Full Text PA-96-009 CENTRAL AUDITORY SYSTEM PLASTICITY IN ADULTS NIH GUIDE, Volume 24, Number 41, December 1, 1995 PA NUMBER: PA-96-009 P.T. 34 Keywords: Hearing National Institute on Deafness and Other Communication Disorders PURPOSE The National Institute on Deafness and Other Communication Disorders (NIDCD) invites applications for the support of research on central auditory system plasticity in adults. Such studies may lead to a better understanding of normal brain function and development as well as an explanation of the recovery of auditory function sometimes seen following injury to the auditory system. In addition, these studies have the potential to reveal how auditory learning occurs, including that often seen following cochlear implantation. Findings from these studies may also guide the development of therapies for recovery of function following brain injuries, diseases, and disorders that affect auditory perception. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This PA, Central Auditory System Plasticity in Adults, is related to the priority area of diabetes and chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of state and local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible for First Independent Research Support and Transition (FIRST) (R29) awards. Applications from minority individuals, women, and individuals with disabilities are encouraged. MECHANISM OF SUPPORT The support mechanism for grants in this area will be the individual investigator-initiated research project grant (R01) and the FIRST (R29) award. RESEARCH OBJECTIVES Background Change in synaptic strength has long been invoked as a possible mechanism underlying learning and memory throughout the lifespan. While it has also been recognized that major features of functional organization of neural structures, such as representation of the body surface in somatosensory cortex, are modifiable during specific periods of development, these maps were considered to be "hard-wired" in adults and incapable of change. Over the last decade, however, studies of several sensory- and motor-related regions of neocortex have revealed that such maps undergo significant reorganization in response to injury and learning in adults. Despite the potential significance that such research holds for understanding a host of basic and clinical issues regarding auditory function, few studies of plasticity have been carried out in the mature auditory system. This program announcement (PA) encourages research on plasticity in the adult auditory system at any level(s) of biological organization, from the level of the molecule to behavior, and at any processing station(s), from the cochlea to higher-order areas of auditory cortex, and beyond. Changes in the organization of representations of the periphery at the cortical level have been demonstrated following cochlear damage, retinal damage, limb amputation, and disruption of sensory innervation of the skin in adults. Following such peripheral perturbations, regions of cortex that are deprived of normal input do not become "silent," but typically respond to the remaining (usually adjacent) sensory inputs that are still intact. This often results in a shrinkage or elimination of the representation of the perturbed periphery and an enlargement of the representation of the intact periphery. Although most investigations of this type have examined changes in neocortex, subcortical structures have also been studied using these experimental approaches. The effects of learning on sensory cortex have been documented in the auditory system. For example, frequency receptive fields of neurons in the adult primary auditory cortex can be modified to that of a conditioned stimulus using classical conditioning paradigms. These changes have been shown to develop rapidly, are highly specific, can last indefinitely, and occur for different learning paradigms. Subcortical plasticity in the adult animal is also seen in changes in the receptive fields of midbrain neurons during sound localization tasks. While it is accepted that the central nervous system remains plastic throughout the lifespan, the mechanisms underlying this plasticity are unclear. The time course for these changes is variable, and may be due to the growth of axons and the formation of new connections over long distances or due to alterations in synaptic strength and the "unmasking" or activation of subthreshold pathways. The involvement of different forms of synaptic change, such as short- and long-term depression and potentiation, appears to vary for different brain regions. This suggests that, although the brain has a variety of means of modifying synapses, all regions do not achieve these modifications in the same way. The molecular mechanisms underlying the various forms of synaptic change also vary across brain regions. There are many possible explanations for these differences, but it is clear that understanding the implications of adult plasticity for auditory function would be best served by examining this specifically in the auditory system. The roles of drug and nondrug therapies for the recovery of function following peripheral or central injury or disease and their relationships to plastic changes in the central nervous system are under investigation. For example, the ability of nerve growth factors to enhance functional brain recovery following stroke is being studied in humans. The role of physical therapy in the recovery of motor function and observed changes in motor cortical regions is also being examined. Studies of such therapies offer great promise for improving and speeding recovery from brain and sensory and motor system diseases and disorders, but have thus far received little attention in the auditory system. Research Goals and Scope Current research related to central auditory plasticity in adults is yielding exciting insights into the nature of this phenomenon, and promises to improve understanding of the auditory system. Research on adult plasticity of the auditory system is, however, still in its infancy, and many areas need to be explored. Fulfilling the ultimate hope that this phenomenon will be harnessed to improve the lives of those with hearing impairment depends upon a sophisticated understanding of plasticity of the adult auditory system. The purpose of this PA is to encourage applications for research on topics such as, but not limited to, the following: o determination of the limits (e.g., time course, neural distance, effects of training) of central auditory nervous system plasticity following damage to the auditory system; o determination of the limits (e.g., time course, neural distance, effects of training) of central auditory nervous system plasticity induced by auditory training and deprivation; o elucidation of the relationship between central auditory nervous system plasticity and functional recovery following damage to the auditory system; o comparison of the nature and extent of plasticity occurring at different processing stations of the central auditory nervous system; o identification and characterization of the various forms of synaptic change (e.g., long- and short-term potentiation and depression) involved in central auditory nervous system plasticity; o identification and characterization of candidate neurochemical mechanisms for central auditory nervous system plasticity; and o development of new or improvement of existing therapies (both drug and nondrug) for the recovery of function following damage to the auditory system or for the enhancement of plasticity in the intact auditory system. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Women in Study Populations, and Concerning the Inclusion of Minorities in Study Populations), which have been in effect since 1990. The new policy contains some provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 28, 1994 (FR 59 14508- 14513) and reprinted in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 5/95) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 6701 Rockledge Drive, Room 3032, MSC 7762, Bethesda, MD 20892-7762, telephone 301/710-0267, email: girg@drgpo.drg.nih.gov. The completed original and five legible copies must be sent or delivered to: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) REVIEW CONSIDERATIONS Applications will be evaluated for scientific and technical merit by an appropriate peer review group convened in accordance with NIH peer review procedures. As part of the initial merit review, all applications will receive a written critique and undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed, assigned a priority score, and receive a second level review by the appropriate national advisory council or board. The review criteria are: scientific, technical, or medical significance and originality of proposed research; appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; qualifications and research experience of the Principal Investigator and staff, particularly, but not exclusively, in the area of the proposed research; availability of the resources necessary to perform the research; appropriateness of the proposed budget and duration in relation to the proposed research; and adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. AWARD CRITERIA Applications will compete for available funds with all other applications assigned to that Institute or Center. The following will be considered in making funding decisions: quality of the proposed project as determined by peer review; availability of funds; and program priorities among research areas of the program announcement. INQUIRIES Written, telephone, and email inquiries concerning this PA are encouraged; the opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding scientific content to: Lynn E. Huerta, Ph.D. Division of Human Communication National Institute on Deafness and Other Communication Disorders Executive Plaza South, Room 400-C 6120 Executive Boulevard MSC 7180 Bethesda, MD 20892-7180 Telephone: (301) 402-3458 FAX: (301) 402-6251 Email: Lynn_Huerta@nih.gov Direct inquiries regarding fiscal matters to: Sharon Hunt Grants Management Office National Institute on Deafness and Other Communication Disorders 6120 Executive Boulevard, Room 400-B, MSC 7180 Bethesda, MD 20892-7180 Telephone: (301) 402-0909 FAX: (301) 402-1758 Email: Sharon_Hunt@nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.173. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103- 227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. .
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