Steroidogenesis and Neuroplasticity in the Songbird Brain

  • Colin J. Saldanha
  • Barney A. Schlinger

The vertebrate brain is a source and target of steroid hormones. Songbirds have long provided an array of structural and behavioral endpoints towards understanding how steroid molecules affect neuroanatomy and neurophysiology. More recently, our conceptualization of the brain has expanded to include the CNS as a potent source of these very steroids. Here we review recent findings about the expression of steroidogenic enzymes in the songbird brain with particular emphasis upon the role of neurosteroidogenesis on the plasticity of brain circuits. We include examples of natural neuroplasticity in laboratory and field studies. Additionally, we discuss the role of neurosteroidogenesis on the outcomes of pathological brain damage. These two areas of research have provided novel and fundamentally restructured hypotheses as to the role of neurosteroidogenesis in brain function. Notable among recent findings from such studies, are the consideration of alternate substrates for steroidogenic enzymes, an expansion of the suite of enzymes found at sites of neuronal recruitment and the expression of these enzymes in additional cell types and ultrastructural compartments. The powerful link among ethology, physiology, anatomy and cell biology is exemplified in these vertebrates and renders the songbird an enduring model for the study of the role of de novo steroid synthesis on the plasticity of brain structure and function.


Testosterone estrogen neurogenesis stroke synapse 


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  1. 1.
    Berthold AA. Transplantation der Hoden. Arch Anat Physiol Wissensch Med 1849; 42–46.Google Scholar
  2. 2.
    Marler, P. Three models of song learning:evidence from behavior. J. Neurobiol 1997; 33:501–516.PubMedCrossRefGoogle Scholar
  3. 3.
    Nottebohm F, Arnold AP. Sexual dimorphism in vocal control areas of the songbird brain. Science 1976; 194:211–213.PubMedCrossRefGoogle Scholar
  4. 4.
    Brenowitz EA. Comparative approaches to the avian song system. J Neurobiol 1997; 33:517–531.PubMedCrossRefGoogle Scholar
  5. 5.
    Goodson JL, Saldanha CJ, Hahn TP, Soma KK. Recent advances in behavioral neuroendocrinology: insights from studies on birds. Horm Behav 2005; 48:461–473.PubMedCrossRefGoogle Scholar
  6. 6.
    Nottebohm F. The road we travelled: discovery, choreography, and significance of brain replaceable neurons. Ann NY Acad Sci 2004; 1016:628–658.PubMedCrossRefGoogle Scholar
  7. 7.
    Smulders TV, Sasson AD, DeVoogd TJ. Seasonal variation in hippocampal volume in a food-storing bird, the black-capped chickadee. J Neurobiol 1995; 27:15–25.PubMedCrossRefGoogle Scholar
  8. 8.
    Smulders TV, Shiflett MW, Sperling AJ, DeVoogd TJ. Seasonal changes in neuron numbers in the hippocampal formation of a food-hoarding bird: the black-capped chickadee. J Neurobiol 2000; 44:414–422.PubMedCrossRefGoogle Scholar
  9. 9.
    Sherry DF, Vaccarino AL, Buckenham K, Herz RS. The hippocampal complex of food-storing birds. Brain Behav Evol 1989; 34:308–317.PubMedCrossRefGoogle Scholar
  10. 10.
    Patel SN, Clayton NS, Krebs JR. Hippocampal tissue transplants reverse lesion-induced spatial memory deficits in zebra finches (Taeniopygia guttata). J Neurosci 1997; 17:3861–3869.PubMedGoogle Scholar
  11. 11.
    Barnea A, Nottebohm F. Recruitment and replacement of hippocampal neurons in young and adult chickadees: an addition to the theory of hippocampal learning. Proc Natl Acad Sci USA 1996; 93:714–718.PubMedCrossRefGoogle Scholar
  12. 12.
    Hoshooley JS, Sherry DF. Neuron production, neuron number, and structure size are seasonally stable in the hippocampus of the food-storing black-capped chickadee (Poecile atricapillus). Behav Neurosci 2004; 118:345–355.PubMedCrossRefGoogle Scholar
  13. 13.
