A variety of behavioral, metabolic, structural, and neuroendocrine alterations occur during the transition from a virgin to a lactating state 
. These physiological adaptations during lactation are believed to be critically important for the survival and development of the offspring. For example, in rodents, within hours of parturition, the mother retrieves the scattered pups, gathers them together in the nest, and adopts a nursing posture over the pups to permit suckling 
. Adaptive changes in several neuroendocrine systems during lactation are also evident. For example, the release of both adrenocorticotropic hormone and corticosterone in response to various stressors is markedly suppressed 
. A striking change in metabolic aspect during lactation is the negative energy balance resulting from the increased energy demand and decreased adaptive thermogenesis 
. This energy-saving mechanism facilitates the availability of energy for milk production.
The mammalian septum is a heterogeneous forebrain structure that is divided into two main subdivisions, the medial septum (MS) and the lateral septum (LS), and has been linked to various aspects of maternal care, including offspring protection and pup retrieval 
. Neuroanatomically, MS is densely interconnected with the hippocampus while LS has extensive reciprocal connections with numerous brain regions known to regulate affect and motivation, such as hypothalamus, amygdala, bed nucleus of the stria terminalis, periaqueductal gray, ventral tegmental area, and raphe nuclei 
. Neurochemically, a high number of neurons in LS contain GABA and in subregions of LS, neurons also express other neurotransmitters, such as neurotensin, enkephalin, galanin, and somatostatin 
. Neurons within MS are predominantly GABAergic and/or cholinergic 
. LS has long been considered to play a critical role in regulating multiple affective, behavioral and cognitive processes, such as fear, anxiety, depression, aggression, maternal behavior, and social recognition 
. MS functions mainly as a region that modulates processes related to attention and memory 
Alterations in neuronal activity and gene expression in several brain regions during the postpartum period have been reported. For example, during lactation, neuronal activity of neuropeptide Y (NPY) and agouti-related protein are increased in the arcuate nucleus of hypothalamus (Arc), a site known to be a core feeding center, whereas proopiomelanocortin is reduced 
. These changes in neuropeptide activity have been proposed to be important in integrating Arc-mediated food intake and energy balance. Expression changes of some genes in forebrain structures during lactation have been demonstrated to be involved in the control of maternal/parental and/or reproductive behaviors 
. However, possible alterations in gene expression in the septum that may contribute to the septum-mediated adaptations during lactation remain largely unexplored. In this study, we employed microarray analysis to identify genes in the septum with altered expression during the postpartum period.
As part of this study, we were also interested in how identified gene expression differences may have occurred. Producing the maternal brain is a complex process and is associated with various contributing factors including hormonal changes and sensory input from different events, such as the mating, parturition, nursing, and additional interactions with offspring 
. There are likely large numbers of transcription factors that contribute to the gene expression changes but which have not to date been evaluated. Newer data mining tools, such as gene set enrichment analysis (GSEA), provide a unique approach to gain insight into how altered gene expression occurs 
. The databases include for each gene information on all known binding sites in that region, including those for a wide range of transcription factors and microRNAs (miRNAs), that may be involved in gene expression. MiRNAs are of interest because they have been implicated in peripheral alterations, such as placenta and mammary gland development 
in the maternal female, but to date no roles for miRNAs have been examined for the maternal brain. In this study, we used GSEA to gain insights into how large scale changes may have been occurring during pregnancy and early lactation with a subset of transcriptional regulators.