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Molecular determinants mediating effects of acute stress on hippocampus-dependent synaptic plasticity and learning

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Abstract

The understanding of the molecular events underlying the neuroendocrine and behavioral sequelae of the response to stress has advanced rapidly over recent years. The hippocampus is a target of stress hormones, and we are beginning to dissect the molecular players in the modulation of synaptic plasticity and learning and memory involving this region of the brain. Given the wealth of data obtained from electrophysiological and behavioral experiments and in view of the importance to use identical experimental protocols in order to correlate the results obtained under both experimental conditions, this review focuses primarily on those contributions, which combine both approaches. From these studies it is evident that a single stressful event elicits responses in the hippocampus with different time-spans ranging from rapid changes in glutamatergic neurotransmission (i.e., N-methyl-d-aspartate receptor signaling), activation of second messenger cascades by corticotropin-releasing factor to long-lasting transcriptional changes of acetylcholinesterase. The relative contribution of these molecular targets to the stress response, the relation to hippocampal synaptic plasticity and memory formation, and the possible interaction of the underlying processes are discussed.

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References

  1. Van de Kar L. D. and Blair M. L. (1999). Forebrain pathways mediating stress-induced hormone secretion. Front. Neuroendocrinol. 20, 1–48.

    Article  PubMed  Google Scholar 

  2. McEwen B. S. (1994). Corticosteroids and hippocampal plasticity. Ann. NY Acad. Sci. USA 746, 134–142; discussion 142–144, 178–179.

    Article  CAS  Google Scholar 

  3. Huerta P. T., Sun L. D., Wilson M. A., and Tonegawa S. (2000). Formation of temporal memory requires NMDA receptors within CA1 pyramidal neurons. Neuron 25, 473–480.

    Article  PubMed  CAS  Google Scholar 

  4. Jensen O. and Lisman J. E. (2000). Position reconstruction from an ensemble of hippocampal place cells: contribution of theta phase coding. J. Neurophysiol. 83, 2602–2609.

    PubMed  CAS  Google Scholar 

  5. Phillips R. G. and LeDoux J. E. (1994). Lesions of the dorsal hippocampal formation interfere with background but not foreground contextual fear conditioning. Learn. Mem. 1, 34–44.

    PubMed  CAS  Google Scholar 

  6. Rolls E. T., Stringer S. M., and Trappenberg T. P. (2002). A unified model of spatial and episodic memory. Proc. R. Soc. Lond. B. Biol. Sci. 269, 1087–1093.

    Article  Google Scholar 

  7. Wilson M. A. and McNaughton B. L. (1993). Dynamics of the hippocampal ensemble code for space. Science 261, 1055–1058.

    Article  PubMed  CAS  Google Scholar 

  8. Kim J. J. and Diamond D. M. (2002). The stressed hippocampus, synaptic plasticity and lost memories. Nat. Rev. Neurosci. 3, 453–462.

    Article  PubMed  CAS  Google Scholar 

  9. Diamond D. M., Fleshner M., Ingersoll N., and Rose G. M. (1996). Psychological stress impairs spatial working memory: relevance to electrophysiological studies of hippocampal function. Behav. Neurosci. 110, 661–672.

    Article  PubMed  CAS  Google Scholar 

  10. Diamond D. M., Park C. R., Heman K. L., and Rose G. M. (1999). Exposing rats to a predator impairs spatial working memory in the radial arm water maze. Hippocampus 9, 542–552.

    Article  PubMed  CAS  Google Scholar 

  11. Baker K. B. and Kim J. J. (2002). Effects of stress and hippocampal NMDA receptor antagonism on recognition memory in rats. Learn. Mem. 9, 58–65.

    Article  PubMed  Google Scholar 

  12. Clark R. E., Zola S. M., and Squire L. R. (2000). Impaired recognition memory in rats after damage to the hippocampus. J. Neurosci. 20, 8853–8860.

