Activation of a novel p70 S6 kinase 1-dependent intracellular cascade in the basolateral nucleus of the amygdala is required for the acquisition of extinction memory.

Repeated presentations of a previously conditioned stimulus lead to a new form of learning known as extinction, which temporarily alters the response to the original stimulus. Previous studies have shown that the consolidation of extinction memory requires de novo protein synthesis. However, the role of specific nodes of translational control in extinction is unknown. Using auditory threat conditioning in mice, we investigated the role of mechanistic target of rapamycin complex 1 (mTORC1) and its effector p70 S6 kinase 1 (S6K1) in the extinction of auditory threat conditioning. We found that rapamycin attenuated the consolidation of extinction memory. In contrast, genetic deletion and pharmacological inhibition of S6K1, a downstream effector of mTORC1, blocked within-session extinction, indicating a role for S6K1 independent of protein synthesis. Indeed, the activation of S6K1 during extinction required extracellular signal-regulated kinase (ERK) activation in the basolateral nucleus of the amygdala (BLA) and was necessary for increased phosphorylation of the GluA1 (Thr840) subunit of the AMPA receptor following extinction training. Mice exposed to brief uncontrollable stress showed impaired within-session extinction as well as a downregulation of ERK and S6K1 signaling in the amygdala. Finally, using fiber photometry we were able to record calcium signals in vivo, and we found that inhibition of S6K1 reduces extinction-induced changes in neuronal activity of the BLA. These results implicate a novel ERK-S6K1-GluA1 signaling cascade critically involved in extinction.

Lactation, nutrition and fertility and the secretion of prolactin and gonadotrophins in Mopan Mayan women.

The effect of lactation on menstrual cycles, ovulation and conception was studied in a group of non-contracepting Amerindian Mopan Mayan women. Anthropological observations of relevant events were made over a 21-month period. Blood samples were assayed to determine the plasma concentrations of prolactin, luteinising hormone, follicle stimulating hormone, human chorionic gonadotrophin, placental lactogen, oestrogen, progesterone and cortisol. The data show that: frequent and prolonged breast-feeding was associated with a marked increase in plasma prolactin concentrations to levels similar to those in lactating Gaing but higher than those in lactating Scottish women; ovulatory menstrual cycles and pregnancy occurred during frequent lactation; in lactating menstruating women there was an inverse correlation between fat weight and months post-partum. These data suggest that other factors as well as suckling account for the effects of lactation on fecundity.

PIP: Lactation, ovulation and conception were observed as part of an anthropological study of Amerindian Mopan Mayan women from the village of San Jose Hawaii in western Belize from March 1985-January 1987. Single blood samples from each subject were immunoassayed for prolactin, LH, FSH, hCG, placental lactogen, estrogen, progesterone and cortisol. Anthropomorphic data analyzed were body mass index (BMI), fat/weight percentage, total body water and lean body weight. 117 women had at least 1 child during the study; 91 were lactating; 51 reported no menstrual cycles. 50 submitted to blood testing. Almost all infants were breast fed for 18 months or longer, up to 3 years, typically at least 6 times per day and 3 times per night. Women averaged 9 live births and 8 surviving children, with a mean birth interval of 28 months. 25 of the 29 women known to be pregnant conceived while lactating. 16 lactating women were pregnant. Their culture requires them to have 3 menses before conception to nourish the fetus, yet forbids speaking about menstrual blood: women fabricated menstrual dates, but in confidence 51 of 81 stated that they did not menstruate before the last conception. Most often menses began 12 months postpartum. Lactating women had heightened prolactin levels even if supplementing their children's diet. Thus frequent lactation delayed onset of menses, but supplementation had no effect. Most of the women were within the normal range of BMI, but 13% were below normal. In lactating menstruating women there was a significant negative correlation between fat weight and postpartum month. The data suggest that the interval to conception or menstruation was inversely correlated with fat weight. Here suckling frequency rather than prolactin levels seems to postpone fertility. In this society, with 10-12 births and 9-10 children in the completed family, the largest in the world, prolonged frequent lactation has little effect on fertility. Instead, birth trauma, maternal mortality, fetal and infant mortality, and perhaps nutrition, have more effect on completed family size.

Nutrition, lactation and fertility in two Mexican rural communities.

Policies are currently being pursued in Third World countries which promote lactation as both a fertility control measure and a means of improving child health and decreasing infant mortality rates. However, the relationship between nutrition, lactation and fertility in the human is a complex one in which social and psychological factors are involved as well as physiological and biochemical mechanisms. Little is known about the effects of these social and psychological variables on the biological processes. Observations made in the course of the anthropological fieldwork study reported in this paper raise questions regarding the assumption of the universal applicability of lactation policies in third world countries. Findings from this study are supported by the anthropological literature which indicates that breast feeding behaviour is culturally patterned and that there is a wide variation in such behaviour. The variations in environmental resources as well as in the ideological notions of nutrition which pattern the behaviour governing the exploitation of such resources as well as feeding behaviour is seen as advantageous in that they provide a 'natural laboratory' situation for examining the conflicting hypotheses concerning the relationship between nutrition, lactation and fertility.