Skip to main content
SpringerLink
Log in

New spines, new memories

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

For more than a century dendritic spines have been a source of fascination and speculation. The long-held belief that these anatomical structures are involved in learning and memory are addressed. Specifically, two lines of evidence that support this claim are reviewed. In the first, we review evidence that experimental manipulations that affect dendritic spine number in the hippocampus also affect learning processes of various sorts. In the second, we review evidence that learning itself affects the presence of dendritic spines in the hippocampus. Based on these observations, we propose that the presence of spines enhances synaptic efficacy and thereby the excitability of the network involved in the learning process. With this scheme, learning is not dependent on changes in spine density but rather changes in the presence of dendritic spines provide anatomical support for the processing of novel information used in memory formation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ramon y Cajal S. (1893). Neue Darstellung vom histologischen Bau des Centralnerven system. Arch. Anat. Physiol. 17, 319–428.

    Google Scholar 

  2. Andersen P., Balckstad T. W., and Lomo T. (1966). Location and identification of excitatory synapses on hippocampal pyramidal cells. Exp. Brain Res. 1, 236–248.

    Article  PubMed  CAS  Google Scholar 

  3. Sorra K. E. and Harris K. M. (2000). Overview on the structure, composition, function, development, and plasticity of hippocampal dendritic spines. Hippocampus 10, 501–511.

    Article  PubMed  CAS  Google Scholar 

  4. Greenough W. T., Juraska J. M., and Volkmar F. R. (1979). Maze training effects on dendritic branching in occipital cortex of adult rats. Behav. Neural Biol. 26, 287–297.

    Article  PubMed  CAS  Google Scholar 

  5. Bailey C. H. and Kandel E. R. (1993). Structural changes accompanying memory storage. Annu. Rev. Physiol. 55, 397–426.

    Article  PubMed  CAS  Google Scholar 

  6. Gould E., Woolley C. S., Frankfurt M., and McEwen B. S. (1990). Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood. J. Neurosci. 10, 1286–1291.

    PubMed  CAS  Google Scholar 

  7. Woolley C. S. and McEwen B. S. (1993). Role of estradiol and progesterone in regulation of hippocampal dendritic spine density during the estrous cycle in the rat. J. Comp. Neurol. 336, 293–306.

    Article  PubMed  CAS  Google Scholar 

  8. Shors T. J., Chua C., and Falduto J. (2001). Sex differences and opposite effects of stress on dendritic spine density in the male versus female hippocampus. J. Neurosci. 21, 6292–9297.

    PubMed  CAS  Google Scholar 

  9. Shors T. J., Falduto J., Leuner B. (2004). The opposite effects of stress on dendritic spines in male vs. female rats are NMDA receptor-dependent. Eur. J. Neurosci. 19, 145–150.

    Article  PubMed  CAS  Google Scholar 

  10. Woolley C. S., Gould E., Frankfurt M., and McEwen B. S. (1990). Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons. J. Neurosci. 10, 4035–4039.

    PubMed  CAS  Google Scholar 

  11. Woolley C. S. and McEwen B. S. (1992). Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat. J. Neurosci. 12, 2549–2254.

    PubMed  CAS  Google Scholar 

  12. Klintsova A., Levy W. B., and Desmond N. L. (1995). Astrocytic volume fluctuates in the hippocampal CA1 region across the estrous cycle. Brain Res. 690, 269–274.

    Article  PubMed  CAS  Google Scholar 

  13. Leranth C., Shanabrough M., and Redmond D. E., Jr (2002). Gonadal hormones are responsible for maintaining the integrity of spine synapses in the CA1 hippocampal subfield of female nonhuman primate. J. Comp. Neurol. 447, 34–42.

    Article  PubMed  CAS  Google Scholar 

  14. Bloch G. J. and Gorski R. A. (1988). Estrogen/progesterone treatment in adulthood affects the size of several components of the medial preoptic area in the male rat. J. Comp. Neurol. 275, 613–622.

    Article  PubMed  CAS  Google Scholar 

  15. Matsumoto A. (1991). Synaptogenic action of sex steroids in developing and adult neuroendocrine brain. Psychoneuroendocrinology 16, 25–40.

    Article  PubMed  CAS  Google Scholar 

  16. Shors T. J., Lewczyk C., Pacynski M., Matthew P. R., and Pickett J. (1998). Stages of estrus mediate the stress-induced impairment of associative learning in the female rat. Neuroreport 9, 419–423.

    Article  PubMed  CAS  Google Scholar 

  17. Wood G. E., Beylin A., and Shors T. J. (2001). The contribution of adrenal and reproductive hormones to the sexually opposed effects of stress on trace conditioning. Behav. Neurosci. 115, 1–13.

