Lynn Churchill - US grants

Dopamine and opioid receptors in the nucleus accumbens are, at least partially, responsible for increases in locomotor activity following the administration of cocaine or opioids. Although the opioid system does not depend upon dopamine for its actions, the depletion of dopamine will augment opioid-induced locomotor activity. The neurochemical basis for this peptide-amine interaction has not yet been elucidated. The coupling of dopamine and opioid receptors in the same postsynaptic neurons may result in an upregulation of opioid receptors in response to dopamine depletion. Preliminary data support this hypothesis. The anatomical localization of any increases in opioid receptor affinity or number will be analyzed by quantitative receptor autoradiography. Another hypothesis is that the dopamine and opioid receptors share a second messenger or ion channel whose activity is enhanced by the dopamine depletion. Modification in the number of Ca+2-activated K+ channels, guanine nucleotide binding proteins or alterations in the opioid inhibition of dopamine-stimulated adenylate cyclase after dopamine depletion might enhance the response of the cell to opioids. The number of Ca+2-activated K+ channels will be determined by specific binding of the bee venom toxin, [125I]apamin. The number of guanine nucleotide binding (Go or Gi) proteins will be measured by [32P]ADP-ribosylation in the presence of pertussis toxin. Opioid agonist inhibition of dopamine-sensitive adenylate cyclase will be analyzed in plasma membrane fractions from nucleus accumbens. If alterations in these neurochemical parameters occur 10 days after the dopaminergic lesion,, then a time course of dopamine depletion will be correlated with the neurochemical alterations. To further evaluate the behavioral role of the Ca+2-activated K+ channels and of guanine nucleotide binding proteins, the opioid-induced augmentation in locomotor activity after dopamine depletion will be evaluated after apamin or pertussis toxin injections into the nucleus accumbens. Understanding the neurochemical basis for these dopamine-opioid interactions will provide mechanistic information in drug abuse situations where the use of cocaine and opioids has been combined.

Dopamine and opioid receptors in the nucleus accumbens are, at least partially, responsible for increases in locomotor activity following the administration of cocaine or opioids. Although the opioid system does not depend upon dopamine for its actions, the depletion of dopamine will augment opioid-induced locomotor activity. The neurochemical basis for this peptide-amine interaction has not yet been elucidated. The coupling of dopamine and opioid receptors in the same postsynaptic neurons may result in an upregulation of opioid receptors in response to dopamine depletion. Preliminary data support this hypothesis. The anatomical localization of any increases in opioid receptor affinity or number will be analyzed by quantitative receptor autoradiography. Another hypothesis is that the dopamine and opioid receptors share a second messenger or ion channel whose activity is enhanced by the dopamine depletion. Modification in the number of Ca+2-activated K+ channels, guanine nucleotide binding proteins or alterations in the opioid inhibition of dopamine-stimulated adenylate cyclase after dopamine depletion might enhance the response of the cell to opioids. The number of Ca+2-activated K+ channels will be determined by specific binding of the bee venom toxin, [125I]apamin. The number of guanine nucleotide binding (Go or Gi) proteins will be measured by [32P]ADP-ribosylation in the presence of pertussis toxin. Opioid agonist inhibition of dopamine-sensitive adenylate cyclase will be analyzed in plasma membrane fractions from nucleus accumbens. If alterations in these neurochemical parameters occur 10 days after the dopaminergic lesion,, then a time course of dopamine depletion will be correlated with the neurochemical alterations. To further evaluate the behavioral role of the Ca+2-activated K+ channels and of guanine nucleotide binding proteins, the opioid-induced augmentation in locomotor activity after dopamine depletion will be evaluated after apamin or pertussis toxin injections into the nucleus accumbens. Understanding the neurochemical basis for these dopamine-opioid interactions will provide mechanistic information in drug abuse situations where the use of cocaine and opioids has been combined.

9454691 Thomas Network Montana is a collaborative, systemic research and development project constituting Montana's response to NSF's Networking Infrastructure for Education (NIE) RFP #94-5. The goal of the NSF/NIE program is to build synergy between technology and educational researchers, developers, and implementers in the use of network and telecommunications technologies in education, with a particular focus on the development of flexible, sustainable approaches to network infrastructure. This proposal seeks funding for a one-year planning grant aimed at developing a systemic approach to K-16 networking in Montana. The partners in this enterprise will include teachers, administrators, and researchers from the state's educational system, leaders in state government, and individuals from a variety of community, professional, and private sector organizations. Commitments of talent and resources from all partners will be focused on the development of a lasting infrastructure capable of supporting the development of a variety of educational telecommunications services. Specifically, at the end of the planning period, the Network Montana Project will: 1. Define a state-wide coalition of partners from academia, government, and the private sector responsible for directing a wide variety of K-16 educational networking activities during the period of NSF/NIE funding and in subsequent projects; 2. Make use of Montana Information Services Division (ISD) leased lines and Big Sky Telegraph capabilities to pilot Internet access for select K-12 schools and their local libraries; 3. Encourage and facilitate long-term partnerships with computer equipment and software manufacturers, aerospace industries, and other private sector organizations interested in educational reform; 4. Facilitate cooperative partnerships with NASA, NOAA, the U.S. Geological Survey and other national and international scientific organizatio ns; 5. Cooperate with and support a number of nationally significant mathematics and science education projects already underway in Montana; 6. Focus on the development of educational and informational resources deliverable over the Internet and of interest to Montanans of all ages, and; 7. Develop a position paper on the networking implications for mathematics and science education reform. The foundation of the Network Montana Project is cooperation and collaboration. All major organizations and institutions involved with mathematics education, science education, telecommunications, or networking across Montana are participants in this planning grant. Industry support from TCI, Digital Equipment Corporation, Microsoft, Square One TV and others also plays a significant role.

