Abstract
Coordinated gene expression changes across the CNS are required to produce the mammalian maternal phenotype. Lateral septum (LS) is a brain region critically involved with aspects of maternal care, and we recently examined gene expression of whole septum (LS and medial septum) in selectively bred maternal mice. Here, we expand on the prior study by 1) conducting microarray analysis solely on LS in virgin and postpartum mice, 2) using outbred mice, and 3) evaluating the role of sensory input on gene expression changes. Large scale changes in genes related to neuronal signaling were identified, including four GABAA receptor subunits. Subunits α4 and δ were downregulated in maternal LS, likely reflecting a reduction in the extrasynaptic, neurosteroid-sensitive α4/δ containing receptor subtype. Conversely, subunits ε and θ were increased in maternal LS. Fifteen K+ channel related genes showed altered expression, as did dopamine receptors Drd1a and Drd2 (both downregulated), hypocretin receptor 1 (Hcrtr1), kappa opioid receptor 1 (Oprk1), and transient receptor potential channel 4 (Trpc4). Expression of a large number of genes linked to developmental processes or cell differentiation were also altered in postpartum LS, including chemokine (C-X-C) motif ligand 12 (Cxcl12), fatty acid binding protein 7 (Fabp7), plasma membrane proteolipid (Pllp), and suppressor of cytokine signaling 2 (Socs2). Additional genes that are linked to anxiety, such as glutathione reductase (Gsr), exhibited altered expression. Pathway analysis also identified changes in genes related to cyclic nucleotide metabolism, chromatin structure, and the Ras gene family. The sensory presence of pups was found to contribute to the altered expression of a subset of genes across all categories. This study suggests that both large changes in neuronal signaling and the possible terminal differentiation of neuronal and/or glial cells play important roles in producing the maternal state.
Highlights
The establishment of the maternal phenotype requires a coordinated suite of changes in numerous biological pathways, from endocrine signaling and metabolic activity to nervous system properties and adaptive behaviors [1,2,3]
Genes of interest reported in the microarray results include GABAA receptor subunits; a1 (Gabra1) (FDR-adjusted p = 0.32, fold change 1.06), Gabra4 (FDR-adjusted p = 0.21, fold change 0.88), Gabrd (FDR-adjusted p = 0.11, fold change 0.75), Gabre (FDRadjusted p = 0.12, fold change 1.38), Gabrq (FDR-adjusted p = 0.42, fold change 1.26), Cxcl12 (FDR-adjusted p = 0.25, fold change 1.14), fatty acid binding protein 7 (Fabp7) (FDR-adjusted p = 0.20, fold change = 0.71), Gsr (FDR-adjusted p = 0.37, fold change 0.92), plasma membrane proteolipid (Pllp) (FDRadjusted p = 0.25, fold change 0.89), and suppressor of cytokine signaling 2 (Socs2) (FDR-adjusted p = 0.30, fold change 1.27)
The results reveal numerous changes in genes of interest that may be of particular importance as markers of the maternal phenotype, including differential regulation of GABAA receptor subtypes
Summary
The establishment of the maternal phenotype requires a coordinated suite of changes in numerous biological pathways, from endocrine signaling and metabolic activity to nervous system properties and adaptive behaviors [1,2,3]. Maternal behavior in many mammals is critical for the survival of offspring. In mice, this includes behaviors such as nest building, nursing, and protection of offspring [4]. Additional emotional pathways altered in the postpartum state include fear, stress, and anxiety. The transition from a virgin to lactating state provides a unique and powerful opportunity to examine the fundamental neurophysiology of a range of emotional traits because the observed changes are naturally occurring
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