Kathy W. Nordeen - US grants

The aim of this proposal is to uncover functional relationships between neuroanatomical change and vocal learning in passerine songbirds. In zebra finches, song behavior is androgen-dependent, and normally produced only by males. Vocal development involves a sensory phase during which birds memorize a song model, and a sensorimotor phase when birds use auditory feedback to match their own vocalizations to this memory. Each phase occurs during a restricted developmental period which, in male zebra finches, overlaps with dramatic changes in neuron number and connectivity among the neural regions controlling song. The studies proposed have two specific goals; 1) to determine how ontogenetic changes in the anatomy of song-related brain regions influence, or are influenced by vocal development, and 2) to assess or better define the role of specific neural regions in vocal learning. Much of the proposed research will employ females that have been masculinized by steroids shortly after hatching. These females exhibit ontogenetic changes in song regions that mimic those in males, and develop song when stimulated with androgens. Importantly, sensorimotor learning in masculinized females can be offset from these neural changes by manipulating the timing of androgen exposure. Hormonal manipulations and behavioral analyses will be used to determine if the critical period for sensory learning is terminated by androgenic stimulation of vocal practice, or by ontogenetic changes in song-related neural regions. Behavioral analyses will also be used to determine if overlap between ontogenetic changes in neural structure and sensorimotor learning facilitates song learning. Light microscopic analyses and anterograde amino acid autoradiography will be used to determine whether androgens and/or sensorimotor learning augment changes in neuron number or projections of song-control nuclei. In order to identify neural changes unique to song learning, androgenic effects on neural structure will be assessed in masculinized females deafened to prevent sensorimotor learning. Finally, electrolytic and neurochemical lesions will be performed to further our understanding of the functional role of several song nuclei. Striking similarities between vocal development in songbirds and language acquistion in humans argue that a better understanding of neural mechanisms of song learning may provide insight into neural pathologies underlying learning disorders in general, and more specifically, abnormalities in language acquistion.

DESCRIPTION (Adapted from applicant's abstract): Avian song learning is a powerful model for studying how experience influences neural and behavioral development. During song learning, birds memorize conspecific songs and use auditory feedback to shape their vocalizations to these stored models. This song learning often is restricted to species-specific sensitive periods, and this proposal is aimed at identifying neural events that encourage and constrain this learning. The studies focus upon two neural events that accompany song learning: developmental changes in the density and pharmacology of the N-methyl-D-aspartate (NMDA) glutamate receptor subtype, and a massive addition of new circuitry within the vocal motor pathway. NMDA receptors have been linked to many instances of experience-dependent neural plasticity and their activation is necessary for the memorization phase of song learning. Behavioral pharmacology and Golgi staining will be combined in zebra finches to determine whether NMDA receptor activation prompts the decline in dendritic spines that occurs in one song region during learning. Also, receptor autoradiography will be used to determine 1) if auditory manipulations that delay closure of the sensitive song learning period similarly extend developmental changes in NMDA receptor density or pharmacology, 2) if hormonal manipulations that affect song development alter the developmental profile of NMDA receptor expression, and 3) if recurring periods of vocal plasticity in adult canaries are accompanied by changes in NMDA receptor density or pharmacology. The second set of experiments will explore further the hypothesis that neuronal incorporation within the vocal motor pathway regulates behavioral plasticity. Retrograde tracing will be used in zebra finches to identify cell types contributing to a provocative correlation between the number of song-related neurons and the amount of song material learned. Also, measurements and manipulations of yolk testosterone levels will be used to assess if variations in prehatch hormone levels relate to individual differences in neuron number or learning capacity. Finally, adult Bengalese and zebra finches will be compared using thymidine autoradiography and retrograde tracing to determine if species differences in HVC neuron addition may account for species differences in vocal deterioration after deafening. Many behaviors (e.g., language acquisition, social attachment, imprinting) exhibit developmental changes in their sensitivity to environmental stimuli, and these studies will help define neural mechanisms that encourage learning and constrain periods of unique susceptibility.

Instances of early learning (e.g. language acquisition, imprinting, birdsong learning) illustrate that the nervous system's ability to change in response to experience is exaggerated during distinct sensitive periods in development. This proposal is aimed at identifying biological conditions that foster this developmental plasticity by investigating the molecular mechanisms by which gonadal androgens influence the timing of vocal learning in birds. Drawing on earlier work demonstrating that activation of forebrain N-Methyl-D aspartate receptors is critical for vocal learning, and the closure of the sensitive learning period is associated with a decrease in this receptor subtype, the proposed studies will employ quantitative measures of gene expression to determine if androgens regulate developmental changes in NMD receptor expression and composition to control when learning occurs. The work will broaden our understanding of how hormones affect neural and behavioral plasticity, and also may reveal strategies for augmenting learning and memory in later life.

This project focuses on the neural processes by which learned motor skills are adjusted when feedback from an animal's actions deviates from expectations. Studies utilize a well-described neural circuit controlling learned birdsong, and will investigate brain mechanisms that promote behavioral change when auditory feedback from an animal's vocalizations deviates from previously learned patterns. The focus is on a forebrain circuit implicated in motor learning across a wide range of vertebrates. Lesions and/or reversible neuronal inactivation will be used to determine if this forebrain circuit is directly responsible for vocal experimentation when auditory feedback signals the need for vocal change. Also, neuroanatomical measures will establish if such feedback-driven behavioral plasticity entails changes in neuronal connections within motor pathways, and whether the propensity for such neural change decreases in older animals. The project will provide training in behavioral, neuropharmacological, and neuroanatomical methods for both undergraduate and graduate students. Additionally, knowledge derived from these studies will find its way quickly into the classroom, as the investigators are involved heavily in both undergraduate and graduate neuroscience programs. The broad aims are to understand better how the brain evaluates the consequences of behavior, and to identify some of the mechanisms it uses to adaptively adjust behavior. This information will provide insights into general mechanisms of motor learning and development, as well as adult neural and behavioral plasticity. The work should impact a variety of disciplines ranging from cognitive and sensory-motor neuroscience to neural reorganization.