Maternal behaviour in lactating rats stimulates c-fos in glutamate decarboxylase-synthesizing neurons of the medial preoptic area, ventral bed nucleus of the stria terminalis, and ventrocaudal periaqueductal gray

Abstract

Increased activity of the immediate-early gene c-fos can be observed in many areas of the lactating rat brain after dams physically interact with pups and display maternal behaviour. These sites include the medial preoptic area, ventral bed nucleus of the stria terminalis, and the ventrolateral caudal periaqueductal gray, each of which is critical for the normal performance of particular maternal behaviours. The phenotype of cells in these areas that show increased c-fos activity after maternal behaviour, however, is unknown. Via double-label immunocytochemistry, we determined if the population of cells in these sites that express c-fos after maternal behaviour in lactating rats overlaps with the population that expresses the 67,000 mol. wt isoform of glutamate decarboxlyase, the synthesizing enzyme for the inhibitory neurotransmitter GABA. Lactating rats were separated from pups beginning on day 5 postpartum, and 48h later half were allowed to interact with a litter of pups for 60min whereas the other half were not. Dams re-exposed to pups were highly maternal, retrieving and licking them as well as displaying prolonged nursing behaviour that included milk letdown. Both groups of dams had a similar number of 67,000 mol. wt glutamate decarboxylase-immunoreactive cells in each site, although the number of 67,000 mol. wt glutamate decarboxylase-immunoreactive cells per microscopic field was significantly greater in the caudal ventrolateral periaqueductal gray than in the ventral bed nucleus of the stria terminalis, which in turn was greater than the medial preoptic area. In pup-stimulated dams, two to fourfold more Fos-immunoreactive cells were found in these three sites compared with non-stimulated controls. Labeling for Fos immunoreactivity and 67,000 mol. wt glutamate decarboxylase immunoreactivity was heterogeneous within each site. In the medial preoptic area, more Fos-immunoreactive and 67,000 mol. wt glutamate decarboxylase-immunoreactive cells (either single or dual-labeled) were found dorsally than ventrally. In the ventral bed nucleus of the stria terminalis, more Fos-immunoreactive and 67,000 mol. wt glutamate decarboxylase-immunoreactive cells were found medially than laterally. Within the caudal ventrolateral periaqueductal gray, 67,000 mol. wt glutamate decarboxylase-immunoreactive labeling was greatest ventromedially, while high numbers of Fos-immunoreactive nuclei were found both ventromedially and ventrolaterally. In pup-stimulated dams, more than half (53% in the medial preoptic area, 59% in the ventral bed nucleus of the stria terminalis, and 61% in the caudal ventrolateral periaqueductal gray) of the total population of Fos-immunoreactive cells also expressed 67,000 mol. wt glutamate decarboxylase. These results suggest that many of the neurons in these sites that show elevated c-fos activity after maternal behaviour are either local inhibitory interneurons or provide inhibitory input to other neural sites. These inhibitory mechanisms may be critical for the display of postpartum nurturance, possibly facilitating maternal behaviour by removing tonic inhibition on sites necessary for maternal responding or by restricting activity in neural sites that inhibit it.