, Sadgrove M, Wallraff A, Hinterkeuser S, Kirchhoff F, Steinhauser C, Gray WP (2003): Seizures preferentially stimulate proliferation of radial glia-like astrocytes in the adult dentate gyrus: functional and immunocytochemical analysis. Eur J Neurosci 18:2769–2778.
  26. Ishizuka N, Weber J, Amaral DG (1990): Organization of intrahippocampal projections originating from CA3 pyramidal cells in the rat. J Comp Neurol 295:580–623.
  27. Jessberger S, Romer B, Babu H, Kempermann G (2005): Seizures induce proliferation and dispersion of doublecortin-positive hippocampal progenitor cells. Exp Neurol 196:342–351.
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  30. Kempermann G (2005): Adult Neurogenesis: Stem Cells and Neuronal Development in the Adult Brain. New York, Oxford University Press.
  31. Li XG, Somogyi P, Ylinen A, Buzsáki G (1994): The hippocampal CA3 network: an in vivo intracellular labeling study. J Comp Neurol 339:181–208.
  32. Lichtenwalner RJ, Forbes ME, Bennett SA, Lynch CD, Sonntag WE, Riddle DR (2001): Intracerebroventricular infusion of insulin-like growth factor-I ameliorates the age-related decline in hippocampal neurogenesis. Neuroscience 107:603–613.
  33. Lu M, Grove EA, Miller RJ (2002): Abnormal development of the hippocampal dentate gyrus in mice lacking the CXCR4 chemokine receptor. Proc Natl Acad Sci USA 99:7090–7095.
  34. Lübbers K, Frotscher M (1987): Fine structure and synaptic connections of identified neurons in the rat fascia dentata. Anat Embryol 177:1–14.
  35. Lübke J, Frotscher M, Spruston N (1998): Specialized electrophysiological properties of anatomically identified neurons in the hilar region of the rat fascia dentata. J Neurophysiol 79:1518–1534.
  36. Magloczky Z, Halasz P, Vajda J, Czirjak S, Freund TF (1997): Loss of Calbindin-D28K immunoreactivity from dentate granule cells in human temporal lobe epilepsy. Neuroscience 76:377–385.
  37. Marti-Subirana A, Soriano E, Garcia-Verdugo JM (1986): Morphological aspects of the ectopic granule-like cellular population in the albino rat hippocampal formation: a Golgi study. J Anat 144:31–47.
  38. McCloskey DP, Hintz T, Pierce JP, Scharfman HE (2005): Stereological estimation of the number of ectopic granule cells (EGCs) in the hilus following pilocarpine-induced status epilepticus (PILO). Epilepsia 46:295–296.

    External Resources

  39. Minami M, Maekawa K, Yamakuni H, Katayama T, Nakamura J, Satoh M (2002): Kainic acid induces leukemia inhibitory factor mRNA expression in the rat brain: differences in the time course of mRNA expression between the dentate gyrus and pal CA1/CA3 subfields. Brain Res Mol Brain Res 107:39–46.
  40. Mohapel P, Ekdahl CT, Lindvall O (2004): Status epilepticus severity influences the long-term outcome of neurogenesis in the adult dentate gyrus. Neurobiol Dis 15:196–205.
  41. Monje ML, Toda H, Palmer TD (2003): Inflammatory blockade restores adult hippocampal neurogenesis. Science 302:1760–1765.
  42. Nagerl UV, Mody I, Jeub M, Lie AA, Elger CE, Beck H (2000): Surviving granule cells of the sclerotic human hippocampus have reduced Ca2+ influx because of a loss of calbindin-D(28k) in temporal lobe epilepsy. J Neurosci 20:1831–1836.
  43. Nek N, Schwegler H, Crusio WE, Frotscher M (1993): Are the fine-structural characteristics of mouse hippocampal mossy fiber synapses determined by the density of mossy fiber axons? Neurosci Lett 158:756–778.

