Neuroestrogens rapidly shape auditory circuits to support communication learning and perception: Evidence from songbirds

Vahaba, Daniel M.; Remage‐Healey, Luke

doi:10.1016/j.yhbeh.2018.03.007

Cited by 33 publications

(12 citation statements)

References 225 publications

(243 reference statements)

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“…Thus, this review will focus on sex differences in aromatase expression and activity in the brain of mammalian species only. However, it is important to note that non-mammalian species are also known to express aromatase in the brain, and research in non-mammalian species (e.g., birds and fish) has also proven useful; the reader is referred to these cited references for further analyses on those species ( Balthazart, 1997 ; Cao et al, 2012 ; Vahaba and Remage-Healey, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Sexually Dimorphic Effects of Aromatase on Neurobehavioral Responses

Shay

Vieira‐Potter

Rosenfeld

2018

Front. Mol. Neurosci.

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Aromatase is the enzyme responsible for converting testosterone to estradiol. In mammals, aromatase is expressed in the testes, ovaries, brain, and other tissues. While estrogen is traditionally associated with reproduction and sexual behavior in females, our current understanding broadens this perspective to include such biological functions as metabolism and cognition. It is now well-recognized that aromatase plays a vital lifetime role in brain development and neurobehavioral function in both sexes. Thus, ongoing investigations seek to highlight potentially vital sex differences in the role of aromatase, particularly regarding its centrally mediated effects. To characterize the role of aromatase in mediating such functions, effects of aromatase inhibitor (AI) treatments on humans and animal models have been determined. Aromatase knockout (ArKO) mice that systemically lack the enzyme have also been employed. Humans possessing mutations in the gene encoding aromatase, CYP19, have also provided critical insight into how aromatase affects brain function in a possible sex-dependent manner. A better understanding of how AIs, used to treat breast cancer and other clinical conditions, may detrimentally affect neurobehavioral responses will likely promote development of future therapies to combat these effects. Herein, we will provide a critical review of the current knowledge of sex differences in aromatase regulation of various neurobehavioral functions. Although many species have been used to better understand the functions of aromatase, this review focuses on rodent models and humans. Critical gaps in our present understanding of this area will be considered, and important future research directions will be discussed.

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Section: Introductionmentioning

confidence: 99%

Sexually Dimorphic Effects of Aromatase on Neurobehavioral Responses

Shay

Vieira‐Potter

Rosenfeld

2018

Front. Mol. Neurosci.

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“…Parvalbumin is a marker for a unique subpopulation of inhibitory interneurons 54 , is co-localized with aromatase in NCM 55 , and its presence often denotes changes in critical period plasticity within mammalian visual cortex 56 , as well as songbird song circuits 57 . Further, E2 may modulate auditory circuits by modulating inhibitory interneurons such as PV+ cells 37 . We focused solely on males as they were the sex of interest for subsequent song and physiology experiments in this study.…”

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confidence: 99%

Neuroestrogen synthesis modifies neural representations of learned song without altering vocal imitation in developing songbirds

