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Nicole J Gervais, Luke Remage-Healey, Joseph R Starrett, Daniel J Pollak, Jessica A Mong, Agnès Lacreuse
Breast cancer patients using aromatase inhibitors (AIs) as an adjuvant therapy often report side effects including hot flashes, mood changes, and cognitive impairment. Despite long-term use in humans, little is known about the effects of continuous AI administration on the brain and cognition. We used a primate model of human cognitive aging, the common marmoset, to examine the effects of a 4-week daily administration of the AI Letrozole (20 μg, p.o.) on cognition, anxiety, thermoregulation, brain estrogen content, and hippocampal pyramidal cell physiology...
December 26, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Luke Remage-Healey, Elena Choleris, Jacques Balthazart
No abstract text is available yet for this article.
June 22, 2018: Hormones and Behavior
Daniel M Vahaba, Luke Remage-Healey
Steroid hormones, such as estrogens, were once thought to be exclusively synthesized in the ovaries and enact transcriptional changes over the course of hours to days. However, estrogens are also locally synthesized within neural circuits, wherein they rapidly (within minutes) modulate a range of behaviors, including spatial cognition and communication. Here, we review the role of brain-derived estrogens (neuroestrogens) as modulators within sensory circuits in songbirds. We first present songbirds as an attractive model to explore how neuroestrogens in auditory cortex modulate vocal communication processing and learning...
March 29, 2018: Hormones and Behavior
Valerie L Hedges, Gang Chen, Lei Yu, Amanda A Krentzel, Joseph R Starrett, Jing-Ning Zhu, Piratheepan Suntharalingam, Luke Remage-Healey, Jian-Jun Wang, Timothy J Ebner, Paul G Mermelstein
Estrogens affect cerebellar activity and cerebellum-based behaviors. Within the adult rodent cerebellum, the best-characterized action of estradiol is to enhance glutamatergic signaling. However, the mechanisms by which estradiol promotes glutamatergic neurotransmission remain unknown. Within the mouse cerebellum, we found that estrogen receptor activation of metabotropic glutamate receptor type 1a strongly enhances neurotransmission at the parallel fiber-Purkinje cell synapse. The blockade of local estrogen synthesis within the cerebellum results in a diminution of glutamatergic neurotransmission...
March 1, 2018: Endocrinology
Amanda A Krentzel, Matheus Macedo-Lima, Maaya Z Ikeda, Luke Remage-Healey
Estradiol acts as a neuromodulator in brain regions important for cognition and sensory processing. Estradiol also shapes brain sex differences but rarely have these concepts been considered simultaneously. In male and female songbirds, estradiol rapidly increases within the auditory forebrain during song exposure and enhances local auditory processing. We tested whether G-protein-coupled estrogen receptor 1 (GPER1), a membrane-bound estrogen receptor, is necessary and sufficient for neuroestrogen regulation of forebrain auditory processing in male and female zebra finches (Taeniopygia guttata)...
March 1, 2018: Endocrinology
Jacques Balthazart, Elena Choleris, Luke Remage-Healey
This brief commentary reviews key steps in the history of steroid endocrinology that have resulted in important conceptual shifts. Our understanding of the "Fast Effects of Steroids" now reflect substantial progress, including the major concept that steroids act rapidly on a variety of physiological and behavioral responses, via mechanisms that are too fast to be fully accounted for by classical receptor-dependent regulation of gene transcription. Several so-called 'non-classical' mechanisms have been identified and include binding to membrane receptors and regulating non genomic signaling cascades...
March 2018: Hormones and Behavior
Dana L Moseley, Narendra R Joshi, Jonathan F Prather, Jeffrey Podos, Luke Remage-Healey
In humans and other animals, behavioural variation in learning has been associated with variation in neural features like morphology and myelination. By contrast, it is essentially unknown whether cognitive performance scales with electrophysiological properties of individual neurons. Birdsong learning offers a rich system to investigate this topic as song acquisition is similar to human language learning. Here, we address the interface between behavioural learning and neurophysiology in a cohort of wild-caught, hand-reared songbirds (swamp sparrows, Melospiza georgiana)...