    Article  Google Scholar 

  18. Sandstrom N. L. and Williams C. L. (2001). Memory retention is modulated by acute estradiol and progesterone replacement. Behav. Neurosci. 115, 384–393.

    Article  PubMed  CAS  Google Scholar 

  19. Leranth C., Petnehazy O., and MacLusky N. J. (2003). Gonadal hormones affect spine synaptic density in the CA1 hippocampal subfield of male rats. J. Neurosci. 23, 1588–1592.

    PubMed  CAS  Google Scholar 

  20. Frye C. A. and Seliga A. M. (2001). Testosterone increases analgesia, anxiolysis, and cognitive performance of male rats. Cogn. Affect. Behav. Neurosci. 1, 371–381.

    PubMed  CAS  Google Scholar 

  21. Cherrier M. M., Anawalt B. D., Herbst K. L., Amory J. K., Craft S., Matsumoto A. M., and Bremner W. J. (2001). Cognitive effects of short-term manipulation of serum sex steroids in healthy young men. J. Clin. Endocrinol. Metab. 87, 3090–3096.

    Article  Google Scholar 

  22. Wood G. E. and Shors T. J. (1998). Stress facilitates classical conditioning in males but impairs conditioning in females through the activational influences of ovarian hormones. Proc. Natl. Acad. Sci. USA 95, 4066–4071.

    Article  PubMed  CAS  Google Scholar 

  23. Greenough W. T., Wood W. E., and Madden T. C. (1972). Possible memory storage differences among mice reared in environments varying in complexity. Behav. Biol. 7, 717–722.

    Article  PubMed  CAS  Google Scholar 

  24. Moser M. B., Trommald M., and Andersen P. (1994). An increase in dendritic spine density on hippocampal CA1 pyramidal cells following spatial learning in adult rats suggests the formation of new synapses. Proc. Natl. Acad. Sci. USA 91, 12,673–12,675.

    Article  CAS  Google Scholar 

  25. Rampon C., Tang Y. P., Goodhouse J., Shimizu E., Kyin M., and Tsien J. Z. (2000). Enrichment induces structural changes and recovery from nonspatial memory deficits in CA1 NMDAR1-knockout mice. Nat. Neurosci. 3, 238–244.

    Article  PubMed  CAS  Google Scholar 

  26. Moser M. B., Trommald M., Egeland T., and Andersen P. (1997). Spatial training in a complex environment and isolation alter the spine distribution differentially in rat CA1 pyramidal cells. J. Comp. Neurol. 380, 373–381.

    Article  PubMed  CAS  Google Scholar 

  27. Globus A., Rosenzweig M. R., Bennett E. L., and Diamond M. C. (1973). Effects of differential experience on dendritic spine counts in rat cerebral cortex. J. Comp. Physiol. Psych. 82, 175–181.

    Article  CAS  Google Scholar 

  28. O’Malley A., O’Connell C., and Regan C. M. (1998). Ultrastructural analysis reveals avoidance conditioning to induce a transient increase in hippocampal dentate spine density in the 6 hour post-training period of consolidation. Neuroscience 87, 607–613.

    Article  PubMed  CAS  Google Scholar 

  29. O’Malley A., O’Connell C., Murphy K. J., and Regan C. M. (2000). Transient spine density increases in the mid-molecular layer of hippocampal dentate gyrus accompany consolidation of a spatial learning task in the rodent. Neuroscience 99, 229–232.

    Article  PubMed  CAS  Google Scholar 

  30. Rusakov D. A., Davies H. A., Harrison E., Diana G., Richter-Levin G., Bliss T. V. P., and Stewart M. G. (1997). Ultrastructural synaptic correlates of spatial learning in rat hippocampus. Neuroscience 80, 69–77.

    Article  PubMed  CAS  Google Scholar 

  31. Solomon P. R., VanderSchaaf E. R., Thompson R. F., and Weisz D. J. (1986). Hippocampus and trace conditioning of the rabbit’s classically conditioned nictitating membrane response. Behav. Neurosci. 100, 729–744.

    Article  PubMed  CAS  Google Scholar 

  32. Moyer J. R., Jr Deyo R. A., and Disterhoft J. F. (1990). Hippocampectomy disrupts trace eye-blink conditioning in rabbits. Behav. Neurosci. 104, 243–252.

    Article  PubMed  Google Scholar 

  33. Beylin A. V., Gandhi C. C., Wood G., Talk A. C., Matzel L. D., and Shors T. J. (2001). The role of the hippocampus in trace conditioning: temporal discontiguity or task difficulty? Neurobio. Learn. Mem. 76, 447–461.