Churchill 95-54251 Network Montana Project (NMP) will focus on the development of flexible, sustainable approaches to a systemic educational network infrastructure. The partners in this enterprise will include teachers, administrators, and researchers from the state's educational system, leaders in state government, and individuals from a variety of community, professional, and private sector organizations. Commitments of talent and resources from all partners will be focused on the development of a lasting infrastructure capable of supporting the development of a variety of educational telecommunications services. This proposal seeks funding for a three year grant aimed at developing a systemic approach to K-16 networking in Montana that: 1. Builds and maintains a state-wide coalition of partners from academia, government, and the private sector responsible for directing a wide variety of K16 educational networking activities during the period of NSF/NIE funding and in subsequent projects; 2. Supports and enhances a number of nationally significant systemic mathematics and science education reform projects; 3. Integrates multimedia network-based materials and delivery systems into mathematics and science instruction to enhance access and usability of many scientific resources. 4. Investigates adaptations of educational and informational telecommunications required to serve populations with special needs including those that may be visually or hearing impaired; 5. Develops a workable community networking model that is feasible in a low population density environment, promoting teleliteracy for rural citizens to enhance their involvement with lifelong learning, entrepreneurship and local/state governance.

With this award, The University of Montana will join over 150 other
research universities who are engaged in advanced high performance
networking, the Next Generation Internet initiative, and the consortium of
Internet2 universities. The award provides Montana with $350,000, an amount
they will more than match, so that they can establish their advanced
network link through a gigapop in Seattle at the University of Washington.
These network connections are supported by NSF in order to enable science
and research uses at the universities. Montana has a number of strong
research activities and programs related to the biological sciences,
mining, forestry, land use, and management of natural resources. Their
collaborations with other universities in the region and throughout the
nation, as well as other support from NASA and DOE, will be greatly served
by this new networking facility.

Physical and intellectual infrastructures in computational sciences will be developed as part of a long-term effort to stimulate new collaborations and research opportunities utilizing high-performance computing as a necessary tool among a diverse group of researchers. The physical infrastructure will consist of a low-cost cluster of Linux workstations for education, training, and development of activities that utilize high-performance computing, coupled with partnerships with the Arctic Region Supercomputing Center, the North Carolina Supercomputing Center, and the University of Texas Health Science Center at San Antonio. Most importantly, intellectual infrastructure will also be developed that provides a highly proactive environment towards training and aiding researchers in various disciplines to utilize high-performance computing methods to enhance their existing research programs and to establish new research approaches. It is anticipated that the project will result in a physical computational infrastructure, a center of expertise in computational infrastructure, a center of expertise in collaborative computational sciences, and a catalyst for obtaining sustained funding from a wide range of resources. Such environment, the Northern Rockies Center for Applied Computational Science, will act as a focal point to stimulate numerous opportunities for researchers to branch out in new directions that benefit with increased computational literacy.

DESCRIPTION (adapted from applicant's abstract): Excessive food intake and peripheral infectious challenge are associated with increases in non-rapid eye movement sleep (NREMS). The vagus and vagal-induced upregulation of cytokines seems to mediate these sleep responses, in part. However, whether action potentials in the vagus induce cytokine upregulation in the brain and the central circuit tying vagal afferents to increased sleep and cytokine production remains unknown. Vagal-mediated intracerebral increases in cytokine mRNA levels have been observed in the brainstem and hypothalamus, two areas implicated in regulating NREMS. Neuroanatomical localization of the cell types involved in these increased cytokine mRNA levels are evaluated in a series of experimental tests. The following hypotheses are evaluated: (1) action potentials in vagal afferents are responsible and (2) the neural circuitry from the vagal afferent projection to the nucleus of the solitary tract through the lateral parabrachial nucleus to the anterior hypothalamus and medial preoptic area is responsible. Finally, the hypotheses that neurons within this circuitry are upregulating their cytokine mRNA levels in a vagal-mediated fashion is tested by retrogradely labeling specific neural projections. Mapping the vagal-mediated intracerebral cytokines within the brainstem and hypothalamus will provide new insights into the functional neuroanatomy that underlies the regulation of NREMS.

DESCRIPTION (adapted from applicant's abstract): Excessive food intake and peripheral infectious challenge are associated with increases in non-rapid eye movement sleep (NREMS). The vagus and vagal-induced upregulation of cytokines seems to mediate these sleep responses, in part. However, whether action potentials in the vagus induce cytokine upregulation in the brain and the central circuit tying vagal afferents to increased sleep and cytokine production remains unknown. Vagal-mediated intracerebral increases in cytokine mRNA levels have been observed in the brainstem and hypothalamus, two areas implicated in regulating NREMS. Neuroanatomical localization of the cell types involved in these increased cytokine mRNA levels are evaluated in a series of experimental tests. The following hypotheses are evaluated: (1) action potentials in vagal afferents are responsible and (2) the neural circuitry from the vagal afferent projection to the nucleus of the solitary tract through the lateral parabrachial nucleus to the anterior hypothalamus and medial preoptic area is responsible. Finally, the hypotheses that neurons within this circuitry are upregulating their cytokine mRNA levels in a vagal-mediated fashion is tested by retrogradely labeling specific neural projections. Mapping the vagal-mediated intracerebral cytokines within the brainstem and hypothalamus will provide new insights into the functional neuroanatomy that underlies the regulation of NREMS.