    PubMed  CAS  Google Scholar 

  13. Nadel L. (1991). Is the hippocampal formation preferentially involved in spatial behavior? Hippocampus 1, 221–292.

    Article  PubMed  CAS  Google Scholar 

  14. Blank T., Nijholt I., Eckart K., and Spiess J. (2002). Priming of long-term potentiation in mouse hippocampus by corticotropin-releasing factor and acute stress: implications for hippocampus-dependent learning. J. Neurosci. 22, 3788–3794.

    PubMed  CAS  Google Scholar 

  15. Radulovic J., Ruhmann A., Liepold T., and Spiess J. (1999). Modulation of learning and anxiety by corticotropin-releasing factor (CRF) and stress: differential roles of CRF receptors 1 and 2. J. Neurosci. 19, 5016–5025.

    PubMed  CAS  Google Scholar 

  16. Beylin A. V. and Shors T. J. (1998). Stress enhances excitatory trace eyeblink conditioning and opposes acquisition of inhibitory conditioning. Behav. Neurosci. 112, 1327–1338.

    Article  PubMed  CAS  Google Scholar 

  17. Foy M. R., Stanton M. E., Levine S., and Thompson R. F. (1987). Behavioral stress impairs long-term potentiation in rodent hippocampus. Behav. Neural. Biol. 48, 138–149.

    Article  PubMed  CAS  Google Scholar 

  18. Garcia R., Musleh W., Tocco G., Thompson R. F., and Baudry M. (1997). Time-dependent blockade of STP and LTP in hippocampal slices following acute stress. Neurosci. Lett. 233, 41–44.

    Article  PubMed  CAS  Google Scholar 

  19. McNaughton N. and Morris R. G. (1987). Chlordiazepoxide, an anxiolytic benzodiazepine, impairs place navigation in rats. Behav. Brain Res. 24, 39–46.

    Article  PubMed  CAS  Google Scholar 

  20. Bliss T. V. and Collingridge G. L. (1993). A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361, 31–39.

    Article  PubMed  CAS  Google Scholar 

  21. Mesches M. H., Fleshner M., Heman K. L., Rose G. M., and Diamond D. M. (1999). Exposing rats to a predator blocks primed burst potentiation in the hippocampus in vitro. J. Neurosci. 19, RC18: 1–5.

    Google Scholar 

  22. Diamond D. M. and Rose G. M. (1994). Stress impairs LTP and hippocampal-dependent memory. Ann. NY Acad. Sci. 746, 411–414.

    Article  PubMed  CAS  Google Scholar 

  23. Xu L., Anwyl R., and Rowan M. J. (1997). Behavioural stress facilitates the induction of long-term depression in the hippocampus. Nature 387, 497–500.

    Article  PubMed  CAS  Google Scholar 

  24. Lowy M. T., Gault L., and Yamammoto B. K. (1993). Adrenalectomy attenuates stress-induced elevations in extracellular glutamate concentrations in the hippocampus. J. Neurochem. 61, 1957–1960.

    Article  PubMed  CAS  Google Scholar 

  25. Moghaddam G. (1993). Stress preferentially increases extraneuronal levels of excitatory amino acids in the prefrontal cortex: Comparison to hippocampus and basal ganglia. J. Neurochem. 60, 1650–1657.

    Article  PubMed  CAS  Google Scholar 

  26. Bartanusz V., Aubry J. M., Pagliusi S., Jezova D., Baffi J., and Kiss J. Z. (1995). Stress-induced changes in messenger RNA levels of N-methyl-d-aspartate and AMPA receptor subunits in selected regions of the rat hippocampus and hypothalamus. Neuroscience 66, 247–252.

    Article  PubMed  CAS  Google Scholar 

  27. Kim J. J., Foy M. R., and Thompson R. F. (1996). Behavioral stress modifies hippocampal plasticity through N-methyl-d-aspartate receptor activation. Proc. Natl. Acad. Sci. USA 93, 4750–4753.

