Full Text PA-96-035 CHEMICAL SENSES: NEUROTRANSMITTERS AND NEUROMODULATORS NIH GUIDE, Volume 25, Number 10, March 29, 1996 PA NUMBER: PA-96-035 P.T. 34 Keywords: 0775017 Neurotransmitters Receptors National Institute on Deafness and Other Communication Disorders National Institute on Aging PURPOSE The National Institute on Deafness and Other Communication Disorders (NIDCD) and the National Institute on Aging (NIA) invite grant applications for the support of research fundamental to understanding the neurochemistry of pathways in the olfactory and gustatory systems throughout the life span. This research includes the identification and characterization of the neurotransmitters, neuromodulators, receptors, and secondary messengers throughout the chemosensory systems. 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 Program Announcement (PA), Chemical Senses: Neurotransmitters and Neuromodulators, is related to the priority areas of diabetes and chronic disabling conditions and special population objectives. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-11474-0 or Summary Report: Stock No. 017-001-11473-1) 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 or organizations in foreign countries are not eligible for First Independent Research Support Transitions (FIRST) (R29) awards. MECHANISM OF SUPPORT The support mechanisms for grants in this area will be the individual investigator-initiated research grant (R01) and the First Independent Research Support and Transition (FIRST) (R29) Award. RESEARCH OBJECTIVES The physiology and chemistry of the neural circuits of the olfactory and gustatory systems have been extensively studied, and certain chemically distinct synapses in these chemosensory systems have been identified. The relation of these findings to synaptic function and to central processing of chemosensory information is far from fully understood. There is evidence that the levels of neural activity within olfactory structures can influence the synthesis of transmitter and trophic substances and the strength of synaptic connections. It is not known how these changes alter the processing of olfactory information. Little is yet known about the transmitters and their receptors at the principal relays throughout the chemosensory pathways; the transmitters at the receptor cell-nerve interfaces in the chemosensory systems have not been unequivocally identified. The neurochemistry of the central olfactory system poses a challenging issue because of the wide variety of transmitter substances represented, particularly in the olfactory bulb. A better understanding of the mechanisms of neurotransmission in the chemosensory systems is possible through the application of contemporary tools such as biochemical and molecular probes, brain slice and organotypic culture preparations, transgenic animal models, electrophysiologic recording in anesthetized and in freely moving animals, and computational modeling. These important tools have had only limited use in studies of the neurochemistry of the chemosensory systems; their use in investigations of the transmitters and receptors of the chemosensory systems holds promise for the eventual development of effective prevention and treatment of chemosensory disorders. The National Institute on Deafness and Other Communication Disorders (NIDCD) and the National Institute on Aging (NIA) are interested in a broad range of mechanistic studies that will elucidate the neurochemistry of the pathways of the olfactory and gustatory systems over the life span. This research includes the identification and characterization of the neurotransmitters, neuromodulators, receptors, and second messengers throughout the chemosensory systems. Multidisciplinary studies of neurotransmitter and neuromodulatory mechanisms relevant to structure-function relations are encouraged as are collaborative efforts that lead to the integration of information from levels spanning the molecular to the behavioral. Collaboration is encouraged among investigators, including molecular and cell biologists, pharmacologists, and other scientists who are using novel approaches to study the neurochemistry of sensory systems. Investigators are encouraged to address pivotal issues in the chemical senses in response to this Program Announcement and to utilize innovative methods and approaches to address them. Research issues, methods, and approaches in the chemical senses might include, but are not limited to, those below. Research issues o Identification and characterization of the transmitters at the receptor cell-nerve interface in the olfactory and gustatory systems. o Molecular properties of amino acid receptors in the chemosensory systems. o The role of transmitters in the regulation of neuronal growth, plasticity, and survival. o Neuron-glial communication. o The role of simple gases, such as carbon monoxide, in neurotransmission. o Functional significance of neurochemical and molecular diversity of subsets of neurons in the olfactory bulb. o Age-related changes in transmitter levels and transmitter-receptor relationships within the chemosensory systems. o Age-related mechanisms governing transmitter responses to injury of the chemosensory systems. o Ability of neurotoxins to affect the levels of transmitters and their receptors as a function of aging. o Mechanisms whereby an age-related change in one neuroactive substance can interact with and alter the levels of other neuroactive substances in the chemosensory systems. Methods and approaches: o Biochemical and molecular probes to identify and characterize the neurotransmitters and receptors involved in the central processing of chemosensory information. o Electrophysiologic and imaging techniques that are sufficiently sensitive to analyze neural circuit activity. o Confocal imaging and photolytic activation of compounds as dual probes of transmitter and synaptic function in brain slices. o Transgenic animals with altered transmitters and receptors. o Use of agonists and antagonists to investigate transmitter function. 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 was reprinted in the Federal Register of March 28, 1994 (FR 59 14508-14513) to correct typesetting and errors in the earlier publication, and reprinted in the NIH GUIDE FOR GRANTS AND CONTRACTS of March 18, 1994, Volume 23, Number 11. 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 Applications are to be submitted on the grant application form PHS 398 (rev. 5/95) and will be accepted at the standard application deadlines as indicated in the application kit. Applications kits are available at most institutional offices of sponsored research and may be obtained from the Grants Information Office, Office of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/710-0267, email: ASKNIH@odrockm1.od.nih.gov. The title and number of the program announcement must be typed in Section 2 on the face page of the application. Applications for the FIRST Award (R29) must include at least three sealed letters of reference attached to the face page of the original application. FIRST Award (R29) applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. The completed original application 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 Upon receipt, applications will be reviewed for completeness by the DRG. Incomplete applications will be returned to the applicant without further consideration. Applications that are complete 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 may undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of all applications under review, will be discussed, assigned a priority score, and receive a second level review by the appropriate national advisory council or board. Review Criteria o scientific, technical, or medical significance and originality of proposed research; o appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; o qualifications and research experience of the Principal Investigator and staff, particularly, but not exclusively, in the area of the proposed research; o availability of the resources necessary to perform the research; o appropriateness of the proposed budget and duration in relation to the proposed research; and o 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. The Initial review group will also examine the provisions for the protection of human subjects and animal welfare and the safety of the research environment. AWARD CRITERIA Applications will compete for available funds with all other applications assigned to that Institute. The following will be considered in making funding decisions: quality of the proposed project as determined by peer review and availability of funds. INQUIRIES Written and telephone inquiries concerning this PA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Jack Pearl, 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) 402-3464 FAX: (301) 402-6251 Email: Jack_Pearl@nih.gov Judith A. Finkelstein, Ph.D. Neuroscience and Neuropsychology of Aging Program National Institute on Aging Gateway Building, Suite 3C307 7201 Wisconsin Avenue, MSC 9205 Bethesda, MD 20892-9205 Telephone: (301) 496-9350 FAX: (301) 496-1494 Email: FinkelsJ@gw.nia.nih.gov Direct inquiries regarding fiscal matters to: Sharon Hunt Division of Extramural Activities National Institute on Deafness and Other Communication Disorders Executive Plaza South, Room 400-B 6120 Executive Boulevard - MSC 7180 BETHESDA, MD 20892-7180 Telephone: (301) 402-0909 FAX: (301) 402-1758 Email: SH79F@nih.gov Joseph Ellis, Chief Office of Extramural Affairs National Institute on Aging Gateway Building, Suite 2N212 7201 Wisconsin Avenue, MSC-9205 Bethesda, MD 20892-9205 Telephone: (301) 496-1472 FAX: (301) 402-3672 Email: EllisJ@gw.nia.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance Nos. 93.173 and 93.866. 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 the 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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