    Article  CAS  Google Scholar 

  34. Leuner B., Faldtuo J., and Shors T. J. (2003). Associative memory formation increases the observation of dendritic spines in the hippocampus. J. Neurosci. 23, 659–665.

    PubMed  CAS  Google Scholar 

  35. Servatius R. J. and Shors T. J. (1996) Early acquisition, but not retention, of the classically conditioned eyeblink response is N-Methyl-d-Aspartate (NMDA) receptor dependent. Behav. Neurosci. 110, 1040–1048.

    Article  PubMed  CAS  Google Scholar 

  36. Thompson L. T. and Disterhoft J. F. (1997). N-Methyl-d-Aspartate receptors in associative eye-blink conditioning: both MK-801 and Phencyclidine produce task and dose dependent impairments. J. Pharmacol. Exp. Ther. 281, 928–940.

    PubMed  CAS  Google Scholar 

  37. Berger T. W., Clark G. A., and Thompson R. F. (1980). Learning-dependent neuronal responses recorded from limbic system brain structures during classical conditioning. Physiol. Psychol. 8, 155–167.

    Google Scholar 

  38. Anderson B. J., Relucio K., Haglund K., Logan C., Knowlton B., Thompson J., Steinmetz J. E., Thompson R. F., and Greenough W. T. (1999). Effects of paired and unpaired eye-blink conditioning on Purkinje cell morphology. Learn. Mem. 6, 128–137.

    PubMed  CAS  Google Scholar 

  39. Maletic-Savatic M., Malinow R., and Svoboda K. (1999). Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity. Science 283, 1923–1927.

    Article  PubMed  CAS  Google Scholar 

  40. Engert F. and Bonhoeffer T. (1999). Dendritic spine changes associated with hippocampal long-term synaptic plasticity. Nature 399, 66–70.

    Article  PubMed  CAS  Google Scholar 

  41. Tocco G., Annala A. J., Baudry M., and Thompson R. F. (1992). Learning of a hippocampal dependent conditioning task changes the binding properties of AMPA receptors in rabbit hippocampus. Behav. Neural Biol. 58, 222–231.

    Article  PubMed  CAS  Google Scholar 

  42. Swanson L. W., Wyss J. M., and Cowan W. M. (1978). An autoradiographic study of the organization of intrahippocampal association pathways in the rat. J. Comp. Neurol. 181, 681–716.

    Article  PubMed  CAS  Google Scholar 

  43. Amaral D. G. and Witter M. P. (1995). Hippocampal formation: In The Rat Nervous System, Paxinos G., ed., Academic, San Diego, CA, pp. 443–493.

    Google Scholar 

  44. Ishizuka N., Weber J., and Amaral D. G. (1990). Organization of intrahippocampal projection originating from CA3 pyramidal cells in the rat. J. Comp. Neurol. 295, 580–623.

    Article  PubMed  CAS  Google Scholar 

  45. Toth K. and Freund T. F. (1992). Calbindin D28k-containing nonpyramidal cells in the rat hippocampus: their immunoreactivity for GABA and projection to the medial septum. Neuroscience 49, 793–805.

    Article  PubMed  CAS  Google Scholar 

  46. Kaibara T. and Leung L. S. (1993). Basal versus apical dendritic long-term potentiation of commissural afferents to hippocampal CA1: a current-source density study. J. Neurosci. 13, 2391–2404.

    PubMed  CAS  Google Scholar 

  47. Geinisman Y., Disterhoft J. F., Gunderson J. G., McEchron M. D., Persina I. S., Power J. M., Van der Zee E. A., and West M. J. (2000). Remodeling of hippocampal synapses after hippocampus-dependent associative learning. J. Comp. Neurol. 417, 49–59.

    Article  PubMed  CAS  Google Scholar 

  48. Geinisman Y., Berry R. W., Disterhoft J. F., Power J. M., and Van der Zee E. A. (2001). Associative learning elicits the formation of multiple synapse boutons. J. Neurosci. 21, 5568–5573.

    PubMed  CAS  Google Scholar 

  49. Kleim J. A., Freeman J. F., Bruneau R., Nolan B. C., Cooper N. R., Zook A., and Walters D. (2002). Synapse formation is associated with memory storage in the cerebellum. Proc. Natl. Acad. Sci. USA 99, 13,228–13,231.

    Article  CAS  Google Scholar 

  50. McCormick D. A. and Thompson R. F. (1984). Cerebellum: essential involvement in the classically conditioned eyelid response. Science 223, 296–299.

    Article  PubMed  CAS  Google Scholar 

  51. Knafo S., Grossman Y., Barkai E., and Benshalom G. (2001). Olfactory learning is associated with increased spine density along apical dendrites of pyramidal neurons in the rat piriform cortex. Eur. J. Neurosci. 13, 633–638.