    Gulledge CC, Deviche P. Autoradiographic localization of opioid receptors in vocal control regions of a male passerine bird (Junco hyemalis). J Comp Neurol 1995; 356:408–417.PubMedCrossRefGoogle Scholar
  14. 14.
    Tramontin AD, Brenowitz EA. Seasonal plasticity in the adult brain. Trends Neurosci 2000; 23:251–258.PubMedCrossRefGoogle Scholar
  15. 15.
    Tramontin AD, Wingfield JC, Brenowitz EA. Androgens and estrogens induce seasonal-like growth of song nuclei in the adult songbird brain. J Neurobiol 2003; 57:130–14016.PubMedCrossRefGoogle Scholar
  16. 16.
    Soma KK, Tramontin AD, Featherstone J, Brenowitz EA. Estrogen contributes to seasonal plasticity of the adult avian song control system. J Neurobiol 2004; 58:413–422.PubMedCrossRefGoogle Scholar
  17. 17.
    DeVoogd T, Nottebohm F. Gonadal hormones induce dendritic growth in the adult avian brain. Science 1981; 214:202–204.PubMedCrossRefGoogle Scholar
  18. 18.
    Schlinger BA, Arnold AP. Brain is the major site of estrogen synthesis in a male songbird. Proc Natl Acad Sci USA 1991; 88:4191–4194.PubMedCrossRefGoogle Scholar
  19. 19.
    Saldanha CJ, Popper P, Micevych PE, Schlinger BA. The passerine hippocampus is a site of high aromatase: inter- and intraspecies comparisons. Horm Behav 1998; 34:85–97.PubMedCrossRefGoogle Scholar
  20. 20.
    Wynne RD, Saldanha CJ. Glial aromatization decreases neural injury in the zebra finch (Taeniopygia guttata): influence on apoptosis. Journal of Neuroendocrinology 2004; 16(8): 676–683.PubMedCrossRefGoogle Scholar
  21. 21.
    Saldanha CJ, Rohmann KN, Coomaralingam L, Wynne RD. Estrogen provision by reactive glia decreases apoptosis in the zebra finch (Taeniopygia guttata). J Neurobiol 2005; 64:192–201.PubMedCrossRefGoogle Scholar
  22. 22.
    Lee DW, Fernando G, Peterson RS, Allen TA, Schlinger BA. Estrogen mediation of injury-induced cell birth in neuroproliferative regions of the adult zebra finch brain. Dev. Neurobiol. 2007; 67(8):1107–1117.PubMedCrossRefGoogle Scholar
  23. 23.
    Arvin B, Neville LF, Barone FC, Feuerstein GZ. The role of inflammation and cytokines in brain injury. Neurosci Biobehav Rev 1996; 20:445–452.PubMedCrossRefGoogle Scholar
  24. 24.
    Jorgensen MB. The role of signal transduction in the delayed necrosis of the hippocampal CA1 pyramidal cells following transient ischemia. Acta Neurol Scand Suppl 1993; 143:1–20.PubMedGoogle Scholar
  25. 25.
    Sato M, Chang E, Igarashi T, Noble LJ. Neuronal injury and loss after traumatic brain injury: time course and regional variability. Brain Res 2001; 917:45–54.PubMedCrossRefGoogle Scholar
  26. 26.
    Benkovic SA, O’Callaghan JP, Miller DB. Sensitive indicators of injury reveal hippocampal damage in C57BL/6J mice treated with kainic acid in the absence of tonic-clonic seizures. Brain Res 2004; 1024:59–76.PubMedCrossRefGoogle Scholar
  27. 27.
    Garcia-Ovejero D, Azcoitia I, Doncarlos LL, Melcangi RC, Garcia-Segura LM. Glia-neuron crosstalk in the neuroprotective mechanisms of sex steroid hormones. Brain Res Brain Res Rev 2005; 48:273–286.PubMedCrossRefGoogle Scholar
  28. 28.
    Pekny M, Nilsson M. Astrocyte activation and reactive gliosis. Glia 2005; 50:427–434.PubMedCrossRefGoogle Scholar
  29. 29.
