2001 — 2004 |
London, Sarah E |
F31Activity Code Description: To provide predoctoral individuals with supervised research training in specified health and health-related areas leading toward the research degree (e.g., Ph.D.). |
Developmental Differences in Brain Androgen Synthesis @ University of California Los Angeles
DESCRIPTION (provided by applicant): The zebra finch song system consists of sexually dimorphic nuclei. Early estrogen treatment masculinizes telencephalic song nuclei in genetic females, but blocking estrogen does not demasculinize these nuclei in genetic males. Studies have suggested that the existence of a genetic factor intrinsic to the brain underlies the masculine pattern of song system organization. Recently, a sex difference has been seen in transcriptional levels of 17 alpha hydroxylase (CYP 17), the enzyme that makes androgen, in the telencephalon of developing zebra finches. It is hypothesized that GYP 17 expression extends through the steroid sensitive period of song system development, and is distributed near the song nuclei. This will be investigated using in situ hybridization. It is hypothesized that the different levels of CYP17 mRNA reflect sex differences in protein-mediated transcriptional regulation. DNA sequence from the promoter region of the CYP 17 gene will be determined by screening a cDNA library, performing 5? RACE, and screening a zebra finch genomic library. This represents a first step in identifying the factors that differentially regulate CYP 17 transcription in the telencephalon of developing male and female zebra finch. They will also indicate potential regulatory mechanisms for androgen synthesis in other species, including humans.
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0.942 |
2008 — 2009 |
London, Sarah E |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
The Molecular Basis For Developmental Sensory Learning @ University of Illinois Urbana-Champaign
[unreadable] DESCRIPTION (provided by applicant): [unreadable] [unreadable] Similar to humans, songbirds learn meaningful vocalizations from an adult tutor most effectively during a sensitive period of development. While advancements have been made in understanding the motor control of vocal production, the neural mechanisms for the sensory memories that precede and direct vocal structure are mostly undefined. In songbirds like the zebra finch, the forebrain auditory lobule (AL), the functional homologue of mammalian primary and secondary auditory cortices, is involved in adult song recognition and holds a trace of the tutor song heard during juvenile life. Thus, it may be that AL is required for developmental sensory tutor song learning. Further, gene expression studies demonstrate that genes only induced in learning-related contexts in adult songbirds are constitutively expressed in AL during the sensory phase of developmental song learning. Therefore, the hypothesis was that AL, and developmentally and experientially regulated gene expression in AL, are necessary for optimal sensory song learning during development. To test this hypothesis, three studies were designed to (1) behaviorally test that AL and molecular processes within AL are required for tutor song memorization, (2) silence individual genes in AL to test their function in developmental sensory song learning, and (3) identify and confirm a suite of genes that may shape the AL for optimal sensory learning. These studies form a comprehensive and cohesive investigation of the molecular events underlying the sensory song learning that is the foundation for song vocalizations. The zebra finch is a very useful model for these studies because some sensory song learning occurs before vocalization begins, allowing the dissection of sensory from motor and sensorimotor components of developmental song learning. The function of AL and many genes are evolutionarily conserved, thus results of these experiments have application not only to songbird researchers but also those interested in human language acquisition. > The ability to communicate is fundamental, and most people use vocal communication to navigate through their complex social lives. Vocal learning is most efficient during early life, progresses similarly to how birds learn song, and both people and birds rely primarily upon sensory processing of the vocalizations they hear to shape their own vocalizations. Thus, the study of sensory learning of tutor song in songbirds provides important insights into auditory mechanisms underlying human language acquisition. [unreadable] [unreadable] [unreadable]
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1 |
2019 |
London, Sarah E |
R56Activity Code Description: To provide limited interim research support based on the merit of a pending R01 application while applicant gathers additional data to revise a new or competing renewal application. This grant will underwrite highly meritorious applications that if given the opportunity to revise their application could meet IC recommended standards and would be missed opportunities if not funded. Interim funded ends when the applicant succeeds in obtaining an R01 or other competing award built on the R56 grant. These awards are not renewable. |
Mechanisms of Age- and Experience-Dependent Neural Plasticity and Behavior
PROJECT SUMMARY. We have made astounding progress in our understanding of how experience triggers change in the adult nervous system for learning and long-term memory formation. Learning in developing systems highlights a feature of learning often overlooked: the ability to learn from the same experience is not always equivalent. This means that properties of the brain can change such that sometimes they can learn and other times they cannot. Because early life experience can have profound and lasting effects on typical and atypical cognitive function and behavior, it is essential to understand what neural characteristics modulate experience-dependent plasticity. Learning requires integrated processes of receptivity and responsivity; a neural circuit must be established yet flexible such that it is possible to initiate experience-dependent change and effectively respond to experience. It is difficult to examine these features in adults, and with existing methodologies that limit integration of these two levels of cellular learning. Here, we propose a strategy that takes advantage of a model that undergoes extreme fluctuations in the ability to learn. A juvenile male zebra finch songbird can only form the memory of another ?tutor? bird?s song, which he uses to structure his own song, during 35 days in development. This occurs despite constant, daily exposure to singing birds. With this system as part of the experimental toolset, we can assay chromatin landscapes and enhancers in a brain area required for tutor song memorization to track baseline changes in cellular status that set receptivity. We can also use biochemical assays to selectively identify proteins actively synthesized after song experience. These two properties combined, in the context of birds we know can or cannot memorize tutor song, will provide unique, integrated maps of cell subtypes and molecular processes that promote and limit the ability to learn.
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0.964 |