Vahaba

Hecsh

Remage‐Healey

2020

Sci Rep

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Birdsong learning, like human speech, depends on the early memorization of auditory models, yet how initial auditory experiences are formed and consolidated is unclear. In songbirds, a putative cortical locus is the caudomedial nidopallium (NCM), and one mechanism to facilitate auditory consolidation is 17β-estradiol (E2), which is associated with human speech-language development, and is abundant in both NCM and human temporal cortex. Circulating and NCM E2 levels are dynamic during learning, suggesting E2's involvement in encoding recent auditory experiences. Therefore, we tested this hypothesis in juvenile male songbirds using a comprehensive assessment of neuroanatomy, behavior, and neurophysiology. First, we found that brain aromatase expression, and thus the capacity to synthesize neuroestrogens, remains high in the auditory cortex throughout development. Further, while systemic estrogen synthesis blockade suppressed juvenile song production, neither systemic nor unilateral E2 synthesis inhibition in NCM disrupted eventual song imitation. Surprisingly, early life neuroestrogen synthesis blockade in NCM enhanced the neural representations of both the birds' own song and the tutor song in NCM and a downstream sensorimotor region, HVC, respectively. Taken together, these findings indicate that E2 plays a multifaceted role during development, and that, contrary to prediction, tutor song memorization is unimpaired by unilateral estrogen synthesis blockade in the auditory cortex. While many animals use sounds to communicate with one another (vocal communication), the ability to learn to vocally communicate is relatively rare 1. In vocal learning animals, such as humans and songbirds, vocal learning occurs across two main phases: an auditory memorization ('sensory') phase, followed by a sensorimotor phase ('babbling' , error correction/feedback) 2,3. While much is known about sensorimotor learning, the mechanisms that guide the formation and consolidation of auditory memories early in life are less clear. One brain region likely involved in storing auditory memories in songbirds is the caudomedial nidopallium (NCM) 4. NCM, comparable to mammalian secondary auditory cortex, is required for accurate song learning. Blocking ERK-signaling or mTOR bilaterally in NCM during tutoring leads to poor song imitation 5,6. Tutoring naïve juvenile songbirds leads to an increased proportion of tutor-song-selective neurons in NCM 7. Further, bilateral NCM lesions abolish innate preference for tutor song in adults 8 , but see 9,10. Thus, NCM contains a putative tutor 'engram'; however, the neuromodulatory mechanisms that shape this auditory memory formation and consolidation remain unknown. Consolidating recent experience in other contexts and systems require presynaptic signaling molecules ('neuromodulators'), such as brain-derived estrogens 11. The predominant estrogen 17β-estradiol (E2) is a candidate neuromodulator required for auditory memory consolidation, as is evident in a similar role in adult hippocampal-dependent cognit...

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“…Extensive evidence exists for sex hormones' influence on both brain plasticity, as well as language development, cognition, learning, and memory (Anthoni et al, 2012;Bailey et al, 2017;Frick et al, 2015;Friederici et al, 2008;Hahn et al, 2016;Hamson et al, 2016;Hawley et al, 2013;Leonard and Winsauer, 2011;Postma et al, 2000;Schaadt et al, 2015;Vahaba and Remage-Healey, 2018). Nonetheless, there are still gaps in our understanding of the complex interplay between sex hormones, brain, and behavior.…”

Section: Discussionmentioning

confidence: 99%

Singing-related reorganization of the song motor circuit is accompanied by a shift in hormonal modulation of song

Rocha

Dreier

Brewer

et al. 2020

Preprint

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Sex hormones are essential modulators of birdsong. Testosterone, and its active androgenic and estrogenic metabolites, 5α-dihydrotestosterone (DHT) and estradiol, can re-shape the brain circuits responsible for song learning and production. The differential mechanisms of action of these different hormones during song development and song maintenance are, nonetheless, not fully understood. Here we demonstrate that unlike testosterone, DHT treatment does not induce singing behavior in naïve adult female canaries that have never previously produced song. However, in birds with previous testosterone-induced singing experience, DHT alone is enough to promote the re-acquisition of high quality songs, even after months of silence. In addition, we show that the synaptic reorganization that accompanies vocal motor skill development requires more than DHT-induced androgen receptor activation. These results indicate that vocal motor practice will persistently modify the hormone-sensitive brain circuit responsible for song production, suggesting a mechanistic differentiation in the hormone-dependent regulation of the initial vocal motor skill acquisition and later re-acquisition.

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Neuroestrogens rapidly shape auditory circuits to support communication learning and perception: Evidence from songbirds

Cited by 33 publications

References 225 publications

Sexually Dimorphic Effects of Aromatase on Neurobehavioral Responses

Sexually Dimorphic Effects of Aromatase on Neurobehavioral Responses

Neuroestrogen synthesis modifies neural representations of learned song without altering vocal imitation in developing songbirds

Singing-related reorganization of the song motor circuit is accompanied by a shift in hormonal modulation of song

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