    Wise PM, Dubal DB, Rau SW, Brown CM, Suzuki S. Are estrogens protective or risk factors in brain injury and neurodegeneration? Reevaluation after the women’s health initiative. Endocr Rev 2005; 26:308–312.PubMedCrossRefGoogle Scholar
  30. 30.
    Benkovic SA, O’Callaghan JP, Miller DB. Regional neuropathology following kainic acid intoxication in adult and aged C57BL/6J mice. Brain Res 2006; 1070:215–231.PubMedCrossRefGoogle Scholar
  31. 31.
    Liberto CM, Albrecht PJ, Herx LM, Yong VW, Levison SW. Pro-regenerative properties of cytokine-activated astrocytes. J Neurochem 2004; 89:1092–1100.PubMedCrossRefGoogle Scholar
  32. 32.
    Mrak RE, Griffin WS. Glia and their cytokines in progression of neurodegeneration. Neurobiol Aging 2005; 26:349–354.PubMedCrossRefGoogle Scholar
  33. 33.
    Peterson RS, Saldanha CJ, Schlinger BA. Rapid upregulation of aromatase mRNA and protein following neural injury in the zebra finch (Taeniopygia guttata). J Neuroendocrinol 2001; 13:317–323.PubMedCrossRefGoogle Scholar
  34. 34.
    Azcoitia I, Sierra A, Veiga S, Garcia-Segura LM. Aromatase expression by reactive astroglia is neuroprotective. Ann NY Acad Sci 2003; 1007:298–305.PubMedCrossRefGoogle Scholar
  35. 35.
    Garcia-Segura LM, Veiga S, Sierra A, Melcangi RC, Azcoitia I. Aromatase: a neuroprotective enzyme. Prog Neurobiol 2003; 71:31–41.PubMedCrossRefGoogle Scholar
  36. 36.
    Peterson RS, Lee DW, Fernando G, Schlinger BA. Radial glia express aromatase in the injured zebra finch brain. J Comp Neurol 2004; 475:261–269.PubMedCrossRefGoogle Scholar
  37. 37.
    Soma KK, Schlinger BA, Wingfield JC, Saldanha CJ. Brain aromatase, 5 alpha-reductase, and 5 beta-reductase change seasonally in wild male song sparrows: Relationship to aggressive and sexual behavior. J Neurobiol 2003; 56:209–221.PubMedCrossRefGoogle Scholar
  38. 38.
    Migeon CJ, Keller AR, Lawrence B, Shepart TH. Dehydroepiandrosterone and androsterone in human plasma: effects of age and sex: day-to-day and diurnal variations. J Clin Endocr Metab 1957; 17:1051–1062.PubMedCrossRefGoogle Scholar
  39. 39.
    Odell WD, Parker LN. Control of adrenal androgen production. Endocr Res 1984; 10:617–630.PubMedCrossRefGoogle Scholar
  40. 40.
    Labrie F, Bélanger A, Simard J, Van L-T, Labrie C. DHEA and peripheral androgen and estrogen formation: intracinology. Ann NY Acad Sci 1995; 774:16–28.PubMedCrossRefGoogle Scholar
  41. 41.
    Soma KK, Wingfield JC. Dehydroepiandrosterone in songbird plasma: seasonal regulation and relationship to territorial aggression. Gen Comp Endocrinol 2001; 123:144–155.PubMedCrossRefGoogle Scholar
  42. 42.
    Hau M, Stoddard ST, Soma KK. Territorial aggression and hormones during the non-breeding season in a tropical bird. Horm Behav 2004; 45:40–49.PubMedCrossRefGoogle Scholar
  43. 43.
    Soma KK, Wissman AM, Brenowitz EA, Wingfield JC. Dehydroepiandrosterone (DHEA) increases territorial song and the size of an associated brain region in a male songbird. Horm Behav 2002; 41:203–212.PubMedCrossRefGoogle Scholar
  44. 44.
    Alonso-Alvarez C, Bertrand S, Sorci G. Energetic reserves, leptin and testosterone: a refinement of the immunocompetence handicap hypothesis. Biol. Lett. 2007; 3(3):271–274.PubMedCrossRefGoogle Scholar
  45. 45.
