The long term objectives of this application will be to further the understanding of the molecular basis of learning and memory and to apply this knowledge to studies of diseases, such as Alzheimer's Disease. It is widely accepted that the acquisition of long-term memory is a process which depends upon protein synthesis. Hence, it has been postulated that this process is linked to the expression of one or more genes which may be involved in long-term adaptive modifications within the cell. Studies of invertebrate behavior have disclosed that simple forms of learning are characterized by molecular and ionic events with result in changes in synaptic function. Such changes also occur with long-term potentiation (LTP) which has been proposed as a model of neural plasticity and long- term memory processing in the mammalian nervous system. The acquisition of long-term memory bears a striking resemblance to processes which occur during cell growth and differentiation. Therefore, this application will focus on defining the molecular events underlying LTP by examining the level of expression of a proto-oncogene, c-fos. Protooncogenes, such as c-fos, are thought to play a regulatory role in cell growth and differentiation. Hence, it is possible that the heightened neuronal activity associated with LTP is related to c-for induction. We will use c-fos cDNA as a probe and perform Northern blot and in situ hybridization studies to evaluate the level of expression and localize the signal of c- fos message in the rat and rabbit hippocampus during LTP. Immunohistochemical techniques will be conducted to localize Fos protein. In this way, a gene or genes which are important in memory mechanisms and an anatomic substrate of LTP may be identified. Changes in levels of c- fos expression with age will also be studied. It is hoped that these studies will contribute to further understanding of the molecular basis of normal and abnormal cognitive function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08NS001337-03
Application #
3084288
Study Section
Neurological Disorders Program Project Review B Committee (NSPB)
Project Start
1989-06-01
Project End
1994-05-31
Budget Start
1991-06-01
Budget End
1992-05-31
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Southern California
Department
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Tan, Z; Levid, J; Schreiber, S S (2001) Increased expression of Fas (CD95/APO-1) in adult rat brain after kainate-induced seizures. Neuroreport 12:1979-82
Tan, Z; Qu, W; Tu, W et al. (2000) p53 accumulation due to down-regulation of ubiquitin: relevance for neuronal apoptosis. Cell Death Differ 7:675-81
Sakhi, S; Bruce, A; Sun, N et al. (1994) p53 induction is associated with neuronal damage in the central nervous system. Proc Natl Acad Sci U S A 91:7525-9
Najm, I; Schreiber, S S; Baudry, M (1993) Transcriptional activation of ornithine decarboxylase in adult and neonatal hippocampal slices. Brain Res Dev Brain Res 74:193-7
Schreiber, S S; Tocco, G; Najm, I et al. (1993) Seizure activity causes a rapid increase in sulfated glycoprotein-2 messenger RNA in the adult but not the neonatal rat brain. Neurosci Lett 153:17-20
Schreiber, S S; Najm, I; Tocco, G et al. (1993) Co-expression of HSP72 and c-fos in rat brain following kainic acid treatment. Neuroreport 5:269-72
Wei, W; Schreiber, S S; Baudry, M et al. (1993) Localization of the cellular expression pattern of cdc25NEF and ras in the juvenile rat brain. Brain Res Mol Brain Res 19:339-44
Schreiber, S S; Tocco, G; Najm, I et al. (1993) Cycloheximide prevents kainate-induced neuronal death and c-fos expression in adult rat brain. J Mol Neurosci 4:149-59
Schreiber, S S; Tocco, G; Najm, I et al. (1992) Absence of c-fos induction in neonatal rat brain after seizures. Neurosci Lett 136:31-5
Schreiber, S S; Maren, S; Tocco, G et al. (1991) A negative correlation between the induction of long-term potentiation and activation of immediate early genes. Brain Res Mol Brain Res 11:89-91

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