Estradiol; Neurogenesis; Sex difference; Singing behavior; Song analysis; Song control system; Songbirds; Testosterone; Endocrinology; Endocrine and Autonomic Systems; Behavioral Neuroscience
Abstract :
[en] Adult treatments with testosterone (T) do not activate singing behavior nor promote growth of song control nuclei to the same extent in male and female canaries (Serinus canaria). Because T acts in part via aromatization into an estrogen and brain aromatase activity is lower in females than in males in many vertebrates, we hypothesized that this enzymatic difference might explain the sex differences seen even after exposure to the same amount of T. Three groups of castrated males and 3 groups of photoregressed females (i.e., with quiescent ovaries following exposure to short days) received either 2 empty 10 mm silastic implants, one empty implant and one implant filled with T or one implant filled with T plus one with estradiol (E2). Songs were recorded for 3 h each week for 6 weeks before brains were collected and song control nuclei volumes were measured in Nissl-stained sections. Multiple measures of song were still different in males and females following treatment with T. Co-administration of E2 did not improve these measures and even tended to inhibit some measures such as song rate and song duration. The volume of forebrain song control nuclei (HVC, RA, Area X) and the rate of neurogenesis in HVC was increased by the two steroid treatments, but remained significantly smaller in females than in males irrespective of the endocrine condition. These sex differences are thus not caused by a lower aromatization of the steroid; sex differences in canaries are probably organized either by early steroid action or by sex-specific gene regulation directly in the brain.
Disciplines :
Neurosciences & behavior
Author, co-author :
Dos Santos, Ednei Barros; Laboratory of Behavioral Neuroendocrinology, GIGA Neurosciences, University of Liege, Belgium
Ball, Gregory F; Department of Psychology, University of Maryland, College Park, MD, USA
Cornil, Charlotte ; Université de Liège - ULiège > GIGA > GIGA Neurosciences - Neuroendocrinology
Balthazart, Jacques ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Language :
English
Title :
Treatment with androgens plus estrogens cannot reverse sex differences in song and the song control nuclei in adult canaries.
NINDS - National Institute of Neurological Disorders and Stroke
Funding text :
This work was supported by a Grant from the National Institute of Neurological Disorders and Stroke Grant RO1NS104008 (to G.F.B., J.B., and C.A.C.). We thank Pr. Robert Dooling and Ed. Smith, Department of Psychology, University of Maryland in College Park for providing the MATLAB script used to analyze canary song. C.A.C. is F.R.S.-FNRS Research Director.
Alvarez-Borda, B., Nottebohm, F., Gonads and singing play separate, additive roles in new neuron recruitment in adult canary brain. J. Neurosci. 22 (2002), 8684–8690.
Alvarez-Buylla, A., Kirn, J.R., Birth, migration, incorporation, and death of vocal control neurons in adult songbirds. J. Neurobiol. 33 (1997), 585–601.
Alward, B.A., Balthazart, J., Ball, G.F., Differential effects of global versus local testosterone on singing behavior and its underlying neural substrate. Proc. Natl. Acad. Sci. U. S. A. 110 (2013), 19573–19578.
Alward, B.A., Balthazart, J., Ball, G.F., Dissociable effects on birdsong of androgen signaling in cortex-like brain regions of canaries. J. Neurosci. 37 (2017), 8612–8624.
Alward, B.A., de Bournonville, C., Chan, T.T., Balthazart, J., Cornil, C.A., Ball, G.F., Aromatase inhibition rapidly affects in a reversible manner distinct features of birdsong. Sci. Rep., 6, 2016, 32344.
Alward, B.A., Madison, F.N., Gravley, W.T., Ball, G.F., Antagonism of syringeal androgen receptors reduces the quality of female-preferred male song in canaries. Anim. Behav. 119 (2016), 201–212.
Alward, B.A., Madison, F.N., Parker, S.E., Balthazart, J., Ball, G.F., Pleiotropic control by testosterone of a learned vocal behavior and its underlying neuroplasticity (1,2,3). eNeuro, 3, 2016.
Appeltants, D., Ball, G.F., Balthazart, J., Song activation by testosterone is associated with an increased catecholaminergic innervation of the song control system in female canaries. Neuroscience 121 (2003), 801–814.
Ball, G.F., Balthazart, J., The neuroendocrinology and neurochemistry of birdsong. Handbook of Neurochemistry And Molecular Neurobiology: Behavioral Neurochemistry, Neuroendocrinology And Molecular Neurobiology, 2007, 419–457.
