Robert J. Dooling - US grants

The present relationship between hearing, vocal learning, and vocal development in a small Australian parrot - the parakeet or budgerigar (Melopsittacus undulatus). While similar in some respects to the more familiar songbirds, vocal learning in budgerigars may also be quite different in significant ways. This is part of the focus of the present proposal. We know already that adult budgerigars have the ability to learn new calls very quickly with a capacity that appears unlimited. Auditory perceptual learning plays a central role in determining the characteristics of the species vocal repertoire. Furthermore, social and visual cues are of paramount importance. From recent cross-modal perceptual experiments, it appears that budgerigars may provide a unique system for examining how acoustic and visual information is coordinated in vocal learning. The proposed experiments will characterize: (1) the nature of perceptual categories for species-specific vocal signals in this species, (2) how the specialized auditory perceptual system of budgerigars is matched to the extraordinary capacity for vocal learning, and (3) what social and visual cues are coordinated to guide the development this learned vocal repertoire. These experiments are aimed at ultimately discovering the general biological principles which are capable of organizing and maintaining a complex, learned vocal communication system. Some of these general biological principles are clearly involved in the development and maintenance of complex, learned behavior in humans - the most relevant instance in the present case being language acquisition. The comparative behavioral approach espoused in this proposal - proceeding as it does with parallel neuroanatomical investigations - offers an exciting opportunity to understand the biological foundations of vertebrate learning.

Birds present an interesting dilemma for classical theories of sound localization. Because of their restricted range of hearing and closely-spaced ears, it is difficult to understand how birds can localize sound at all. Yet, there is clear evidence from playback studies in the field that birds can and do localize a variety of conspecific vocal signals as well as the vocal signals of other species. The present research plan is an ongoing effort to use behavioral techniques to measure Minimum Audible Angles (MAAs) for simple and complex (vocalizations) acoustic signals in an effort to define the acoustic cues by small birds in localizing sound. Preliminary evidence indicates that the budgerigar is remarkably sensitive to changes in spatial location of a pure-tone sound source--suggesting the interaural pathway may be involved. The canary is less sensitive than the budgerigar but shows a particular sensitivity to species-specific contact cells. Comparisons of several species selected for the range of interaural distances and the characteristics and function of their vocal signals should reveal the strategies used by small birds in localizing sound and may provide evidence that locatability is a factor in the design of some avian vocalizations. Calibration experiments will provide confirming evidence for the existence of binaural cues available for sound localization. The present experiments will provide proof of whether there is a new mechanism for localizing sound in small birds. Except for pilot data from this proposal (on budgerigars), there is no evidence that any organism uses an interaural pathway in sound localization. If the present proposal fails to show that budgerigars use the interaural pathway in sound localization, then the nervous system of this species must be extraordinarily adapted for coding binaural intensity in time differences.

We know that at least some species of birds retain the capacity to replace hair cells which are lost following trauma or during aging. In quail, the ganglion cells of the VIIIth nerve, however, are reduced in number following hair cell loss, even though those hair cells are replaced. These results suggest that some active process must be involved if these new hair cells are to be innervated and influence auditory function. Currently little is known about the consequences of hair cell regeneration on hering. This proposal compares the functional consequences (i.e. the effects on hearing) of hair cell regeneration following acoustic insult in three different species of birds. The battery of behavioral tests consists of 10 psychoacoustic measures including new, comprehensive measures of the shape of the auditory filter and the shape of the temporal window. These have never been measured before in birds. Psychoacoustic measures will be conducted in parallel with anatomical investigations on the same animals and animals exposed under identical conditions to assess changes occurring to hair cells, innervation patterns, stereocilia, tectorial membrane, and tegmentum vasculosum. Pilot data on quail have shown that the time course of hair cell regeneration at the basal end of the papilla coincides well with the time course of recovery from TTS. The comparative approach to this problem should provide insight into the anatomical changes important for recovery versus those that are not. Other behavioral experiments on the precision of vocal production and vocal learning will assess how well anatomical and psychoacoustic recovery is in supporting other natural, auditory-dependent behaviors important for communication. These experiments will provide the most comprehensive data base we know of on the functional consequences of replacing the peripheral sensory epithelium in a mature animal. These results will have relevance for the direction of future studies on regeneration of the nerve and sensory cells in the cochlea and their relevance for hearing. We expect these findings to also have relevance for any future efforts to replace the sensory epithelium in mammalian and, hopefully, the human cochlea.