    Article  PubMed  CAS  Google Scholar 

  52. Elston GN (2000). Pyramidal cells of the frontal lobe: all the more spinous to think with. J. Neurosci. 20, RC95.

    Google Scholar 

  53. Jacobs B., Schall M., Prather M., Kapler E., Driscoll L., Baca S., Jacobs J., Ford K., Wainwright M., and Tremi M. (2001). Regional dendritic and spine variation in human cerebral cortex: a quantitive Golgi study. Cerebral Cortex 11, 558–571.

    Article  PubMed  CAS  Google Scholar 

  54. Purpura D. P. (1974). Dendritic spine “dysgenesis” and mental retardation. Science 30, 1126–1128.

    Article  Google Scholar 

  55. Suetsugu M. and Mehraein P. (1980). Spine distribution along the apical dendrites of the pyramidal neurons in Down’s syndrome. A quantitative Golgi study. Acta. Neuropathol. (Berl.) 50, 207–210.

    Article  CAS  Google Scholar 

  56. Irwin S. A., Patel B., Idupulapati M., Harris J. B., Crisostomo R. A., Larsen B. P., Kooy F., Willems P. J., Cras P., Kozlowski P. B., Swain R. A., Weiler I. J., and Greenough W. T. (2001). Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with Fragile-X syndrome. Am. J. Med. Gen. 98, 161–167.

    Article  CAS  Google Scholar 

  57. Garey L. J., Ong W. Y., Patel T. S., Kanani M., Davis A., Mortimer A. M., Barnes T. R. E., and Hirsch S. R. (1998). Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia. J. Neurol. Neurosurg. Psychiatry 65, 446–453.

    Article  PubMed  CAS  Google Scholar 

  58. Glantz L. A. and Lewis D. A. (2000). Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch. Gen. Psychiatry 57, 65–73.

    Article  PubMed  CAS  Google Scholar 

  59. Mehraein P., Yamada M., and Tarnowska-Dziduszko E. (1975). Quantitative study on dendrites and dendritic spines in Alzheimer’s disease and senile dementia. Adv. Neurol. 12, 453–458.

    PubMed  CAS  Google Scholar 

  60. Catala I., Ferrer I., Galofre E., and Fabregues I. (1988). Decreased numbers of dendritic spines in pyramidal neurons in dementia. A quatitatove Golgi study on biopsy samples. Human Neurbiol. 6, 255–259.

    CAS  Google Scholar 

  61. Stewart M. G. and Rusakov D. A. (1995). Morphological changes associated with stages of memory formation in the chick following passive avoidance training. Behav. Brain Res. 66, 21–28.

    Article  PubMed  CAS  Google Scholar 

  62. Airey D. C., Kroodsma D. E., and DeVoogd T.J. (2000). Differences in the complexity of song tutoring cause differences in the amount learned and in dendritic spine density in a songbird telencephalic song control nucleus. Neurobiol. Learn. Mem. 73, 274–281.

    Article  PubMed  CAS  Google Scholar 

  63. Lamprecht R., and LeDoux J. (2004). Structural plasticity and memory. Nat. Rev. Neurosci. 5, 45–54.

    Article  PubMed  CAS  Google Scholar 

  64. Desmond N. L. and Levy W. B. (1997). Ovarian steroidal control of connectivity in the female hippocampus: an overview of recent experimental findings and speculations on its functional consequences. Hippocampus 7, 239–245.

    Article  PubMed  CAS  Google Scholar 

  65. Disterhoft J. F., Coulter D. A., and Alkon D. L. (1986). Conditioning-specific membrane changes of rabbit hippocampal neurons measured in vitro. Proc. Natl. Acad. Sci. USA 83, 2733–2737.

    Article  PubMed  CAS  Google Scholar 

  66. Bonhoeffer T. and Yuste R. (2002). Spine motility, phenomenology, mechanisms, and function. Neuron 35, 1019–1027.

    Article  PubMed  CAS  Google Scholar 

  67. Mizrahi A., Crowley J. C., Shtoyerman E., Katz L. C. (2004). High resolution in vivo imaging of hippocampal dendrites and spines. J. Neurosci. 24, 3147–3151.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychology, Center for Collaborative Neuroscience, Rutgers University, 08854, Piscataway, NJ

    Benedetta Leuner & Tracey J. Shors

Authors
  1. Benedetta Leuner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tracey J. Shors
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tracey J. Shors.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Leuner, B., Shors, T.J. New spines, new memories. Mol Neurobiol 29, 117–130 (2004). https://doi.org/10.1385/MN:29:2:117

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/MN:29:2:117

Index Entries

Search

Navigation