Balthazart, J., Ball, G.F., Endogenous versus exogenous markers of adult neurogenesis in canaries and other birds: advantages and disadvantages. J. Comp. Neurol. 522 (2014), 4100–4120.
Balthazart, J., Ball, G.F., Endocrine and social regulation of adult neurogenesis in songbirds. Front. Neuroendocrinol. 41 (2016), 3–22.
Balthazart, J., Boseret, G., Konkle, A.T., Hurley, L.L., Ball, G.F., Doublecortin as a marker of adult neuroplasticity in the canary song control nucleus HVC. Eur. J. Neurosci. 27 (2008), 801–817.
Balthazart, J., Hirschberg, D., Differential release of various androgens from silastic implants. I.R.C.S. Med. Sci., 7, 1979 123-120.
Barker, J.M., Ball, G.F., Balthazart, J., Anatomically discrete sex differences and enhancement by testosterone of cell proliferation in the telencephalic ventricle zone of the adult canary brain. J. Chem. Neuroanat. 55 (2014), 1–8.
Bernard, D.J., Bentley, G.E., Balthazart, J., Turek, F.W., Ball, G.F., Androgen receptor, estrogen receptor alpha, and estrogen receptor beta show distinct patterns of expression in forebrain song control nuclei of European starlings. Endocrinology 140 (1999), 4633–4643.
Boseret, G., Ball, G.F., Balthazart, J., The microtubule-associated protein doublecortin is broadly expressed in the telencephalon of adult canaries. J. Chem. Neuroanat. 33 (2007), 140–154.
Bottjer, S.W., Johnson, F., Circuits, hormones, and learning: vocal behavior in songbirds. J. Neurobiol. 33 (1997), 602–618.
Brainard, M.S., Contributions of the anterior forebrain pathway to vocal plasticity. Ann. N. Y. Acad. Sci. 1016 (2004), 377–394.
Brainard, M.S., Doupe, A.J., What songbirds teach us about learning. Nature 417 (2002), 351–358.
Brenowitz, E.A., Larson, T.A., Neurogenesis in the adult avian song-control system. Cold Spring Harb. Perspect. Biol., 7, 2015, a019000.
Callard, G.V., Petro, Z., Ryan, K.J., Phylogenetic distribution of aromatase and other androgen-converting enzymes in the central nervous system. Endocrinology 103 (1978), 2283–2290.
Cornez, G., Collignon, C., Muller, W., Cornil, C.A., Ball, G.F., Balthazart, J., Development of perineuronal nets during ontogeny correlates with sensorimotor vocal learning in canaries. eNeuro, 7, 2020.
Cornez, G., Shevchouk, O.T., Ghorbanpoor, S., Ball, G.F., Cornil, C.A., Balthazart, J., Testosterone stimulates perineuronal nets development around parvalbumin cells in the adult canary brain in parallel with song crystallization. Horm. Behav., 119, 2020, 104643.
Cornez, G., Valle, S., Dos Santos, E.B., Chiver, I., Muller, W., Ball, G.F., Cornil, C.A., Balthazart, J., Perineuronal nets in HVC and plasticity in male canary song. PloS one, 16, 2021, e0252560.
Francis, F., Koulakoff, A., Boucher, D., Chafey, P., Schaar, B., Vinet, M.C., Friocourt, G., McDonnell, N., Reiner, O., Kahn, A., McConnell, S.K., Berwald-Netter, Y., Denoulet, P., Chelly, J., Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons. Neuron 23 (1999), 247–256.
Fusani, L., Gahr, M., Hormonal influence on song structure and organization: the role of estrogen. Neuroscience 138 (2006), 939–946.
Fusani, L., Metzdorf, R., Hutchison, J.B., Gahr, M., Aromatase inhibition affects testosterone-induced masculinization of song and the neural song system in female canaries. J. Neurobiol. 54 (2003), 370–379.
Gahr, M., Güttinger, H.-R., Kroodsma, D.E., Estrogen receptors in the avian brain: survey reveals general distribution and forebrain areas unique to songbirds. J. Comp. Neurol. 327 (1993), 112–122.
Goldman, S.A., Nottebohm, F., Neuronal production, migration, and differentiation in a vocal control nucleus of the adult female canary brain. Proc. Natl. Acad. Sci. U. S. A. 80 (1983), 2390–2394.