December 11, 2017: Scientific Reports
Vanessa Lee, Benjamin A Pawlisch, Matheus Macedo-Lima, Luke Remage-Healey
Norepinephrine (NE) can dynamically modulate excitability and functional connectivity of neural circuits in response to changes in external and internal states. Regulation by NE has been demonstrated extensively in mammalian sensory cortices, but whether NE-dependent modulation in sensory cortex alters response properties in downstream sensorimotor regions is less clear. Here we examine this question in male zebra finches, a songbird species with complex vocalizations and a well-defined neural network for auditory processing of those vocalizations...
January 1, 2018: Journal of Neurophysiology
Maaya Z Ikeda, Amanda A Krentzel, Tessa J Oliver, Garrett B Scarpa, Luke Remage-Healey
A fast, neuromodulatory role for estrogen signaling has been reported in many regions of the vertebrate brain. Regional differences in the cellular distribution of aromatase (estrogen synthase) in several species suggest that mechanisms for neuroestrogen signaling differ between and even within brain regions. A more comprehensive understanding of neuroestrogen signaling depends on characterizing the cellular identities of neurons that express aromatase. Calcium-binding proteins such as parvalbumin and calbindin are molecular markers for interneuron subtypes, and are co-expressed with aromatase in human temporal cortex...
December 1, 2017: Journal of Comparative Neurology
Lauren M Rudolph, Charlotte A Cornil, Melinda A Mittelman-Smith, Jennifer R Rainville, Luke Remage-Healey, Kevin Sinchak, Paul E Micevych
Over the past two decades, the classical understanding of steroid action has been updated to include rapid, membrane-initiated, neurotransmitter-like functions. While steroids were known to function on very short time spans to induce physiological and behavioral changes, the mechanisms by which these changes occur are now becoming more clear. In avian systems, rapid estradiol effects can be mediated via local alterations in aromatase activity, which precisely regulates the temporal and spatial availability of estrogens...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Daniel M Vahaba, Luke Remage-Healey
The vertebrate central nervous system integrates cognition and behavior, and it also acts as both a source and target for steroid hormones like estrogens. Recent exploration of brain estrogen production in the context of learning and memory has revealed several common themes. First, across vertebrates, the enzyme that synthesizes estrogens is expressed in brain regions that are characterized by elevated neural plasticity and is also integral to the acquisition, consolidation, and retrieval of recent experiences...
December 2015: Current Opinion in Behavioral Sciences
Jennifer J Tuscher, Julia S Szinte, Joseph R Starrett, Amanda A Krentzel, Ashley M Fortress, Luke Remage-Healey, Karyn M Frick
The potent estrogen 17β-Estradiol (E2) plays a critical role in mediating hippocampal function, yet the precise mechanisms through which E2 enhances hippocampal memory remain unclear. In young adult female rodents, the beneficial effects of E2 on memory are generally attributed to ovarian-synthesized E2. However, E2 is also synthesized in the adult brain in numerous species, where it regulates synaptic plasticity and is synthesized in response to experiences such as exposure to females or conspecific song...
July 2016: Hormones and Behavior
Eliot A Brenowitz, Luke Remage-Healey
Birds commonly use sound for communication between the sexes. In many songbird species, only males sing and there are pronounced sex differences in the neural song control circuits. By contrast, the auditory circuitry is largely similar in males and females. Both sexes learn to recognize vocalizations heard as juveniles and this shapes auditory response selectivity. Mating vocalizations are restricted to the breeding season, when sex steroid levels are elevated. Auditory cells, from the ear to the cortex, are hormone sensitive...
