GENETIC AND ACTIVITY-DEPENDENT REGULATION OF ZIF268 EXPRESSION - ASSOCIATION WITH SPATIAL-LEARNING

We have reported that C57BL/6 and DBA/2 mice differ in spatial learnin g performance and associated hippocampal protein kinase C (PKC) activi ty (Upchurch and Wehner, 1989, Behav Neurosci 103:1251-1258; Wehner et al., 1990, Brain Res 523:181-187) and that physical activity enhances spatial learning with related alterations in protein kinase C (PKC) ( Fordyce and Wehner, 1993b, Brain Res 619:111-119). To assess whether p hysical activity induces alterations in gene expression that may under lie these changes in PKC and learning performance, we examined the eff ect of physical activity on expression of zif268, a transcription regu latory factor linked to stimulus-induced neuronal plasticity. C57 and DBA mice, 3 months of age, were subjected to acute (one bout) or chron ic (8 weeks) physical activity. The mice were then tested on the Morri s water maze task for 6 days with subsequent analysis of PKC activity and zif268 mRNA expression. Control DBA mice, which have poor hippocam pal-specific learning performance compared to C57 mice (Wehner et al., 1990, Brain Res 523:181-187; Fordyce and Wehner, 1993b, Brain Res 619 :111-119; Paylor et al., 1993, Psychobiology 27:11-26), displayed lowe r basal levels of zif268 mRNA (P <.05). As observed previously, chroni c physical activity produced an enhancement in spatial learning perfor mance accompanied by alterations in hippocampal PKC activity in both s trains of mice (P < .05). In addition, the present investigation demon strated that acute physical activity increased mRNA levels of zif268 i n hippocampal regions CA1, CA3 and overlying cortex (P <.005) of both C57 and DBA mice. Chronic physical activity suppressed the basal expre ssion of zif268 in C57 mice in CA1 and overlying cortex below control levels. These findings suggest that genetic and activity-dependent reg ulation of zif268 may influence learning performance. (C) 1994 Wiley-L iss, Inc.