    External Resources

  44. Overstreet-Wadiche LS, Bensen AL, Westbrook GL (2006): Delayed development of adult-generated granule cells in dentate gyrus. J Neurosci 26:2326–2334.
  45. Palmer TD, Willhoite AR, Gage FH (2000): Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 425:479–494.
  46. Parent JM, Elliot RC, Pleasure SJ, Barbaro NM, Lowenstein DH (2006): Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy. Ann Neurol 59:81–91.
  47. Parent JM, Yu TW, Leibowitz RT, Geschwind DH, Sloviter RS, Lowenstein DH (1997): Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci 17:3727–3738.
  48. Patel LS, Wenzel HJ, Schwartzkroin PA (2004): Physiological and morphological characterization of dentate granule cells in the p35 knock-out mouse hippocampus: evidence for an epileptic circuit. J Neurosci 24:9005–9014.
  49. Patrylo PR, Browning RA, Cranick S (2006): Reeler homozygous mice exhibit enhanced susceptibility to epileptiform activity. Epilepsia 47:257–266.
  50. Pierce JP, Melton J, Punsoni M, McCloskey DP, Scharfman HE (2005): Mossy fibers are the primary source of afferent input to ectopic granule cells that are born after pilocarpine-induced seizures. Exp Neurol 196:316–331.
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  52. Scharfman HE (1992): Differentiation of rat dentate neurons by morphology and electrophysiology in hippocampal slices: granule cells, spiny hilar cells and aspiny ‘fast-spiking’ cells. Epilepsy Res Suppl 7:93–109.
  53. Scharfman HE (1993): Spiny neurons of area CA3c in rat hippocampal slices have similar electrophysiological characteristics and synaptic responses despite morphological variation. Hippocampus 3:9–28.
  54. Scharfman HE (1994a): EPSPs of dentate gyrus granule cells during epileptiform bursts of dentate hilar ‘mossy’ cells and area CA3 pyramidal cells in disinhibited rat hippocampal slices. J Neurosci 14:6041–6057.
  55. Scharfman HE (1994b): Evidence from simultaneous intracellular recordings in rat hippocampal slices that area CA3 pyramidal cells innervate dentate hilar mossy cells. J Neurophysiol 72:2167–2180.
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    External Resources

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Author Contacts

Helen Scharfman
CNRRR Department, Helen Hayes Hospital
Rte 9W
West Haverstraw, NY 10993-1195 (USA)
Tel. +1 845 786 4859, Fax +1 845 786 4875, E-Mail scharfmanh@helenhayeshosp.org

  

Article Information

Received: February 15, 2006
Accepted: April 5, 2006
Number of Print Pages : 14
Number of Figures : 5, Number of Tables : 0, Number of References : 75

  

Publication Details

Developmental Neuroscience

Vol. 29, No. 1-2, Year 2007 (Cover Date: December 2006)

Journal Editor: Campagnoni, A.T. (Los Angeles, Calif.)
ISSN: 0378–5866 (print), 1421–9859 (Online)

