A fundamental goal in neurobiology is understanding the relationship between structure and function. This proposal consists of two inter-related interdisciplinary projects: (a) defining the anatomical organization of the cholinergic afferent connections to the central biogenic amine neuron systems, and (b) investigation a now well-defined function of the central noradrenergic system--the regulation of cerebral capillary permeability. In order to study the anatomical interactions of the central cholinergic system, specific anti-sera to choline acetyltransferase were prepared and a method developed for the simultaneous localization of the cholinergic system and the three biogenic amine systems using dual label immunohistochemistry. A large pontomesencephalic cholinergic nucleus has been shown to make afferent connections with neurons containing all three biogenic amines. It is hypothesized that this cholinergic nucleus integrates a wide variety of ascending and descending information with which it coordinates the activity of the major amine systems. The present thrust of the anatomical project is to precisely define and map the interconnections between this cholinergic nucleus and the three biogenic amine systems. Previous anatomical work has defined possible neuronal circuits which may mediate physiologically induced changes in vascular permeability in response to increased blood pressure and osmolarity. These circuits will be tested using a combination of physiological and pharmacological techniques. The receptors mediating these responses will be defined. The structure and function of the central biogenic amine systems has many clinical implications. Most centrally acting drugs effect this system either directly or indirectly. A clear understanding of the action of these drugs has been hampered by the lack of a well- defined and measureable function to study. Our discovery that this system regulates capillary permeability to water has provided such a function. In addition, this finding has broadened the concept of the blood-brain barrier.
The aims of the present proposal is to define the anatomical circuits utilized in permeability regulation and to determine the pharmacological means of manipulation this function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS012311-17
Application #
3394782
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1987-07-01
Project End
1992-12-31
Budget Start
1991-01-01
Budget End
1992-12-31
Support Year
17
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Oakman, S A; Faris, P L; Cozzari, C et al. (1999) Characterization of the extent of pontomesencephalic cholinergic neurons' projections to the thalamus: comparison with projections to midbrain dopaminergic groups. Neuroscience 94:529-47
Oakman, S A; Faris, P L; Kerr, P E et al. (1995) Distribution of pontomesencephalic cholinergic neurons projecting to substantia nigra differs significantly from those projecting to ventral tegmental area. J Neurosci 15:5859-69
Chedotal, A; Umbriaco, D; Descarries, L et al. (1994) Light and electron microscopic immunocytochemical analysis of the neurovascular relationships of choline acetyltransferase and vasoactive intestinal polypeptide nerve terminals in the rat cerebral cortex. J Comp Neurol 343:57-71
Chedotal, A; Cozzari, C; Faure, M P et al. (1994) Distinct choline acetyltransferase (ChAT) and vasoactive intestinal polypeptide (VIP) bipolar neurons project to local blood vessels in the rat cerebral cortex. Brain Res 646:181-93
Iadecola, C; Faris, P L; Hartman, B K et al. (1993) Localization of NADPH diaphorase in neurons of the rostral ventral medulla: possible role of nitric oxide in central autonomic regulation and oxygen chemoreception. Brain Res 603:173-9
Wozniak, D F; Stewart, G R; Finger, S et al. (1989) Comparison of behavioral effects of nucleus basalis magnocellularis lesions and somatosensory cortex ablation in the rat. Neuroscience 32:685-700
Wozniak, D F; Stewart, G R; Finger, S et al. (1989) Basal forebrain lesions impair tactile discrimination and working memory. Neurobiol Aging 10:173-9
Wong, Y H; Kalmbach, S J; Hartman, B K et al. (1987) Immunohistochemical staining and enzyme activity measurements show myo-inositol-1-phosphate synthase to be localized in the vasculature of brain. J Neurochem 48:1434-42
Rubin, E H; Preskorn, S H; Hartman, B K (1986) The role of the central adrenergic system in the regulation of the cerebromicrocirculation. Basic and clinical implications. Ann N Y Acad Sci 462:224-31
Stewart, G R; Price, M; Olney, J W et al. (1986) N-methylaspartate: an effective tool for lesioning basal forebrain cholinergic neurons of the rat. Brain Res 369:377-82