    Article  PubMed  CAS  Google Scholar 

  28. Ennaceur A. and Delacour J. (1988). A new one-trial test for neurobiological studies of memory in rats. 1. Behavioral data. Behav. Brain Res. 31, 47–59.

    Article  PubMed  CAS  Google Scholar 

  29. Clark R. E., Zola S. M., and Squire L. R. (2000). Impaired recognition memory in rats after damage to the hippocampus. J. Neurosci. 20, 8853–8860.

    PubMed  CAS  Google Scholar 

  30. Spiess J., Rivier J., Rivier C., and Vale W. (1981). Primary structure of corticotropin-releasing factor from ovine hypothalamus. Proc. Natl. Acad. Sci. USA 78, 6517–6521.

    Article  PubMed  CAS  Google Scholar 

  31. Imaki T., Katsumata H., Miyata M., Naruse M., Imaki J., and Minami S. (2001). Expression of corticotropin-releasing hormone type 1 receptor in paraventricular nucleus after acute stress. Neuroendocrinology 73, 293–301.

    Article  PubMed  CAS  Google Scholar 

  32. Merchenthaler I. (1984). Corticotropin releasing factor (CRF)-like immunoreactivity in the rat central nervous system. Extrahypothalamic distribution. Peptides 5, 53–69.

    Article  PubMed  CAS  Google Scholar 

  33. Swanson L. W., Sawchenko P. E., Rivier J., and Vale W. W. (1983). Organization of ovine corticotropin-releasing factor immunoreactive cells and fibers in the rat brain: an immunohistochemical study. Neuroendocrinology 36, 165–186.

    PubMed  CAS  Google Scholar 

  34. Aldenhoff J. B., Gruol D. L., Rivier J., Vale W., and Siggins G. R. (1983). Corticotropin releasing factor decreases postburst hyperpolarizations and excites hippocampal neurons. Science 221, 875–877.

    Article  PubMed  CAS  Google Scholar 

  35. Haug T. and Storm J. F. (2000). Protein kinase A mediates the modulation of the slow Ca(2+)-dependent K(+) current, I(sAHP), by the neuropeptides CRF, VIP, and CGRP in hippocampal pyramidal neurons. J. Neurophysiol. 83, 2071–2079.

    PubMed  CAS  Google Scholar 

  36. Blank T., Nijholt I., Grammatopoulos D. K., Randeva H. S., Hillhouse E. W., and Spiess J. (2003). Corticotropin-releasing factor receptors couple to multiple G-proteins to activate diverse intracellular signaling pathways in mouse hippocampus: role in neuronal excitability and associative learning. J. Neurosci. 23, 700–707.

    PubMed  CAS  Google Scholar 

  37. Hollrigel G. S., Chen K., Baram T. Z., and Soltesz I. (1998). The pro-convulsant actions of corticotropin-releasing hormone in the hippocampus of infant rats. Neuroscience 84, 71–79.

    Article  PubMed  CAS  Google Scholar 

  38. Wang H. L., Tsai L. Y., and Lee E. H. (2000). Corticotropin-releasing factor produces a protein synthesis-dependent long-lasting potentiation in dentate gyrus neurons. J. Neurophysiol. 83, 343–349.

    PubMed  CAS  Google Scholar 

  39. Wang H. L., Wayner M. J., Chai C. Y., and Lee E. H. (1998). Corticotrophin-releasing factor produces a long-lasting enhancement of synaptic efficacy in the hippocampus. Eur. J. Neurosci. 10, 3428–3437.

    Article  PubMed  CAS  Google Scholar 

  40. Contarino A., Dellu F., Koob G. F., Smith G. W., Lee K. F., Vale W., and Gold L. H. (1999). Reduced anxiety-like and cognitive performance in mice lacking the corticotropin-releasing factor receptor 1. Brain Res. 835, 1–9.

    Article  PubMed  CAS  Google Scholar 

  41. Vaughan J., Donaldson C., Bittencourt J., et al. (1995). Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor. Nature 378, 287–292.

