Clustered organization and region‐specific identities of estrogen‐producing neurons in the forebrain of Zebra Finches (<i>Taeniopygia guttata</i>)

Ikeda, Maaya Z.; Krentzel, Amanda A.; Oliver, Tessa J.; Scarpa, Garrett B.; Remage‐Healey, Luke

doi:10.1002/cne.24292

Cited by 23 publications

(57 citation statements)

References 80 publications

(129 reference statements)

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“…It is worth noting that our treatments were presented unilaterally, and there is thus a strong likelihood that contralateral NCM can compensate for depressed E2 production in our study, leading to robust tutor song memory and proper song imitation in adulthood. While NCM appears to have lateralized function both natively 112 , and with regard to the acute actions of E2 38,113 , there is scant evidence for lateralized expression of aromatase 50,55 . Relatedly, there is the additional possibility that either acute (microdialysis) or chronic (systemic) administrations may lead to homeostatic increases in aromatase production and/or activity e.g.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to aromatase, we were also curious as to whether transitions between learning phases were associated with differences in expression of the calcium buffering-protein parvalbumin (PV). 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 .…”

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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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Section: Discussionmentioning

confidence: 99%

mentioning

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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“…Antibodies and dilutions for aromatase and parvalbumin were identical to those used in Ikeda et al (2017). Briefly, we used a polyclonal anti-aromatase primary antibody raised in rabbit (1:2,000; a generous gift from Dr. Colin Saldanha), and a monoclonal anti-parvalbumin primary antibody raised in mouse (1:10,000; Millipore MAB1572; RRID: AB_2174013).…”

Section: Antibodiesmentioning

confidence: 99%

“…Parvalbumin is a marker for a unique subpopulation of inhibitory interneurons (Tremblay et al, 2016), is co-localized with aromatase in NCM (Ikeda et al, 2017), and its presence often denotes changes in critical period plasticity within mammalian visual cortex (Hensch, 2005), as well as songbird song circuits (Balmer et al, 2009). We focused solely on males as they were the sex of interest for subsequent song and physiology experiments in this study.…”

Section: Cell Density Is Region-and Age-dependent In Developing Auditmentioning

confidence: 99%

“…It is worth noting that our treatments were presented unilaterally, and there is thus a strong likelihood that contralateral NCM can compensate for depressed E2 production in our study, leading to robust tutor song memory and proper song imitation in adulthood. While NCM appears to have lateralized function both natively (Moorman and Nicol, 2014), and with regards to E2 (Remage-Healey et al, 2010;De Groof et al, 2017), there is scant evidence for lateralized expression of aromatase (Saldanha et al, 2000;Ikeda et al, 2017). Relatedly, there is the additional possibility that either acute (microdialysis) or chronic (systemic) administrations may lead to homeostatic increases in aromatase production and/or activity (e.g.…”

Section: Developmental Neuroestrogen Synthesis Blockade Has Enduring mentioning

confidence: 99%

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Blocking neuroestrogen synthesis modifies neural representations of learned song without altering vocal imitation accuracy in developing songbirds