    Soma KK, Tramontin AD, Wingfield JC. Oestrogen regulates male aggression in the non-breeding season. Proc R Soc Lond B Biol Sci 2000; 267:1089–1096.CrossRefGoogle Scholar
  46. 46.
    Soma KK, Sullivan KA, Tramontin AD, Saldanha CJ, Schlinger BA, Wingfield JC. Acute and chronic effects of an aromatase inhibitor on territorial aggression in breeding and nonbreeding male song sparrows. J Comp Phys A 2000; 186:759–769.CrossRefGoogle Scholar
  47. 47.
    Payne AH, Hales DB. Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones. Endocr Revs 2004; 25:947–970.CrossRefGoogle Scholar
  48. 48.
    Vanson A, Arnold AP, Schlinger BA. 3B-Hydroxysteroid dehydrogenase/Isomerase and Aromatase Activity in Primary Cultures of Developing Zebra Finch Telencephalon: Dehydroepiandrosterone as Substrate for Synthesis of Androstenedione and Estrogens. Gen Comp Endocrinol 1996; 102:342–350.PubMedCrossRefGoogle Scholar
  49. 49.
    Schlinger BA, Amur-Umarjee S, Shen P, Campagnoni AT, Arnold AP. Neuronal and non-neuronal aromatase in primary cultures of developing zebra finch telencephalon. J Neurosci 1994; 14:7541–7552.PubMedGoogle Scholar
  50. 50.
    Wade J, Schlinger BA Arnold AP. Aromatase and 5-reductase activity in cultures of developing zebra finch brain: an Investigation of sex and regional differences. J Neurobiol 1995; 27:240–251.PubMedCrossRefGoogle Scholar
  51. 51.
    London S, Monks DA, Wade J, Schlinger BA. Widespread capacity for steroid synthesis in the avian brain and song system. Endocrinology 2006; 147:5975–5987.PubMedCrossRefGoogle Scholar
  52. 52.
    Tam H, Schlinger BA. Activities of 3B-HSD and aromatase in slices of the adult and developing zebra finch brain. Gen Comp Endocrinol 2007; 150:26–33.PubMedCrossRefGoogle Scholar
  53. 53.
    Schlinger BA, Lane NI, Grisham W, Thompson L. Androgen synthesis in a songbird: a study of Cyp17 (17 alpha-hydroxylase/C17, 20-lyase) activity in the zebra finch. Gen Comp Endocrinol 1999; 113:46–58.PubMedCrossRefGoogle Scholar
  54. 54.
    Wingfield, JC Silverin B. Ecophysiological studies of hormone-behavior elations in birds. In: Pfaff DW, Arnold AP, Etgen AM, Fahrbach SE, Rubin RT (eds). Hormones, brain and behavior, Vol. 2. San Diego, CA: Academic, 2002, pp. 587–647.CrossRefGoogle Scholar
  55. 55.
    Miller WL, Achus RJ, Geller D. The regulation of 17, 20 lyase activity. Steroids 1997; 62(1):133–142.PubMedCrossRefGoogle Scholar
  56. 56.
    London S, Schlinger BA. Steroidogenic enzymes along the ventricular proliferative zone in the developing songbird brain. J Comp Neurol 2007; 502:507–521.PubMedCrossRefGoogle Scholar
  57. 57.
    London SE, Boulter J, Schlinger BA. Cloning of the zebra finch androgen synthetic enzyme CYP17: a study of its neural expression throughout posthatch development. J Comp Neurol 2003; 467:496–508.PubMedCrossRefGoogle Scholar
  58. 58.
    DeWulf V, Bottjer SW. Age and sex differences in mitotic activity within the zebra finch telencephalon. J Neurosci 2002; 22:4080–4094.PubMedGoogle Scholar
  59. 59.
    DeWulf V, Bottjer SW. Neurogenesis within the juvenile zebra finch telencephalic ventricular zone: a map of proliferative activity. J Comp Neurol 2005; 481:70–83.PubMedCrossRefGoogle Scholar
  60. 60.
    Schlinger BA. Sexual differentiation of avian brain and behavior: current views on gonadal hormone-dependent and independent mechanisms. Ann Rev Physiol 1998; 60:407–429.CrossRefGoogle Scholar
  61. 61.
