To modulate and be modulated: estrogenic influences on auditory processing of communication signals within a socio-neuro-endocrine framework

Abstract

Gonadal hormones modulate behavioral responses to sexual stimuli, and communication signals can also modulate circulating hormone levels. In several species, these combined effects appear to underlie a two-way interaction between circulating gonadal hormones and behavioral responses to socially salient stimuli. Recent work in songbirds has shown that manipulating local estradiol levels in the auditory forebrain produces physiological changes that affect discrimination of conspecific vocalizations and can affect behavior. These studies provide new evidence that estrogens can directly alter auditory processing and indirectly alter the behavioral response to a stimulus. These studies show that: 1) Local estradiol action within an auditory area is necessary for socially relevant sounds to induce normal physiological responses in the brains of both sexes; 2) These physiological effects occur much more quickly than predicted by the classical time-frame for genomic effects; 3) Estradiol action within the auditory forebrain enables behavioral discrimination among socially relevant sounds in males; and 4) Estradiol is produced locally in the male brain during exposure to particular social interactions. The accumulating evidence suggests a socio-neuro-endocrinology framework in which estradiol is essential to auditory processing, is increased by a socially relevant stimulus, acts rapidly to shape perception of subsequent stimuli experienced during social interactions, and modulates behavioral responses to these stimuli. Brain estrogens are likely to function similarly in both songbird sexes because aromatase and estrogen receptors are present in both male and female forebrain. Estrogenic modulation of perception in songbirds and perhaps other animals could fine-tune male advertising signals and female ability to discriminate them, facilitating mate selection by modulating behaviors.

Figure 1

Ascending auditory relays within the Avian Brain. Sound information from the peripheral cochlea is transmitted to the cochlear nucleus (CN) within the brainstem and on to MLd, the homolog of mammalian inferior colliculus. Projections from MLd then enter the thalamic Nucleus Ovoidalis (Ov; homolog of mammalian Medial geniculate nucleus). In mammals, these thalamic neurons project to the layered auditory cortex. In the avian system, they project first to the areas of Field L, which sends projections to both NCM and CMM (yellow). Figure from Bolhuis et al, 2010. Reprinted with permission from MacMillan Publishers Ltd: Nature Reviews Neuroscience (11), copyright 2010.

Figure 2

Figures 2a and 2b. (a) Multiunit NCM response strength differs when an animal hears playback of different sound types. Conspecific song (zebra finch, in this case) playback elicits a significantly higher response than playback of either heterospecific song types or noise. (BENG: benagalese finch, CAN: canary) Figure from Chew et al, 1996a. Proceedings of the National Academy of Sciences, 93(5), 1950–55. Copyright 1996, National Academy of Sciences, USA. (b) Expression of the IEG ZENK shows a response pattern similar to electrophysiological measures. Baseline levels of Zenk are low in unstimulated zebra finches but increases following auditory stimulation. Expression is greatest following playback of conspecific song, intermediate after heterospecific song, and near baseline after tone stimuli. Figure adapted from Mello et al., 1992. Song presentation induces gene expression in the songbird forebrain. Proceedings of the National Academy of Sciences, 89 (15), 6818–22. Copyright 1992, National Academy of Sciences, USA.

Figure 3

ZENK-ir cells in NCM of blank-implanted and Estrogen implanted female white-throated sparrows listening to song (grey bars) or synthetic tones (white bars). Birds hearing song had more ZENK-ir cells than those hearing tones, but this effect was significant only in E2-treated birds. Among the birds hearing tones, E2-birds had significantly fewer ZENK-ir cells in NCM than blank-implanted birds. Used with permission from Maney, DL; Cho, E & Goode, CT (2006). Estrogen-dependent selectivity of genomic responses to birdsong. European Journal of Neuroscience, 23(6), 1523-9. Copyright 2006, Wiley.

Figure 4

Figure 4a and 4b. Manipulation of estradiol levels within NCM alters neural responses to auditory stimuli playback following injection of estradiol (a) or the aromatase inhibitor ATD (b). X-axes represent the ratio of multiunit response amplitudes of NCM to playback of sound stimuli (pre/post). Pictured are two examples from Tremere et al, 2009, representing changes in response amplitude that occur in response to conspecific song and reversed song stimuli (CON: conspecific song, REV: a conspecific song played in reverse). Figure used with permission from Journal of Neuroscience, 29 (18), Copyright 2009, Society for Neuroscience.

Figure 5

NCM activity to conspecific song playback increased during microinfusion of estrogen (left panel), relative to microinfusion of aCSF in the same animals. Though a decrease in response was not observed when estrogen synthesis was blocked by administering the aromatase inhibitor Fadrozole (right panel), responses “rebounded” during the drug washout period. Figure from Remage-Healey et al., 2010. Brain estrogens rapidly strengthen auditory encoding and guide song preference in a songbird. Proceedings of the National Academy of Sciences, 107(8), 3852-7. Copyright 2010, National Academy of Sciences, USA.

Figure 6

A hypothetical flow chart depicting how estradiol might act in the brain to modulate behavior during the process of song matching in a territorial songbird. Top: A resident male hears an unfamiliar conspecific male singing nearby. A baseline level of estradiol (reflecting seasonal factors) allows the bird to make coarse discriminations among categories of sounds, thus identifying the song as that of an intruder. As the intruder continues to sing, estradiol concentrations within NCM increase as a result of rapid pre-synaptic “synaptocrine” signaling mechanisms that rapidly convert androgen precursors. Estradiol interacts with NCM neurons though non-genomic mechanisms and both increases responses to song and sharpens discrimination. As a result, the resident male and counter-sings an appropriate matching song and successfully defends his territory. During this interaction, conspecific song induces immediate early genes (e.g. ZENK) in NCM neurons, initiating a signaling cascade that enables the male to form memories of the intruder’s songs. Bottom: Following this territorial dispute, the resident male hears the song of his new neighbor once again. Estradiol may contribute to recognition of his neighbor’s song. Electrophysiological responses are lower and adapt more slowly to repeated hearings of the song (reflecting a memory for the song), compared with the previous encounter. As a result, the bird recognizes the song and does not engage in aggressive behavior towards his neighbor. In addition, ZENK is induced at a low level, typical of familiar songs. (E2: estradiol, ER: estrogen receptor, NT: neurotransmitter)