No abstract

The long-term impact of early stress on behavior and emotions is well documented in humans, and can be modeled in experimental animals. In mice, maternal separation during early postnatal development induces poor and disorganized maternal care, and results in behavioral deficits that persist through adulthood. Here, we examined the long-term effect of unpredictable maternal separation combined with maternal stress on behavior and its transmissibility. We report that unpredictable maternal separation from birth to postnatal day 14 in C57Bl/6J mice has mild behavioral effects in the animals when adult, but that its combination with maternal stress exacerbates this effect. Further, the behavioral deficits are transmitted to the following generation through females, an effect that is independent of maternal care and is not affected by cross-fostering. The combined manipulation does not alter basic components of the hypothalamic–pituitary–adrenal axis but decreases the expression of the corticotropin releasing factor receptor 2 (CRFR2) in several nuclei of the amygdala and the hypothalamus in the brain of maternal-separated females. These results suggest a non-genomic mode of transmission of the impact of early stress in mice.

Synaptic plasticity is a phenomenon contributing to changes in the efficacy of neuronal transmission. These changes are widely believed to be a major cellular basis for learning and memory. Protein phosphorylation is a key biochemical process involved in synaptic plasticity that operates through a tight balance between the action of protein kinases and protein phosphatases (PPs). Although the majority of research in this field has concentrated primarily on protein kinases, the significant role of PPs is becoming increasingly apparent. This review examines one such phosphatase, PP1, and highlights recent advances in the understanding of its intervention in synaptic and structural plasticity and the mechanisms of learning and memory.

SUMMARYTo investigate the pattern of expression of the three calmodulin (CaM) genes by in situ hybridization, gene-specific [ 35 S]-cRNA probes complementary to the multiple CaM mRNAs were hybridized in rat brain sections and subsequently detected by quantitative film or high-resolution nuclear emulsion autoradiography. A widespread and differential area-specific distribution of the CaM mRNAs was detected. The expression patterns corresponding to the three CaM genes differed most considerably in the olfactory bulb, the cerebral and cerebellar cortices, the diagonal band, the suprachiasmatic and medial habenular nuclei, and the hippocampus. Moreover, the significantly higher CaM I and CaM III mRNA copy numbers than that of CaM II in the molecular layers of certain brain areas revealed a differential dendritic targeting of these mRNAs. The results indicate a differential pattern of distribution of the multiple CaM mRNAs at two levels of cellular organization in the brain: (a) region-specific expression and (b) specific intracellular targeting. A precise and gene-specific regulation of synthesis and distribution of CaM mRNAs therefore exists under physiological conditions in the rat brain. (J Histochem Cytochem 47:583-600, 1999)