Griffiths, R., Double, M.C., Orr, K., Dawson, R.J., A DNA test to sex most birds. Mol. Ecol. 7 (1998), 1071–1075.
Harding, C.F., Hormonal modulation of singing behavior: methodology and principles of hormone action. Zeigler, H.P., Marler, P., (eds.) Neuroscience of Birdsong, 2008, Cambridge University Press, Cambridge, 305–319.
Hartog, T.E., Dittrich, F., Pieneman, A.W., Jansen, R.F., Frankl-Vilches, C., Lessmann, V., Lilliehook, C., Goldman, S.A., Gahr, M., Brain-derived neurotrophic factor signaling in the HVC is required for testosterone-induced song of female canaries. J. Neurosci. 29 (2009), 15511–15519.
Hutchison, J.B., Beyer, C., Green, S., Wozniak, A., Brain formation of oestrogen in the mouse: sex dimorphism in aromatase development. J. Steroid Biochem. Mol. Biol. 49 (1994), 407–415.
Ko, M.C., Frankl-Vilches, C., Bakker, A., Gahr, M., The gene expression profile of the song control nucleus HVC shows sex specificity, hormone responsiveness, and species specificity among songbirds. Front. Neurosci., 15, 2021, 680530.
Leboucher, G., Kreutzer, M., Dittami, J., Copulation-solicitation displays in female canaries (Serinus canaria): are oestradiol implants necessary?. Ethology 97 (1994), 190–197.
Li, X.C., Jarvis, E.D., Alvarez-Borda, B., Lim, D.A., Nottebohm, F., A relationship between behavior, neurotrophin expression, and new neuron survival. PNAS 97 (2000), 8584–8589.
Lieberburg, I., Nottebohm, F., High-affinity androgen binding proteins in synrigeal tissues of songbirds. Gen. Comp. Endocrinol. 37 (1979), 286–293.
Liere, P., Cornil, C.A., de Bournonville, M.P., Pianos, A., Keller, M., Schumacher, M., Balthazart, J., Steroid profiles in quail brain and serum: sex and regional differences and effects of castration with steroid replacement. J. Neuroendocrinol., 31, 2019, e12681.
Louissaint, A.J., Rao, S., Leventhal, C., Goldman, S.A., Coordinated interaction of neurogenesis and angiogenesis in the adult songbird brain. Neuron 34 (2002), 945–960.
Madison, F.N., Haakenson, C.M., Whitaker, A.R., Kawiiso, A.M., Ball, G.F., Intrinsic sex differences in steroid hormone-modulated neuroplasticity in canaries (Serinus canaria). Abstracts Soc. Neurosci., 2019, 233.25/Q238.
Madison, F.N., Rouse, M.L. Jr., Balthazart, J., Ball, G.F., Reversing song behavior phenotype: testosterone driven induction of singing and measures of song quality in adult male and female canaries (Serinus canaria). Gen. Comp. Endocrinol. 215 (2015), 61–75.
Metzdorf, R., Gahr, M., Fusani, L., Distribution of aromatase, estrogen receptor, and androgen receptor mRNA in the forebrain of songbirds and nonsongbirds. J. Comp. Neurol. 407 (1999), 115–129.
Mooney, R., Neural mechanisms for learned birdsong. Learn. Mem. 16 (2009), 655–669.
Nottebohm, F., Testosterone triggers growth of brain vocal control nuclei in adult female canaries. Brain Res. 189 (1980), 429–436.
Nottebohm, F., A brain for all seasons: cyclical anatomical changes in song-control nuclei of the canary brain. Science 214 (1981), 1368–1370.
Nottebohm, F., Arnold, A.P., Sexual dimorphism in vocal control areas of the songbird brain. Science 194 (1976), 211–213.
Nottebohm, F., Stokes, T.M., Leonard, C.M., Central control of song in the canary, Serinus canarius. J. Comp. Neurol. 165 (1976), 457–486.
Pytte, C., Wilbrecht, L., Kirn, J.R., Regulation an function of neuronal replacement in the avian song system. Zeigler, H.P., Marler, P., (eds.) Neuroscience of Birdsong, 2008, Cambridge University Press, Cambridge, 350–366.
Rasika, S., Nottebohm, F., Alvarez-Buylla, A., Testosterone increases the recruitment and/or survival of new high vocal center neurons in adult female canaries. Proc. Natl. Acad. Sci. U. S. A. 91 (1994), 7854–7858.
