The goal is to identify and characterize biochemical parameters that distinguish neuronal cell types within the hippocampal formation. The hippocampus is chosen as a model for cellular and regional specific gene expression because of its relatively simple anatomical organization, consisting of only several major neuronal cell types and because of its well characterized developmental, electrophysiological and neurotransmitter properties. We will examine the anatomical distribution of the expression of specific mRNA transcripts both within the defined subnuclear organization of the hippocampus and with respect to their potential expression in neurons of other regions of the brain. The developmental program of expression will be investigated in both normal and mutant strains of mice to distinguish those transcripts accumulated during cell migration from those expressed only after synaptogenesis. The primary sequence of the encoded protein will be determined and evaluated in terms of potential signal peptides, glycosylation and proteolytic cleavage. These post-translational modifications, together with the neuroanatomical distribution of their expression, should provide important clues as to the nature of the specific proteins. It is believed that these studies will contribute to an understanding of the biochemical basis of hippocampal function. Experimentally induced lesion and clinical studies have associated the hippocampal formation with such complex behavioral phenomena as acquisition and processing of short term memory and propagation of epileptic seizures. For example, a potential animal model for certain forms of epilepsy in humans, the mutant mouse strain """"""""tottering"""""""", will be examined for alterations in patterns of gene expression which may result from the primary defect of hyperinnervation by noradrenergic axons of the locus coeruleus to the hippocampal formation. These studies, therefore, could result in future examination of the role of specific gene products during experimentally induced seizure activity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS023038-01A1
Application #
3406027
Study Section
Neurology C Study Section (NEUC)
Project Start
1986-08-01
Project End
1989-07-31
Budget Start
1986-08-01
Budget End
1987-07-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
San Diego
State
CA
Country
United States
Zip Code
92037
Hess, D T; Slater, T M; Wilson, M C et al. (1992) The 25 kDa synaptosomal-associated protein SNAP-25 is the major methionine-rich polypeptide in rapid axonal transport and a major substrate for palmitoylation in adult CNS. J Neurosci 12:4634-41
Hess, E J; Jinnah, H A; Kozak, C A et al. (1992) Spontaneous locomotor hyperactivity in a mouse mutant with a deletion including the Snap gene on chromosome 2. J Neurosci 12:2865-74
Catsicas, S; Catsicas, M; Keyser, K T et al. (1992) Differential expression of the presynaptic protein SNAP-25 in mammalian retina. J Neurosci Res 33:1-9
Sanna, P P; Bloom, F E; Wilson, M C (1991) Dibutyryl-cAMP induces SNAP-25 translocation into the neurites in PC12. Brain Res Dev Brain Res 59:104-8
Catsicas, S; Larhammar, D; Blomqvist, A et al. (1991) Expression of a conserved cell-type-specific protein in nerve terminals coincides with synaptogenesis. Proc Natl Acad Sci U S A 88:785-9
Hess, E J; Wilson, M C (1991) Tottering and leaner mutations perturb transient developmental expression of tyrosine hydroxylase in embryologically distinct Purkinje cells. Neuron 6:123-32
Oyler, G A; Polli, J W; Wilson, M C et al. (1991) Developmental expression of the 25-kDa synaptosomal-associated protein (SNAP-25) in rat brain. Proc Natl Acad Sci U S A 88:5247-51
Lipkin, W I; Wilson, M C; Oldstone, M B (1990) Molecular insights into infections of the central nervous system. Res Publ Assoc Res Nerv Ment Dis 68:15-22
Geddes, J W; Hess, E J; Hart, R A et al. (1990) Lesions of hippocampal circuitry define synaptosomal-associated protein-25 (SNAP-25) as a novel presynaptic marker. Neuroscience 38:515-25
Trimble, W S; Gray, T S; Elferink, L A et al. (1990) Distinct patterns of expression of two VAMP genes within the rat brain. J Neurosci 10:1380-7

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