    Article  PubMed  CAS  Google Scholar 

  42. Zorrilla E. P., Schulteis G., Ormsby A., Klaassen A., Ling N., McCarthy J. R., Koob G. F., and De Souza E. B. (2002). Urocortin shares the memory modulating effects of corticotropin-releasing factor (CRF): mediation by CRF1 receptors. Brain Res. 952, 200–210.

    Article  PubMed  CAS  Google Scholar 

  43. Imperato A., Puglisi-Allegra S., Casolini P., and Angelucci L. (1991). Changes in brain dopamine and acetylcholine release during and following stress are independent of the pituitary-adrenocortical axis. Brain Res. 538, 111–117.

    Article  PubMed  CAS  Google Scholar 

  44. Kaufer D., Friedman A., Seidman S., and Soreq H. (1998). Acute stress facilitates long-lasting changes in cholinergic gene expression. Nature 393, 373–377.

    Article  PubMed  CAS  Google Scholar 

  45. Behra M., Cousin X., Bertrand C., Vonesch J. L., Biellmann D., Chatonnet A., and Strahle U. (2002). Acetylcholinesterase is required for neuronal and muscular development in the zebrafish embryo. Nat. Neurosci. 5, 111–118.

    Article  PubMed  CAS  Google Scholar 

  46. Massoulie J. (2002). The origin of the molecular diversity and functional anchoring of cholinesterases. Neurosignals 11, 130–143.

    Article  PubMed  CAS  Google Scholar 

  47. Birikh K., Sklan E., Shoham S., and Soreq H. (2003). Interaction of “Readthrough” acetylcholinesterase with RACK1 and PKCβII correlates with intensified fear induced conflict behavior. Proc. Natl. Acad. Sci. USA 100, 283–288.

    Article  PubMed  CAS  Google Scholar 

  48. Meshorer E., Erb C., Gazit R., et al. (2002). Alternative splicing and neuritic mRNA translocation under long-term neuronal hypersensitivity. Science 295, 508–512.

    Article  PubMed  CAS  Google Scholar 

  49. Soreq H. and Seidman S. (2001). Acetylcholinesterase—new roles for an old actor. Nat. Rev. Neurosci. 2, 294–302.

    Article  PubMed  CAS  Google Scholar 

  50. Nijholt I., Farchi N., Kye M. (2004). Stress-induced alternative splicing of acetylcholinesterase results in enhanced fear memory and long-term potentiation. Mol. Psychiatry 9, 174–183.

    Article  PubMed  CAS  Google Scholar 

  51. Beeri R., Andres C., Lev-Lehman E., Timberg R., Huberman T., Shani M., and Soreq H. (1995). Transgenic expression of human acetylcholinesterase induces progressive cognitive deterioration in mice. Curr. Biol. 5, 1063–1071.

    Article  PubMed  CAS  Google Scholar 

  52. Beeri R., Le Novere N., Mervis R., Huberman T., Grauer E., Changeux J. P., and Soreq H. (1997). Enhanced hemicholinium binding and attenuated dendrite branching in cognitively impaired acetylcholinesterase-transgenic mice. J. Neurochem. 69, 2441–2451.

    Article  PubMed  CAS  Google Scholar 

  53. Morris R. G., Garrud P., Rawlins J. N., and O’Keefe J. (1982). Place navigation impaired in rats with hippocampal lesions. Nature 297, 681–683.

    Article  PubMed  CAS  Google Scholar 

  54. Moser E., Moser M. B., and Andersen P. (1993). Spatial learning impairment parallels the magnitude of dorsal hippocampal lesions, but is hardly present following ventral lesions. J. Neurosci. 13, 3916–3925.

    PubMed  CAS  Google Scholar 

  55. Erb C., Troost J., Kopf S., Schmitt U., Loffelholz K., Soreq H., and Klein J. (2001). Compensatory mechanisms enhance hippocampal acetylcholine release in transgenic mice expressing human acetylcholinesterase. J. Neurochem. 77, 638–646.