The loss of hearing, and all that entails, has devastating consequences for human speech and language both in children and adults. The discovery of hair cell regeneration in birds has provided new hope of eventually restoring hearing in humans through hair cell regeneration. For this reason, it is important to know whether hearing is fully restored following hair cell regeneration in birds and, if not, what are the permanent, enduring effects on hearing and vocal production. Progress in this area has been challenging because, until recently, there is a complete absence of animal models for studying the effect of hearing loss on vocal output and vocal learning. The present research plan continues effort to understand the recovery of function following hear cell regeneration. Now we focus specifically on two species that provide quite different but unique opportunities for understanding the recovery of function. This new, more focused effort is the result of new and exciting findings from the last project period. First, we focus on understanding the relation between hearing recovery in budgerigars and the recovery in vocal precision and vocal learning. A new method for controlling vocal production and learning in an animal opens a whole new window on the study of hearing loss and vocal production. The second new focus is on the Belgian Waterslager canary. Our previous work confirmed that this specifies has an inherited hearing disorder due to missing or damaged hair cells on the basilar papilla, that they are constantly regenerating new hair cells, and that increasing the rate of regeneration can cure some of the inherited threshold shift in BWS canaries.

DESCRIPTION (provided by applicant): This application is a feasibility study for high impact research project to develop behavioral assays for studying hearing and more complex behaviors in the Zebrafish (Danio rerio). This is a feasibility study because an approach to study behavioral responses in zebrafish has never been attempted and, while preliminary evidence that these fish can be trained for relatively complex tasks is tantalizing, there is no guarantee of success. It is high impact because the zebrafish is an increasingly useful and important vertebrate model system for studies of vertebrate genetics. Most significantly, as new genes are discovered that has potential impact on behavior of growing and adult animals, it will be necessary to have ways to test and analyze the impact of the genes on sensory, motor, and central nervous system processes. However there are no highly quantifiable and reliable methods to assess the overall sensory and motor responses of these animals. The purpose of this application is to develop rigorous behavioral procedures for unrestrained, freely moving animals to permit access to such higher order processes as memory, attention, and learning. These kinds of processes can only be measured using psychophysical testing of the kind we propose to develop here. Over the course of this study we will develop an approach that leads to auto-shaping of animals so that they respond to a selected stimulus (a sound) by approaching a food source. The nature of the behavioral response will indicate whether the fish has or has not detected the signal, and we can thus assess many aspects of hearing and the auditory system. Once developed, the procedure will be applied to testing fishes with various mutations of the ear and auditory system to assess their effects on hearing in growing and adult animals. Moreover, once developed the basic procedure will have broad usefulness for assessment of other sensory, motor, and higher order functions.

DESCRIPTION (provided by applicant): The overall goals of the Core Center remain as before to: bring together 17 investigators working on different aspects of hearing and communication disorders, increase the efficiency and productivity of their individual efforts and ongoing collaborations, integrate investigators studying basic hearing mechanisms in animals with investigators studying human hearing impairment. This provides new and sometimes unique opportunities for creative and developing collaborations to reach fruition. The investigators participating in this application represent a broad range of hearing science from anatomy and physiology of hearing in insects to the psychoacoustics of complex sound perception in hearing impaired humans. Existing projects include sound localization in bats and birds, prey-predator interactions in insects and bats, hair cell regeneration in fish and birds, recovery of hearing and vocalizations in birds following hair cell regeneration, MIG imaging of language processes in humans, precision of time resolution in bats, birds, normal, hearing impaired, and aged humans, and the ontogeny of complex acoustic perception in insects, fish, birds, and humans. Taken together, this group of investigators and topics in hearing science is probably the most diverse in existence. The support of the P30 mechanism is essential in keeping a high level of interactive integrity and productivity.

Abstract: This proposal requests funds to continue enhancement of the human subject protection process at a large, diverse non-medical school university campus and to expand these developments to two neighboring public universities with similar human subject research activities. The University of Maryland College Park will continue development of software and educational tools begun during the first year of NIH support and will now share these developments with our collaborating institutions and, through our collaborations, initiate new and creative procedures for enhancing human subjects protection. Funds will be used to improve education and outreach within each Campus community, implement a continuous education procedure for all personnel involved in any aspect of human subjects research from IRB faculty and staff members to graduate and undergraduate student investigators, increase IRB quality by participating and hosting workshops on IRB best practices, increase IRB efficiency and discipline by organizing and clarifying the SOPs of each institution's IRB, institute an annual shared, cross-institution review of IRB processes, and facilitate certain aspects of the review process and its integration into sponsored research proposal tracking.

[unreadable] DESCRIPTION (provided by applicant): The loss of hearing, and all that entails, has devastating consequences for human speech and language both in children and adults. The discovery of hair cell regeneration in birds has provided new hope of eventually restoring hearing in humans through hair cell regeneration. For this reason, it is important to know whether hearing is fully restored following hair cell regeneration in birds and, if not, what are the permanent, enduring effects on hearing and vocal production. Progress in this area has been challenging because, until recently, there is a complete absence of animal models for studying the effect of hearing loss on vocal output and vocal learning. The present research plan continues effort to understand the recovery of function following hair cell regeneration. Now we focus specifically on two species that provide quite different but unique opportunities for understanding the recovery of function. This new, more focused effort is the result of new and exciting findings from the last project period. First, we focus on understanding the relation between hearing recovery in budgerigars and the recovery in vocal precision and vocal learning. A new method for controlling vocal production and learning in an animal opens a whole new window on the study of hearing loss and vocal production. The second focus is on the Belgian Waterslager Canary. Our previous work confirmed that this species has an inherited hearing disorder due to missing or damaged hair cells on the basilar papilla, that they are constantly regenerating new hair cells, and that increasing the rate of regeneration can "cure" some of the inherited threshold shift observed in BWS canaries. [unreadable] [unreadable]