For additional information: http://www.karger.com/DNE


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References

  1. Åberg M, Åberg ND, Hedbacker H, Oscarsson J, Eriksson PS (2000): Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus. J Neurosci 20:2896–2903.
  2. Acsady L, Katona I, Martinez-Guijarro FJ, Buzsáki G, Freund TF (2000): Unusual target selectivity of perisomatic inhibitory cells in the hilar region of the rat hippocampus. J Neurosci 20:6907–6919.
  3. Amaral DG (1978): A Golgi study of cell types in the hilar region of the hippocampus in the rat. J Comp Neurol 182:851–914.
  4. Amaral DG (1979): Synaptic extensions from the mossy fibers of the fascia dentata. Anat Embryol 155:241–251.
  5. Amaral DG, Woodward DJ (1977): A hippocampal interneuron observed in the inferior region. Brain Res 124:225–236.
  6. Bagri A, Gurney T, He X, Zou YR, Littman DR, Tessier-Lavigne M, Pleasure SJ (2002): The chemokine SDF1 regulates migration of dentate granule cells. Development 129:4249–4260.
  7. Bayer SA (1980): Development of the hippocampal region in the rat. 1. Neurogenesis examined with [3H]thymidine autoradiography. J Comp Neurol 190:87–114.
  8. Blackstad TW, Kjaerheim A (1961): Special axo-dendritic synapses in the hippocampal cortex: electron and light microscopic studies on the layer of mossy fibers. J Comp Neurol 117:133–159.
  9. Boss BD, Peterson GM, Cowan WM (1985): On the number of neurons in the dentate gyrus of the rat. Brain Res 338:144–150.
  10. Cameron HA, Hazel TG, McKay RD (1998): Regulation of neurogenesis by growth factors and neurotransmitters. J Neurobiol 36:287–306.
  11. Cha BH, Akman C, Silveira DC, Liu X, Holmes GL (2004): Spontaneous recurrent seizure following status epilepticus enhances dentate gyrus neurogenesis. Brain Dev 26:394–397.
  12. 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 246:435–458.
  13. Claiborne BM, Amaral DG, Cowan WM (1990): Quantitative, three-dimensional analysis of granule cell dendrites in the rat dentate gyrus. J Comp Neurol 302:206–219.
  14. Dashtipour K, Tran PH, Okazaki MM, Nadler JV, Ribak CE (2001): Ultrastructural features and synaptic connections of hilar ectopic granule cells in the rat dentate gyrus are different from those of granule cells in the granule cell layer. Brain Res 890:261–271.
  15. Elliott RC, Khademi S, Pleasure SJ, Parent JM, Lowenstein DH (2001): Differential regulation of basic helix-loop-helix mRNAs in the dentate gyrus following status epilepticus. Neuroscience 106:79–88.
  16. Farrar CE, Huang CS, Clarke SG, Houser CR (2005): Increased cell proliferation and granule cell number in the dentate gyrus of protein repair-deficient mice. J Comp Neurol 493:524–537.
  17. Forster E, Zhao S, Frotscher M (2006): Laminating the hippocampus. Nat Rev Neurosci 7:259–268.
  18. Frotscher M (1997): Dual role of Cajal-Retzius cells and reelin in cortical development. Cell Tissue Res 290:315–322.
  19. Gaarskjaer FB, Laurberg S (1983): Ectopic granule cells of hilus fasciae dentatae projecting to the ipsilateral region inferior of the rat hippocampus. Brain Res 274:11–16.
  20. Goodman JH, Wasterlain CG, Massarweh WF, Dean E, Sollas AL, Sloviter RS (1993): Calbindin-D28k immunoreactivity and selective vulnerability to ischemia in the dentate gyrus of the developing rat. Brain Res 606:309–314.
  21. Green EJ, Juraska JM (1985): The dendritic morphology of hippocampal dentate granule cells varies with their position in the granule cell layer: a quantitative Golgi study. Exp Brain Res 59:582–586.
  22. Haas CA, Dudeck O, Kirsch M, Huszka C, Kann G, Pollak S, Zenter J, Frotscher M (2002): Role for reelin in the development of granule cell dispersion in temporal lobe epilepsy. J Neurosci 22:5797–5802.
  23. Hamlyn LH (1962): The fine structure of the mossy fiber endings in the hippocampus of the rabbit. J Anat 6:112–120.
  24. Hattiangady B, Rao MS, Shetty AK (2004): Chronic temporal lobe epilepsy is associated with severely declined dentate neurogenesis in the adult hippocampus. Neurobiol Dis 17:473–490.
  25. Huttmann K, Sadgrove M, Wallraff A, Hinterkeuser S, Kirchhoff F, Steinhauser C, Gray WP (2003): Seizures preferentially stimulate proliferation of radial glia-like astrocytes in the adult dentate gyrus: functional and immunocytochemical analysis. Eur J Neurosci 18:2769–2778.
  26. Ishizuka N, Weber J, Amaral DG (1990): Organization of intrahippocampal projections originating from CA3 pyramidal cells in the rat. J Comp Neurol 295:580–623.
  27. Jessberger S, Romer B, Babu H, Kempermann G (2005): Seizures induce proliferation and dispersion of doublecortin-positive hippocampal progenitor cells. Exp Neurol 196:342–351.
  28. Jin K, Zhu Y, Sun Y, Mao XO, Lin X, Greenberg DA (2002): Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc Natl Acad Sci USA 99:11946–11950.
  29. Jung KH, Chu K, Kim M, Jeong SW, Song YM, et al. (2004): Continuous cytosine-b-D-arabinofuranoside infusion reduces ectopic granule cells in adult rat hippocampus with attenuation of spontaneous recurrent seizures following pilocarpine-induced status epilepticus. Eur J Neurosci 19:3219–3226.
  30. Kempermann G (2005): Adult Neurogenesis: Stem Cells and Neuronal Development in the Adult Brain. New York, Oxford University Press.
  31. Li XG, Somogyi P, Ylinen A, Buzsáki G (1994): The hippocampal CA3 network: an in vivo intracellular labeling study. J Comp Neurol 339:181–208.
  32. Lichtenwalner RJ, Forbes ME, Bennett SA, Lynch CD, Sonntag WE, Riddle DR (2001): Intracerebroventricular infusion of insulin-like growth factor-I ameliorates the age-related decline in hippocampal neurogenesis. Neuroscience 107:603–613.
  33. Lu M, Grove EA, Miller RJ (2002): Abnormal development of the hippocampal dentate gyrus in mice lacking the CXCR4 chemokine receptor. Proc Natl Acad Sci USA 99:7090–7095.
  34. Lübbers K, Frotscher M (1987): Fine structure and synaptic connections of identified neurons in the rat fascia dentata. Anat Embryol 177:1–14.
  35. Lübke J, Frotscher M, Spruston N (1998): Specialized electrophysiological properties of anatomically identified neurons in the hilar region of the rat fascia dentata. J Neurophysiol 79:1518–1534.
  36. Magloczky Z, Halasz P, Vajda J, Czirjak S, Freund TF (1997): Loss of Calbindin-D28K immunoreactivity from dentate granule cells in human temporal lobe epilepsy. Neuroscience 76:377–385.
  37. Marti-Subirana A, Soriano E, Garcia-Verdugo JM (1986): Morphological aspects of the ectopic granule-like cellular population in the albino rat hippocampal formation: a Golgi study. J Anat 144:31–47.
  38. McCloskey DP, Hintz T, Pierce JP, Scharfman HE (2005): Stereological estimation of the number of ectopic granule cells (EGCs) in the hilus following pilocarpine-induced status epilepticus (PILO). Epilepsia 46:295–296.