Hecsh

Remage‐Healey

2019

Preprint

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Birdsong, like human speech, is learned early in life by first memorizing an auditory model. Once memorized, birds compare their own burgeoning vocalizations to their auditory memory, and adjust their song to match the model. While much is known about this latter part of vocal learning, less is known about how initial auditory experiences are formed and consolidated. In both adults and developing songbirds, there is strong evidence suggesting the caudomedial nidopallium (NCM), a higher order auditory forebrain area, is the site of auditory memory consolidation. However, the mechanisms that facilitate this consolidation are poorly understood. One likely mechanism is 17β-estradiol (E2), which is associated with speech-language development and disorders in humans, and is abundant in both mammalian temporal cortex and songbird NCM. Circulating E2 is also elevated during the auditory memory phase, and in NCM immediately after song learning sessions, suggesting it functions to encode recent auditory experience. Therefore, we tested a role for E2 production in auditory memory consolidation during development using a comprehensive set of investigations to ask this question at the level of neuroanatomy, neurophysiology, and behavior. Our results demonstrate that while systemic estrogen synthesis blockade regulates juvenile song production, inhibiting E2 synthesis locally within NCM does not adversely affect song learning outcomes. Surprisingly, early life E2 manipulations in NCM modify the neural representations of birds' own song and the model tutor song in both NCM and a downstream sensorimotor nucleus (HVC). Further, we show that the capacity to synthesize neuroestrogens remains high throughout development alongside substantial changes in NCM cell density across age. Taken together, these findings suggest that E2 plays a multifaceted role during development, and demonstrate that contrary to prediction, unilateral post-training estrogen synthesis blockade in the auditory cortex does not negatively impact vocal learning. Acute downregulation of neuroestrogens are therefore likely permissive for juvenile auditory memorization, while neuroestrogen synthesis influences communication production and representation in adulthood. AntibodiesAntibodies and dilutions for aromatase and parvalbumin were identical to those used in Ikeda et al. (2017). Briefly, we used a polyclonal anti-aromatase primary antibody raised in rabbit (1:2,000; a generous gift from Dr. Colin Saldanha), and a monoclonal anti-parvalbumin primary antibody raised in mouse (1:10,000; Millipore MAB1572; RRID: AB_2174013). Secondary antibodies included goat antirabbit Alexa 488 (1:500; Thermo Fisher Scientific Inc.), and goat anti-mouse Alexa 647 (1:100; Thermo Fisher Scientific Inc.). ProcedureBrain sections were first manually washed 3 x in 0.1 M PB, followed by 3 x 15-minute washes in 0.1 M PB on a plate shaker, followed by a 2-hour incubation at room temperature with 10% normal goat serum (Vector) in 0.3 % PBT. Tissue was then transferred to a 10% normal goat...

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Estrogen receptor alpha, G‐protein coupled estrogen receptor 1, and aromatase: Developmental, sex, and region‐specific differences across the rat caudate–putamen, nucleus accumbens core and shell

Krentzel

Willett

Johnson

et al. 2020

J of Comparative Neurology

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Sex steroid hormones such as 17β-estradiol (estradiol) regulate neuronal function by binding to estrogen receptors (ERs), including ERα and GPER1, and through differential production via the enzyme aromatase. ERs and aromatase are expressed across the nervous system, including in the striatal brain regions. These regions, comprising the nucleus accumbens core, shell, and caudate-putamen, are instrumental for a wide-range of functions and disorders that show sex differences in phenotype and/or incidence. Sex-specific estrogen action is an integral component for generating these sex differences. A distinctive feature of the striatal regions is that in adulthood neurons exclusively express membrane but not nuclear ERs. This long-standing finding dominates models of estrogen action in striatal regions. However, the developmental etiology of ER and aromatase cellular expression in female and male striatum is unknown. This omission in knowledge is important to address, as developmental stage influences cellular estrogenic mechanisms. Thus, ERα, GPER1, and aromatase cellular immunoreactivity was assessed in perinatal, prepubertal, and adult female and male rats. We tested the hypothesis that ERα, GPER1, and aromatase exhibits sex, region, and age-specific differences, including nuclear expression. ERα exhibits nuclear expression in all three striatal regions before adulthood and disappears in a region-and sex-specific time-course. Cellular GPER1 expression decreases during development in a region-but not sex-specific time-course, resulting in extranuclear expression by adulthood. Somatic aromatase expression presents at prepuberty and increases by adulthood in a region-but not sex-specific time-course. These data indicate that developmental period exerts critical sex-specific influences on striatal cellular estrogenic mechanisms.

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Clustered organization and region‐specific identities of estrogen‐producing neurons in the forebrain of Zebra Finches (Taeniopygia guttata)

Cited by 23 publications

References 80 publications

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

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

Blocking neuroestrogen synthesis modifies neural representations of learned song without altering vocal imitation accuracy in developing songbirds

Estrogen receptor alpha, G‐protein coupled estrogen receptor 1, and aromatase: Developmental, sex, and region‐specific differences across the rat caudate–putamen, nucleus accumbens core and shell

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