Hippocampal Aromatization Modulates Spatial Memory and Characteristics of the Synaptic Membrane in the Male Zebra Finch

Bailey, David J.; Makeyeva, Yekaterina V.; Paitel, Elizabeth R.; Pedersen, Alyssa L.; Hon, Angel T.; Gunderson, Jordan A.; Saldanha, Colin J.

doi:10.1210/en.2016-1692

Cited by 32 publications

(31 citation statements)

References 66 publications

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“…This is in contrast to evidence suggesting E2's importance in consolidating other sensory memories (e.g. chemosensory in rodent olfactory bulb 120 ) and spatial memory consolidation in the hippocampus of songbirds and rodents 26,97 . In rodents, E2 is rapidly upregulated in dorsal hippocampus immediately following an object recognition training session 28 .…”

Section: Discussioncontrasting

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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Section: Discussioncontrasting

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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“…Repeated exposures of a single conspecific song leads to neural 'recognition' up 48 hours later (Chew et al, 1995), which is impaired when global estrogen production is dampened (Yoder et al, 2012). Our findings suggest that while E2 is important for spatial memory consolidation in the hippocampus of both birds and rodents (Frick, 2015;Bailey et al, 2017), as well as chemosensory memories in the olfactory bulb (Dillon et al, 2013), this role does not extend to auditory cortex. In rodents, E2 is rapidly upregulated in dorsal hippocampus immediately following an object recognition training session (Tuscher et al, 2016).…”

Section: Recent Auditory Experience Consolidation Is Insensitive To Ementioning

confidence: 75%

“…Consolidating recent experience in other contexts and systems require presynaptic signaling molecules ('neuromodulators'), such as brain-derived estrogens. 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 cognition, across taxa (Vierk et al, 2012;Srivastava et al, 2013;Luine, 2014) (Woolley and McEwen, 1992;Packard and Teather, 1997;Packard, 1998;Woolley, 2007;Frick, 2012;Bailey et al, 2013;Rensel et al, 2013;Bailey and Saldanha, 2015;Rensel et al, 2015;Barth et al, 2016;Tuscher et al, 2016;Bailey et al, 2017;Blaustein, 2017;Bayer et al, 2018), but see (Korol and Pisani, 2015). Additionally, both circulating and brain-derived estrogens ('neuroestrogens') typically enhance hearing (Caras, 2013;Caras and Remage-Healey, 2016), and are associated with language and verbal memory in humans (Fernandez et al, 2003;Zimmerman et al, 2011;Anthoni et al, 2012;Wermke et al, 2014;Schaadt et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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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“…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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Hippocampal Aromatization Modulates Spatial Memory and Characteristics of the Synaptic Membrane in the Male Zebra Finch

Cited by 32 publications

References 66 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

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

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