    External Resources

  39. Minami M, Maekawa K, Yamakuni H, Katayama T, Nakamura J, Satoh M (2002): Kainic acid induces leukemia inhibitory factor mRNA expression in the rat brain: differences in the time course of mRNA expression between the dentate gyrus and pal CA1/CA3 subfields. Brain Res Mol Brain Res 107:39–46.
  40. Mohapel P, Ekdahl CT, Lindvall O (2004): Status epilepticus severity influences the long-term outcome of neurogenesis in the adult dentate gyrus. Neurobiol Dis 15:196–205.
  41. Monje ML, Toda H, Palmer TD (2003): Inflammatory blockade restores adult hippocampal neurogenesis. Science 302:1760–1765.
  42. Nagerl UV, Mody I, Jeub M, Lie AA, Elger CE, Beck H (2000): Surviving granule cells of the sclerotic human hippocampus have reduced Ca2+ influx because of a loss of calbindin-D(28k) in temporal lobe epilepsy. J Neurosci 20:1831–1836.
  43. Nek N, Schwegler H, Crusio WE, Frotscher M (1993): Are the fine-structural characteristics of mouse hippocampal mossy fiber synapses determined by the density of mossy fiber axons? Neurosci Lett 158:756–778.

    External Resources

  44. Overstreet-Wadiche LS, Bensen AL, Westbrook GL (2006): Delayed development of adult-generated granule cells in dentate gyrus. J Neurosci 26:2326–2334.
  45. Palmer TD, Willhoite AR, Gage FH (2000): Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 425:479–494.
  46. Parent JM, Elliot RC, Pleasure SJ, Barbaro NM, Lowenstein DH (2006): Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy. Ann Neurol 59:81–91.
  47. Parent JM, Yu TW, Leibowitz RT, Geschwind DH, Sloviter RS, Lowenstein DH (1997): Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci 17:3727–3738.
  48. Patel LS, Wenzel HJ, Schwartzkroin PA (2004): Physiological and morphological characterization of dentate granule cells in the p35 knock-out mouse hippocampus: evidence for an epileptic circuit. J Neurosci 24:9005–9014.
  49. Patrylo PR, Browning RA, Cranick S (2006): Reeler homozygous mice exhibit enhanced susceptibility to epileptiform activity. Epilepsia 47:257–266.
  50. Pierce JP, Melton J, Punsoni M, McCloskey DP, Scharfman HE (2005): Mossy fibers are the primary source of afferent input to ectopic granule cells that are born after pilocarpine-induced seizures. Exp Neurol 196:316–331.
  51. Ramón y Cajal S (1911): Fourth-order olfactory areas: Ammons horn and the dentate gyrus; in: Histologie du système nerveux de l’homme et des vertébrés. Paris, Maloine, vol 2.
  52. Scharfman HE (1992): Differentiation of rat dentate neurons by morphology and electrophysiology in hippocampal slices: granule cells, spiny hilar cells and aspiny ‘fast-spiking’ cells. Epilepsy Res Suppl 7:93–109.
  53. Scharfman HE (1993): Spiny neurons of area CA3c in rat hippocampal slices have similar electrophysiological characteristics and synaptic responses despite morphological variation. Hippocampus 3:9–28.
  54. Scharfman HE (1994a): EPSPs of dentate gyrus granule cells during epileptiform bursts of dentate hilar ‘mossy’ cells and area CA3 pyramidal cells in disinhibited rat hippocampal slices. J Neurosci 14:6041–6057.
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    External Resources

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