June 2016: Current Opinion in Neurobiology
Maaya Z Ikeda, Sung David Jeon, Rosemary A Cowell, Luke Remage-Healey
The catecholamine norepinephrine plays a significant role in auditory processing. Most studies to date have examined the effects of norepinephrine on the neuronal response to relatively simple stimuli, such as tones and calls. It is less clear how norepinephrine shapes the detection of complex syntactical sounds, as well as the coding properties of sensory neurons. Songbirds provide an opportunity to understand how auditory neurons encode complex, learned vocalizations, and the potential role of norepinephrine in modulating the neuronal computations for acoustic communication...
June 24, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Amanda A Krentzel, Luke Remage-Healey
The actions of estrogens have been associated with brain differentiation and sexual dimorphism in a wide range of vertebrates. Here we consider the actions of brain-derived 'neuroestrogens' in the forebrain and the accompanying differences and similarities observed between males and females in a variety of species. We summarize recent evidence showing that baseline and fluctuating levels of neuroestrogens within the auditory forebrain of male and female zebra finches are largely similar, and that neuroestrogens enhance auditory representations in both sexes...
July 2015: Frontiers in Neuroendocrinology
B A Pawlisch, L Remage-Healey
Neuromodulators rapidly alter activity of neural circuits and can therefore shape higher order functions, such as sensorimotor integration. Increasing evidence suggests that brain-derived estrogens, such as 17-β-estradiol, can act rapidly to modulate sensory processing. However, less is known about how rapid estrogen signaling can impact downstream circuits. Past studies have demonstrated that estradiol levels increase within the songbird auditory cortex (the caudomedial nidopallium, NCM) during social interactions...
January 22, 2015: Neuroscience
Maaya Ikeda, Michelle A Rensel, Barney A Schlinger, Luke Remage-Healey
This protocol describes a method for the in vivo measurement of steroid hormones in brain circuits of the zebra finch. A guide cannula is surgically implanted into the skull, microdilysate is collected through a microdialysis probe that is inserted into the cannula, and steroid concentrations in the microdialysate are determined using the enzyme-linked immunosorbent assay (ELISA). In some cases, the steroids measured are derived locally (e.g., neural estrogens in males), whereas in other cases, the steroids measured reflect systemic circulating levels and/or central conversion (e...
December 2014: Cold Spring Harbor Protocols
Andrew Chao, Ashley Paon, Luke Remage-Healey
Estrogens shape brain circuits during development, and the capacity to synthesize estrogens locally has consequences for both sexual differentiation and the acute modulation of circuits during early learning. A recently optimized method to detect and quantify fluctuations in brain estrogens in vivo provides a direct means to explore how brain estrogen production contributes to both differentiation and neuromodulation during development. Here, we use this method to test the hypothesis that neuroestrogens are sexually differentiated as well as dynamically responsive to song tutoring (via passive video/audio playback) during the period of song learning in juvenile zebra finches...
March 2015: Developmental Neurobiology
Luke Remage-Healey
Neurons communicate primarily via action potentials that transmit information on the timescale of milliseconds. Neurons also integrate information via alterations in gene transcription and protein translation that are sustained for hours to days after initiation. Positioned between these two signaling timescales are the minute-by-minute actions of neuromodulators. Over the course of minutes, the classical neuromodulators (such as serotonin, dopamine, octopamine, and norepinephrine) can alter and/or stabilize neural circuit patterning as well as behavioral states...
August 2014: Hormones and Behavior
Barney A Schlinger, Luke Remage-Healey, Michelle Rensel
The specificity of estrogen signaling in brain is defined at one level by the types and distributions of receptor molecules that are activated by estrogens. At another level, as our understanding of the neurobiology of the estrogen synthetic enzyme aromatase has grown, questions have emerged as to how neuroactive estrogens reach specific target receptors in functionally relevant concentrations. Here we explore the spatial specificity of neuroestrogen signaling with a focus on studies of songbirds to provide perspective on some as-yet unresolved questions...
September 1, 2014: General and Comparative Endocrinology
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