Ongoing collaborations between neuroscientists at the St. Louis University School of Medicine, Medical College of Ohio, Henry Ford Foundation, University of Iowa, and Washington University School of medicine will continue to address mechanisms responsible for normal developmenta nd injury-induced reorganization in mammalian sensory systems. The central trigeminal (V) representations of the rodent whiskers (barrels) are being used as a model. Seven projects will test hypotheses pertaining to: 1) What makes whisker-related patterns? 2) What maintains whisker-related patterns? 3) What determines orderly axon target selectiona nd ingrowth patterns? 4) What determines orderly development of dendritic trees? 5) How do """"""""modulatory"""""""" pathways develop and impact on the barrel neuraxis? A CORE provides morphometry, electron microscopy, tissue culture, animal and administrative facilities, and ensures timely communication between projects and external review. The 1st project will use organotypic tissue culture a d tract tracing methods to uncover mechanisms of primary afferent target selection and ingrowth. The next project will use anatomical labeling, infraorbital nerve injury and axoplasmic transport blocking methods to reveal mechanisms responsible for potnatal pattern maintenance in the V brainstem complex. The next project will test the hypothesis that whisker-related pattern formation occurs as a direct result of neurotrophically regulated, naturally occurring cell death in the V ganglion. Anatomical and electrophysiological methods will be used after various fetl neurotrophin augmentation regimens to determine mechanisms responsible for neurotrophin-induced changes in V primary afferent projection pattrns. The next project focusses on the normal development of, and actions of neurotrophins upon, cells in V nucleus principalis. The next project will use anatomical and electrophysiological methods to examine the development of thalamocortical neurons and the role of specified afferents and target factors in axodendritic arborization. The next project will test the hypothesis that serotonin influences thalamocortical development by acting at 5HT ib receptors located on the terminals of thalamic axons to presynaptically inhibit thalamocortical synaptic transmission; this action modulates activity-dependent process involved in the development of terminal arbors. The last project offers anatomical and pharamcological experiments to assess the normal development, specificity and activity-related plasticity of the somatosensory cortical projections to the thalamus adnd V brainstem complex. These studies will reveal general principles guiding somatosensory development in humans because humans also have somatotopically parcellated, barrel-like aggregations in the V brainstem nucleus. We will also provide new information ont he biological actions of neurotrophic factors that may be of future use in treating certain neuropathic disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Program Projects (P01)
Project #
2P01DE007734-10
Application #
2129887
Study Section
Special Emphasis Panel (ZDE1-PW (09))
Project Start
1989-12-01
Project End
2000-02-14
Budget Start
1995-02-15
Budget End
1996-02-14
Support Year
10
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Washington University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Jacquin, Mark F; Arends, Joop J A; Renehan, William E et al. (2015) Whisker-related circuitry in the trigeminal nucleus principalis: Topographic precision. Somatosens Mot Res 32:8-20
Xiang, Chuanxi; Arends, Joop J A; Jacquin, Mark F (2014) Whisker-related circuitry in the trigeminal nucleus principalis: ultrastructure. Somatosens Mot Res 31:141-51
Pluto, Charles P; Chiaia, Nicolas L; Rhoades, Robert W et al. (2005) Reducing contralateral SI activity reveals hindlimb receptive fields in the SI forelimb-stump representation of neonatally amputated rats. J Neurophysiol 94:1727-32
Genc, Baris; Ulupinar, Emel; Erzurumlu, Reha S (2005) Differential Trk expression in explant and dissociated trigeminal ganglion cell cultures. J Neurobiol 64:145-56
Vadivelu, Sudhakar; Platik, Marina M; Choi, Luke et al. (2005) Multi-germ layer lineage central nervous system repair: nerve and vascular cell generation by embryonic stem cells transplanted in the injured brain. J Neurosurg 103:124-35
Gandhi, Rohan; Ryals, Janelle M; Wright, Douglas E (2004) Neurotrophin-3 reverses chronic mechanical hyperalgesia induced by intramuscular acid injection. J Neurosci 24:9405-13
McDonald, John W; Becker, Daniel; Holekamp, Terrence F et al. (2004) Repair of the injured spinal cord and the potential of embryonic stem cell transplantation. J Neurotrauma 21:383-93
Genc, Baris; Ozdinler, P Hande; Mendoza, April E et al. (2004) A chemoattractant role for NT-3 in proprioceptive axon guidance. PLoS Biol 2:e403
Ulupinar, Emel; Unal, Nedim; Erzurumlu, Reha S (2004) Morphometric analysis of embryonic rat trigeminal neurons treated with different neurotrophins. Anat Rec A Discov Mol Cell Evol Biol 277:396-407
Wright, Douglas E; Ryals, Janelle M; McCarson, Kenneth E et al. (2004) Diabetes-induced expression of activating transcription factor 3 in mouse primary sensory neurons. J Peripher Nerv Syst 9:242-54

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