Variations in maternal care alter GABA(A) receptor subunit expression in brain regions associated with fear.
Maternal care influences the development of stress reactivity in the offspring. These effects are accompanied by changes in corticotropin-releasing factor (CRF) expression in brain regions that regulate responses to stress. However, such effects appear secondary to those involving systems that normally serve to inhibit CRF expression and release. Thus, maternal care over the first week of life alters GABA(A) (gamma-aminobutyric acid)(A) receptor mRNA subunit expression. The adult offspring of mothers that exhibit increased levels of pup licking/grooming and arched back-nursing (high LG-ABN mothers) show increased alpha1 mRNA levels in the medial prefrontal cortex, the hippocampus as well as the basolateral and central regions, of the amygdala and increased gamma2 mRNA in the amygdala. Western blot analyses confirm these effects at the level of protein. In contrast, the offspring of low LG-ABN mothers showed increased levels of alpha3 and alpha4 subunit mRNAs. The results of an adoption study showed that the biological offspring of low LG-ABN mothers fostered shortly after birth to high LG-ABN dams showed the increased levels of both alpha1 and gamma2 mRNA expression in the amygdala in comparison to peers fostered to other low LG-ABN mothers (the reverse was true for the biological offspring of high LG-ABN mothers). These findings are consistent with earlier reports of the effects of maternal care on GABA(A)/benzodiazepine receptor binding and suggest that maternal care can permanently alter the subunit composition of the GABA(A) receptor complex in brain regions that regulate responses to stress.
Caldji
Christian
C
Developmental Neuroendocrinology laboratory, Douglas Hospital Research Centre, McGill University, Montréal, Canada H4H 1R3.
Diorio
Josie
J
Meaney
Michael J
MJ
D000818:Animals; D001921:Brain / Q000378:metabolism*; D005239:Fear / Q000502:physiology* / Q000523:psychology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D008425:Maternal Behavior / Q000502:physiology* / Q000523:psychology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D020318:Rats, Long-Evans; D011963:Receptors, GABA-A / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D011963:Receptors, GABA-A