Roselli, C., The distribution and regulation of aromatase in the mammalian brain: from mice to monkeys. Balthazart, J., Ball, G.F., (eds.) Brain Aromatase, Estrogens, And Behavior, 2013, Oxford University Press, Oxford, New York, 43–63.
Roselli, C.E., Sex differences in androgen receptors and aromatase activity in microdissected regions of the rat brain. Endocrinology 128 (1991), 1310–1316.
Roselli, C.E., Resko, J.A., Aromatase activity in the rat brain: hormonal regulation and sex differences. J. Steroid Biochem. Mol. Biol. 44 (1993), 499–508.
Sartor, J.J., Balthazart, J., Ball, G.F., Coordinated and dissociated effects of testosterone on singing behavior and song control nuclei in canaries (Serinus canaria). Horm. Behav. 47 (2005), 467–476.
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., Tinevez, J.Y., White, D.J., Hartenstein, V., Eliceiri, K., Tomancak, P., Cardona, A., Fiji: an open-source platform for biological-image analysis. Nat. Methods 9 (2012), 676–682.
Schlinger, B.A., Sex steroids and their actions on the birdsong system. J. Neurobiol. 33 (1997), 619–631.
Schlinger, B.A., Brenowitz, E.A., Neural and hormonal control of birdsong. Pfaff, D.W., Joels, M., (eds.) Hormones, Brain And Behavior, 3rd ed., 2017, Academic Press, Oxford, 255–290.
Schumacher, M., Balthazart, J., Sexual dimorphism of the hypothalamic metabolism of testosterone in the Japanese quail (Coturnix coturnix japonica). Prog. Brain Res. 61 (1984), 53–61.
Schumacher, M., Balthazart, J., Testosterone-induced brain aromatase is sexually dimorphic. Brain Res. 370 (1986), 285–293.
Shevchouk, O.T., Ball, G.F., Cornil, C.A., Balthazart, J., Studies of HVC plasticity in adult canaries reveal social effects and sex differences as well as limitations of multiple markers available to assess adult neurogenesis. PloS one, 12, 2017, e0170938.
Shevchouk, O.T., Ball, G.F., Cornil, C.A., Balthazart, J., Rapid testosterone-induced growth of the medial preoptic nucleus in male canaries. Physiol. Behav. 204 (2019), 20–26.
Shevchouk, O.T., Ghorbanpoor, S., Ball, G.F., Cornil, C.A., Balthazart, J., Testosterone-induced neuroendocrine changes in the medial preoptic area precede song activation and plasticity in song control nuclei of female canaries. Eur. J. Neurosci. 45 (2017), 886–900.
Shevchouk, O.T., Ghorbanpoor, S., Smith, E., Liere, P., Schumacher, M., Ball, G.F., Cornil, C.A., Balthazart, J., Behavioral evidence for sex steroids hypersensitivity in castrated male canaries. Horm. Behav. 103 (2018), 80–96.
Soma, K.K., Tramontin, A.D., Featherstone, J., Brenowitz, E.A., Estrogen contributes to seasonal plasticity of the adult avian song control system. J. Neurobiol. 58 (2004), 413–422.
Tramontin, A.D., Wingfield, J.C., Brenowitz, E.A., Androgens and estrogens induce seasonal-like growth of song nuclei in the adult songbird brain. J. Neurobiol. 57 (2003), 130–140.
Vandries, L.M., Ghorbanpoor, S., Cornez, G., Shevchouk, O.T., Ball, G.F., Cornil, C.A., Balthazart, J., Testosterone or estradiol when implanted in the medial preoptic nucleus trigger short low-amplitude songs in female canaries. eNeuro, 6, 2019.
Veney, S.L., Wade, J., Steroid receptors in the adult zebra finch syrinx: a sex difference in androgen receptor mRNA, minimal expression of estrogen receptor alpha and aromatase. Gen. Comp. Endocrinol. 136 (2004), 192–199.
Veney, S.L., Wade, J., Post-hatching syrinx development in the zebra finch: an analysis of androgen receptor, aromatase, estrogen receptor alpha and estrogen receptor beta mRNAs. J. Comp. Physiol. A Neuroethol. Sens. Neural Behav. Physiol. 191 (2005), 97–104.
Yamamura, T., Barker, J.M., Balthazart, J., Ball, G.F., Androgens and estrogens synergistically regulate the expression of doublecortin and enhance neuronal recruitment in the song system of adult female canaries. J. Neurosci. 31 (2011), 9649–9657.
