Fear conditioning-induced alterations of phospholipase C-beta 1a protein level and enzyme activity in rat hippocampal formation and medial frontal cortex

We investigated the effects of one-trial fear conditioning on phospholipase C-beta 1a catalytic activity and protein level in hippocampal formation an d medial frontal cortex of untreated control rats and rats prenatally expos ed to ethanol. One hour following fear conditioning of untreated control ra ts, phospholipase C-beta 1a protein level was increased in the hippocampal cytosolic fraction and decreased in the hippocampal membrane and cortical c ytosolic and cortical membrane fractions. Twenty-four hours after fear cond itioning, phospholipase C-beta 1a protein level was reduced in the hippocam pal cytosolic fraction and elevated in the cortical nuclear fraction; in ad dition, 24 h after conditioning, phospholipase C-beta 1a activity in the co rtical cytosolic fraction was increased. Rats that were exposed prenatally to ethanol displayed attenuated contextual fear conditioning, whereas condi tioning to the acoustic-conditioned stimulus was not different from control s. In behavioral control (unconditioned) rats, fetal ethanol exposure was a ssociated with reduced phospholipase C-beta1 a enzyme activity in the hippo campal nuclear, cortical cytosolic, and cortical membrane fractions and inc reased phospholipase C-beta 1a protein level in the hippocampal membrane an d cortical cytosolic fractions. In certain cases, prenatal ethanol exposure modified the relationship between fear conditioning and changes in phospho lipase C-beta 1a protein level and/or activity. The majority of these effec ts occurred 1h, rather than 24 h, after fear conditioning. Multivariate ana lysis of variance revealed interactions between fear conditioning, subcellu lar fraction, and prenatal ethanol exposure for measures of phospholipase C -beta 1a protein level in hippocampal formation and phospholipase C-beta 1a enzyme activity in medial frontal cortex. In the majority of cases, fear c onditioning-induced changes in hippocampal phospholipase C-beta 1a protein level were augmented in rats prenatally exposed to ethanol. In contrast, fe ar conditioning-induced changes in cortical phospholipase C-beta 1a activit y were, often, in opposite directions in prenatal ethanol-exposed compared to diet control rats. We speculate that alterations in subcellular phosphol ipase C-beta 1a catalytic activity and protein level contribute to contextu al fear conditioning and that learning deficits observed in rats exposed pr enatally to ethanol result, in part, from dysfunctions in phospholipase C-b eta 1a signal transduction. (C) 2001 Academic Press.