    Holloway CC, Clayton DE. Estrogen synthesis in the male brain triggers development of the avian song control pathway in vitro. Nat Neurosci. 2001; 4:170–175.PubMedCrossRefGoogle Scholar
  62. 62.
    Oberlander JG, Schlinger BA, Clayton NS, Saldanha CJ. Neural aromatization accelerates the acquisition of spatial memory via an influence on the songbird hippocampus. Horm Behav 2004; 45:250–258.PubMedCrossRefGoogle Scholar
  63. 63.
    Baulieu EE. Neurosteroids: of the nervous system, by the nervous system, for the nervous system. Rec Prog Horm Res 1997; 52:1–32.PubMedGoogle Scholar
  64. 64.
    Schlinger BA, Callard GV. Localization of aromatase in synaptosomal and microsomal subfractions of quail (Coturnix coturnix japonica) brain. Neuroendocrinol 1989; 49:434–441.CrossRefGoogle Scholar
  65. 65.
    Naftolin F, Horvath TL, Jakab RL, Leranth C, Harada N, Balthazart J. Aromatase immunoreactivity in axon terminals of the vertebrate brain: an immunocytochemical study on quail, rat, monkey and human tissues. Neuroendocrinol 1996; 63:149–155.CrossRefGoogle Scholar
  66. 66.
    Peterson RS, Yarram L, Schlinger BA, Saldanha CJ. Aromatase is presynaptic and sexually-Dimorphic in the adult zebra finch brain. Proc Roy Soc Lond B 2005; 272:2089–2096.CrossRefGoogle Scholar
  67. 67.
    Rohman KN, Schlinger BA, Saldanha CJ. The subcellular compartmentalization of aromatase is sexually dimorphic in the adult zebra finch brain. Dev. Neurobiol 2006; 67:1–9.CrossRefGoogle Scholar
  68. 68.
    Gould E, Woolley CS, Frankfurt M, McEwen BS. Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood. J Neurosci 1990; 10:1286–1291.PubMedGoogle Scholar
  69. 69.
    Vockel A, Pröve E, Balthazart J. Sex- and age-related differences in the activity of testosterone-metabolizing enzymes in microdissected nuclei of the zebra finch brain. Brain Res 1990; 511:291–302.PubMedCrossRefGoogle Scholar
  70. 70.
    Schlinger BA, Amur Umarjee S, Campagnoni AT, Arnold AP. 5 beta-reductase and other androgen-metabolizing enzymes in primary cultures of developing zebra finch telencephalon. J Neuroendocrinol 1995; 7:187–192.PubMedCrossRefGoogle Scholar
  71. 71.
    Soma KK, Bindra RK, Gee J, Wingfield JC, Schlinger BA. Androgen-metabolizing enzymes show region-specific changes across the breeding season in the brain of a wild songbird. J Neurobiol 1999; 41:176–188.PubMedCrossRefGoogle Scholar
  72. 72.
    Martini L. The 5alpha-reduction of testosterone in the neuroendocrine structures. Biochemical and biophysical implications. Endocr Revs 1982; 3:1–25.CrossRefGoogle Scholar
  73. 73.
    Hutchison JB, Steimer T. Brain 5beta-reductase: a correlate of behavioral sensitivity to androgen. Science 1981; 213:244–246.PubMedCrossRefGoogle Scholar
  74. 74.
    Majewska MD. Neurosteroids: endogenous bimodal modulators of the GABAA receptor. Mechanism of action and physiological significance. Prog Neurobio 1992; 38:379–395.CrossRefGoogle Scholar
  75. 75.
    Carlisle HJ, Hales TG, Schlinger BA. Characterization of neuronal zebra finch GABA(A) receptors: steroid effects. J Comp Physiol A 1998; 182:531–538.CrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media, B.V 2008

Authors and Affiliations

  • Colin J. Saldanha
    • 1
  • Barney A. Schlinger
    • 2
  1. 1.Department of Biological SciencesLehigh UniversityBethlehemUSA
  2. 2.Department of Biological SciencesUniversity of CaliforniaLos AngelesUSA

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