A fundamental question in neurobiology is how synaptic stimuli elicit long-term alterations in neuronal activity. Recent studies have demonstrated that neuronal stimulation can elicit rapid activation of several transcription factor genes. Accordingly, these factors, such as Zif268 and c-fos, are thought to play a key role in orchestrating alterations in gene expression underlying stimulus-induced neuronal plasticity. In previous studies, we have characterized extensively the regulation of zif268 in brain in several stimulation paradigms and found that it is markedly responsive to synaptic or pharmacologic stimuli. The goal of the proposed research outlined below is to move beyond these descriptive studies to define the mechanisms mediating neurotransmitter regulation to zif268. In particular, we plan to 1) use primary cortical cultures to study glutamate receptor regulation of zif268, and 2) examine the role of flanking DNA sequences in mediating neurotransmitter regulation of zif268. In the studies involving primary cortical cultures, I plan to integrate pharmacological and physiological approaches that I am largely familiar with. However, the studies examining regulatory DNA sequences will involve acquiring a wide range of advanced molecular biology techniques needed to study activity-dependent changes in gene expression in neuronal systems. To facilitate my professional growth in the area of molecular biology, I have arranged to consult on these projects with faculty members in the Departments of Neuroscience and Molecular Biology that have considerable expertise in this field.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research (K02)
Project #
1K02MH000926-01A1
Application #
3070294
Study Section
Research Scientist Development Review Committee (MHK)
Project Start
1992-05-01
Project End
1997-04-30
Budget Start
1992-05-01
Budget End
1993-04-30
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Taira, E; Finkenstadt, P M; Baraban, J M (1998) Identification of translin and trax as components of the GS1 strand-specific DNA binding complex enriched in brain. J Neurochem 71:471-7
Taira, E; Baraban, J M (1997) Identification of a strand-specific Egr response element binding complex enriched in rat brain. J Neurochem 68:2255-62
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Fosnaugh, J S; Bhat, R V; Yamagata, K et al. (1995) Activation of arc, a putative ""effector"" immediate early gene, by cocaine in rat brain. J Neurochem 64:2377-80
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Ratan, R R; Murphy, T H; Baraban, J M (1994) Macromolecular synthesis inhibitors prevent oxidative stress-induced apoptosis in embryonic cortical neurons by shunting cysteine from protein synthesis to glutathione. J Neurosci 14:4385-92
Blackstone, C; Murphy, T H; Moss, S J et al. (1994) Cyclic AMP and synaptic activity-dependent phosphorylation of AMPA-preferring glutamate receptors. J Neurosci 14:7585-93
Murphy, T H; Blatter, L A; Bhat, R V et al. (1994) Differential regulation of calcium/calmodulin-dependent protein kinase II and p42 MAP kinase activity by synaptic transmission. J Neurosci 14:1320-31

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