Previous studies from our laboratory have indicated that genetic differences in spatial learning performance can be revealed using the Morris water task. C57BL/6 mice performed relatively well while DBA/2 mice perform poorly on the task. These strains and many recombinant inbred strains generated from a C57 X DBA/2 cross show variation in spatial learning performance and this variation is significantly correlated to hippocampal protein kinase C activity. Protein kinase C (PKC) is activated via generation of diacylglycerol during phosphatidyl inositol turnover, an important second messenger in brain. Because of the central role of PKC in the brain, it provides an important substrate for further investigation using a genetic approach. We purpose to examine the role of hippocampal PKC in determining genetic differences in learning performance from several perspectives. The nature of the learning deficit in DBA mice will be examined further using behavioral approaches. The question of whether protein kinase C activity changes as a function of training will also be investigated. Biochemical studies will be designed to elucidate the nature of the strain differences in hippocampal PKC activity by investigating the isozymic patterns in C57 and DBA mice. Molecular genetic studies will examine the DNA sequence of the major PKC genes from C57 and DBA mice; the expression of these genes in brain and potential effects of training on gene expression; and the regional localization of this expression will be examined by in situ hybridizations. The results of the proposed studies should allow a more complete assessment of the nature of spatial learning performance deficits, and provide information as to approaches for the future correction of such deficits. Furthermore, the role of hippocampal PKC in learning and memory processes should be delineated.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Molecular, Cellular, and Developmental Neurobiology Review Committee (MCDN)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Colorado at Boulder
Other Domestic Higher Education
United States
Zip Code
Cohen, Howard; Amerine-Dickens, Mila; Smith, Tristram (2006) Early intensive behavioral treatment: replication of the UCLA model in a community setting. J Dev Behav Pediatr 27:S145-55
Paylor, R; Johnson, R S; Papaioannou, V et al. (1994) Behavioral assessment of c-fos mutant mice. Brain Res 651:275-82
Paylor, R; Tracy, R; Wehner, J et al. (1994) DBA/2 and C57BL/6 mice differ in contextual fear but not auditory fear conditioning. Behav Neurosci 108:810-7
Miller, S; Wehner, J M (1994) Cholesterol treatment facilitates spatial learning performance in DBA/2Ibg mice. Pharmacol Biochem Behav 49:257-61
Abeliovich, A; Paylor, R; Chen, C et al. (1993) PKC gamma mutant mice exhibit mild deficits in spatial and contextual learning. Cell 75:1263-71
Fordyce, D E; Wehner, J M (1993) Effects of aging on spatial learning and hippocampal protein kinase C in mice. Neurobiol Aging 14:309-17
Fordyce, D E; Wehner, J M (1993) Physical activity enhances spatial learning performance with an associated alteration in hippocampal protein kinase C activity in C57BL/6 and DBA/2 mice. Brain Res 619:111-9