This award is made through the Ethics Education in Science and Engineering solicitation (NSF 06-524). The project will develop a set of ethics courses and workshops that focus on graduate-student education, but also provide training on research integrity for postdoctoral associates and for new assistant professors that will enable these individuals to be better "role models" in research ethics for their graduate students. These courses will be developed first within the colleges of the Principal Investigators at the University of Maryland, College Park, using the extensive experience of the Principal Investigators in such courses. In the second year of the grant, the courses will be extended to the other science and engineering colleges and departments on the College Park campus. In the third year, the courses will be made available across the State of Maryland in the University System of Maryland. The courses will engage graduate students in actively solving real-world research-integrity problems, and the influence of the courses will be extended by training postdoctoral associates as ethics teachers. These trained teachers will later disperse across this country and abroad. The course for graduate students, Research Ethics, will include an introduction to the philosophy of ethics and value systems, and an introduction to the philosophy of science and how science is structured. Then it will discuss the issues that arise in trying to do "good Science" and to avoid bias in research, and the cross-checks against error and bias. Other topics will include animal subjects, human subjects, attribution and authorship, mentoring, intellectual property, and under-represented groups. A second course, Advanced Research Ethics, will be developed for postdoctoral associates and for graduate students who wish to obtain the Graduate Certificate in Research Ethics that will also be developed. This course will develop the course topics more deeply and will cover the pedagogy of ethics training. A new Research Ethics Workshop will be developed as a 4- to 6-hour one-day workshop for untenured faculty members in science and engineering, to introduce them to ethical concerns and to prepare them to mentor their own students on research integrity.
Intellectual merit: The project will engage graduate students and postdoctoral research associates in the analysis of the serious and complex ethical issues that face all scientists and engineers in the course of their careers.
Broader impacts: The project will produce (1) graduate students who know how to address ethical issues; (2) postdoctoral research associates who not only understand these issues, but know how to teach on these issues and can expand the impact of the project across Maryland, the United States, and beyond; (3) new faculty members who appreciate the importance of research integrity and can apply it in the training of their own students; and (4) extension of the courses developed at College Park to other campuses in Maryland.

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This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).

Studying activity of the human brain non-invasively is a major scientific challenge, yet it is essential for enhancing our understanding of the neural bases of action, emotion, and thought. A major technological advancement in studying the neural basis of behavior has been the development of functional magnetic resonance imaging (fMRI), a hemodynamic technique based on the tight coupling between neuronal activity and oxygenated blood flow. fMRI is a powerful tool for non-invasively measuring local changes in the brain with high spatial resolution (~1 mm) in the blood oxygen level dependent (BOLD) signal. Additionally, structural imaging using MRI can characterize volumetric differences in brain tissue and specify major pathways of neural processing and transmission. These approaches can be combined with other neuroimaging data examining the temporal dynamics of brain activity, to establish a more complete understanding of the human brain and the neural processes underlying human cognition, action, and emotion.

A state-of-the-art 3-Tesla Magnetic Resonance Imaging (MRI) scanner will provide access to this powerful technology to the University of Maryland College Park community for studying human brain activity. The MRI scanner will serve as the centerpiece of the Brain Imaging Center at Maryland (BICAM) and will transform the research and educational environment at the University of Maryland. The scanner will provide the foundation for research in cognitive and affective neuroscience, with specific foci on human development, attention and memory, decision making and risk, motor-control, and language and communication. The center will also create opportunities for innovations in signal processing and magnetic resonance physics. The center and its shared instrumentation will foster an intensive learning environment through the integration of research and education within the University of Maryland and through its partnerships in the local community. The MRI scanner will enhance graduate and undergraduate education through directed research projects, courses with a hands-on focus in functional neuroimaging, and accessibility to students from underrepresented groups. The center will also sponsor a summer institute in developmental cognitive neuroscience which will bring experts in the study of brain development and neuroimaging to the University of Maryland.

BICAM is part of the Neuroscience and Cognitive Science (NACS) program at the University of Maryland. This program consists of faculty from traditional behavioral and neuroscience departments such as Psychology, Human Development, Linguistics, Hearing and Speech, and Kinesiology, as well as faculty from Computer Science, Physics, Applied Mathematics, and Electrical and Computer Engineering with expertise in imaging, signal processing, and the physical basis of magnetic resonance technology. Acquisition of the new scanner will lead to broad interdisciplinary collaboration in areas of the basic physical and behavioral sciences with the goal of understanding the neural bases of behavior.