title: Fear conditioning-induced alterations of phospholipase C-beta1a protein level and enzyme activity in rat hippocampal formation and medial frontal cortex.
abstract: We investigated the effects of one-trial fear conditioning on phospholipase C-beta1a catalytic activity and protein level in hippocampal formation and medial frontal cortex of untreated control rats and rats prenatally exposed to ethanol. One hour following fear conditioning of untreated control rats, phospholipase C-beta1a protein level was increased in the hippocampal cytosolic fraction and decreased in the hippocampal membrane and cortical cytosolic and cortical membrane fractions. Twenty-four hours after fear conditioning, phospholipase C-beta1a protein level was reduced in the hippocampal cytosolic fraction and elevated in the cortical nuclear fraction; in addition, 24 h after conditioning, phospholipase C-beta1a activity in the cortical cytosolic fraction was increased. Rats that were exposed prenatally to ethanol displayed attenuated contextual fear conditioning, whereas conditioning to the acoustic-conditioned stimulus was not different from controls. In behavioral control (unconditioned) rats, fetal ethanol exposure was associated with reduced phospholipase C-beta1a enzyme activity in the hippocampal nuclear, cortical cytosolic, and cortical membrane fractions and increased phospholipase C-beta1a protein level in the hippocampal membrane and cortical cytosolic fractions. In certain cases, prenatal ethanol exposure modified the relationship between fear conditioning and changes in phospholipase C-beta1a protein level and/or activity. The majority of these effects occurred 1 h, rather than 24 h, after fear conditioning. Multivariate analysis of variance revealed interactions between fear conditioning, subcellular fraction, and prenatal ethanol exposure for measures of phospholipase C-beta1a protein level in hippocampal formation and phospholipase C-beta1a enzyme activity in medial frontal cortex. In the majority of cases, fear conditioning-induced changes in hippocampal phospholipase C-beta1a protein level were augmented in rats prenatally exposed to ethanol. In contrast, fear conditioning-induced changes in cortical phospholipase C-beta1a activity were, often, in opposite directions in prenatal ethanol-exposed compared to diet control rats. We speculate that alterations in subcellular phospholipase C-beta1a catalytic activity and protein level contribute to contextual fear conditioning and that learning deficits observed in rats exposed prenatally to ethanol result, in part, from dysfunctions in phospholipase C-beta1a signal transduction.
authors.affiliation: Department of Neurosciences, University of New Mexico, Albuquerque, New Mexico 87131-5223, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Weeber
authors.forename: D D
authors.initials: DD
authors.lastname: Savage
authors.forename: R J
authors.initials: RJ
authors.lastname: Sutherland
authors.forename: K K
authors.initials: KK
authors.lastname: Caldwell
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003213:Conditioning, Psychological; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D005239:Fear; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000196:embryology / Q000378:metabolism; D005625:Frontal Lobe / Q000201:enzymology*; D006624:Hippocampus / Q000201:enzymology*; D007527:Isoenzymes / Q000378:metabolism*; D054799:Phospholipase C beta; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D002492:Central Nervous System Depressants; D007527:Isoenzymes; D000431:Ethanol; D010738:Type C Phospholipases; D054799:Phospholipase C beta