Single neurons in the mammalian central nervous sytem (CNS) contain more than one neurotransmitter. Since environmental signals alter neurotransmitter gene expression, the existence of multiple neurotransmitter systems within single neurons increases the potential complexity of neuronal responses. We, therefore, plan to study the coordinate regulation of three neurotransmitters known to be co-localized in neurons of the ventral medualla of mouse and rat brain: the """"""""classical"""""""" monoamine transmitter serotonin (5 - HT), the peptide transmitters substance P (SP) and thyrotropin-releasing hormone (TRH). cDNA probes for the SP and TRH preprohormones are available. The application of molecular biological approaches to the problem of neurotransmitter expression will allow us to examine these issues at the level of gene expression. Armed with the tools of both neuropharmacology and molecular biology, then, we plan 1) to determine whether pharmacological alterations in serotonin levels affect the expression of co-localized peptide neurotransmitters, and 2) determine whether the observed changes in peptide expression are the result of altered serotonergic neurotransmission. Studies in vivo will be extended by studies performed in organotypic tissue culture where the microenvironment can be more carefully controlled.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH043365-02
Application #
3382846
Study Section
Neurosciences Research Review Committee (BPN)
Project Start
1988-08-01
Project End
1991-07-31
Budget Start
1989-08-01
Budget End
1990-07-31
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Rutgers University
Department
Type
Schools of Arts and Sciences
DUNS #
038633251
City
New Brunswick
State
NJ
Country
United States
Zip Code
08901
Riley, L A; Jonakait, G M; Hart, R P (1993) Serotonin modulates the levels of mRNAS coding for thyrotropin-releasing hormone and preprotachykinin by different mechanisms in medullary raphe neurons. Brain Res Mol Brain Res 17:251-7
Walker, P D; Riley, L A; Hart, R P et al. (1991) Serotonin regulation of tachykinin biosynthesis in the rat neostriatum. Brain Res 546:33-9
Walker, P D; Green, T L; Jonakait, G M et al. (1991) A comparison of substance P peptide and preprotachykinin mRNA levels during development of rat medullary raphe and neostriatum. Int J Dev Neurosci 9:47-55
Riley, L A; Walker, P D; Hart, R P et al. (1991) Alterations of preprotachykinin (PPT) mRNA in medullary raphe occur following manipulation of serotonin. Ann N Y Acad Sci 632:455-6
Walker, P D; Ni, L; Riley, L A et al. (1991) Serotonin innervation affects SP biosynthesis in rat neostriatum. Ann N Y Acad Sci 632:485-7
Walker, P D; Riley, L A; Hart, R P et al. (1991) Serotonin regulation of neostriatal tachykinins following neonatal 6-hydroxydopamine lesions. Brain Res 557:31-6
Walker, P D; Schotland, S; Hart, R P et al. (1990) Tryptophan hydroxylase inhibition increases preprotachykinin mRNA in developing and adult medullary raphe nuclei. Brain Res Mol Brain Res 8:113-9