    Article  PubMed  CAS  Google Scholar 

  56. Cohen O., Erb C., Ginzberg D., Pollak Y., Seidman S., Shoham S., Yirmiya R., and Soreq H. (2002). Overexpression of “readthrough” acetylcholinesterase is associated with antisense suppressible behavioral impairments. Mol. Psychiatry 7, 874–885.

    Article  PubMed  CAS  Google Scholar 

  57. Weeber E. J., Atkins C. M., Selcher J. C., et al. (2000). A role for the beta isoform of protein kinase C in fear conditioning. J. Neurosci. 20, 5906–5914.

    PubMed  CAS  Google Scholar 

  58. Shors T. J., Weiss C., and Thompson R. F. (1992). Stress-induced facilitation of classical conditioning. Science 257, 537–539.

    Article  PubMed  CAS  Google Scholar 

  59. Bortolotto Z. A., Bashir Z. I., Davies C. H., and Collingridge G. L. (1994). A molecular switch activated by metabotropic glutamate receptors regulates induction of long-term potentiation. Nature 368, 740–743.

    Article  PubMed  CAS  Google Scholar 

  60. Christie B. R., Stellwagen D., and Abraham W. C. (1995). Evidence for common expression mechanisms underlying heterosynaptic and associative long-term depression in the dentate gyrus. J. Neurophysiol. 74, 1244–1247.

    PubMed  CAS  Google Scholar 

  61. Cohen A. S. and Abraham W. C. (1996). Facilitation of long-term potentiation by prior activation of metabotropic glutamate receptors. J. Neurophysiol. 76, 953–962.

    PubMed  CAS  Google Scholar 

  62. Cohen A. S., Coussens C. M., Raymond C. R., and Abraham W. C. (1999). Long-lasting increase in cellular excitability associated with the priming of LTP induction in rat hippocampus. J. Neurophysiol. 82, 3139–3148.

    PubMed  CAS  Google Scholar 

  63. Cohen A. S., Raymond C. R., and Abraham W. C. (1998). Priming of long-term potentiation induced by activation of metabotropic glutamate receptors coupled to phospholipase C. Hippocampus 8, 160–170.

    Article  PubMed  CAS  Google Scholar 

  64. Raymond C. R., Thompson V. L., Tate W. P., and Abraham W. C. (2000). Metabotropic glutamate receptors trigger homosynaptic protein synthesis to prolong long-term potentiation. J. Neurosci. 20, 969–976.

    PubMed  CAS  Google Scholar 

  65. Aniksztejn L., Otani S., and Ben-Ari Y. (1992). Quisqualate metabotropic receptors modulate NMDA currents and facilitate induction of long-term potentiation through protein kinase C. Eur. J. Neurosci. 4, 500–505.

    Article  PubMed  Google Scholar 

  66. Challis R. A., Mistry R., Gray D. W., and Nahorski S. R. (1994). Modulation of muscarinic cholinoceptor-stimulated inositol 1,4,5-trisphosphate accumulation by N-methyl-d-aspartate in neonatal rat cerebral cortex. Neuropharmacology 33, 15–25.

    Article  PubMed  CAS  Google Scholar 

  67. Harvey J. and Collingridge G. L. (1993). Signal transduction pathways involved in the acute potentiation of NMDA responses by 1S,3R-ACPD in rat hippocampal slices. Br. J. Pharmacol. 109, 1085–1090.

    PubMed  CAS  Google Scholar 

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  1. Department of Molecular Neuroendocrinology, Max Planck Institute for Experimental Medicine, D-37075, Goettingen, Germany

    Thomas Blank, Ingrid Nijholt & Joachim Spiess

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  1. Thomas Blank
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Correspondence to Thomas Blank.

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Blank, T., Nijholt, I. & Spiess, J. Molecular determinants mediating effects of acute stress on hippocampus-dependent synaptic plasticity and learning. Mol Neurobiol 29, 131–138 (2004). https://doi.org/10.1385/MN:29:2:131

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