Hidden Markov Model Analysis of Maternal Behavior Patterns in Inbred and Reciprocal Hybrid Mice

Individual variation in maternal care in mammals shows a significant heritable component, with the maternal behavior of daughters resembling that of their mothers. In laboratory mice, genetically distinct inbred strains show stable differences in maternal care during the first postnatal week. Moreover, cross fostering and reciprocal breeding studies demonstrate that differences in maternal care between inbred strains persist in the absence of genetic differences, demonstrating a non-genetic or epigenetic contribution to maternal behavior. In this study we applied a mathematical tool, called hidden Markov model (HMM), to analyze the behavior of female mice in the presence of their young. The frequency of several maternal behaviors in mice has been previously described, including nursing/grooming pups and tending to the nest. However, the ordering, clustering, and transitions between these behaviors have not been systematically described and thus a global description of maternal behavior is lacking. Here we used HMM to describe maternal behavior patterns in two genetically distinct mouse strains, C57BL/6 and BALB/c, and their genetically identical reciprocal hybrid female offspring. HMM analysis is a powerful tool to identify patterns of events that cluster in time and to determine transitions between these clusters, or hidden states. For the HMM analysis we defined seven states: arched-backed nursing, blanket nursing, licking/grooming pups, grooming, activity, eating, and sleeping. By quantifying the frequency, duration, composition, and transition probabilities of these states we were able to describe the pattern of maternal behavior in mouse and identify aspects of these patterns that are under genetic and nongenetic inheritance. Differences in these patterns observed in the experimental groups (inbred and hybrid females) were detected only after the application of HMM analysis whereas classical statistical methods and analyses were not able to highlight them

Differences in Mouse Maternal Care Behavior – Is There a Genetic Impact of the Glucocorticoid Receptor?

Depressive episodes are frequently preceded by stressful life events. Evidence from genetic association studies suggests a role for the glucocorticoid receptor (GR), an essential element in the regulation of stress responses, in the pathophysiology of the disorder. Since the stress response system is affected by pregnancy and postpartum-associated changes, it has also been implicated in the pathophysiology of postpartum depression. Using a 2×2 factorial design, we investigated whether a heterozygous deletion of GR would influence maternal care behavior in C57BL/6 and Balb/c mice, two inbred strains known to display qualitative differences in this behavior. Behavioral observation was carried out between postnatal days 1 and 7, followed by a pup retrieval test on postnatal days 7 or 8. While previously noted inter-strain differences were confirmed for different manifestations of caring behavior, self-maintenance and neglecting behaviors as well as the pup retrieval test, no strain-independent effect of the GR mutation was noted. However, an interaction between GR genotype and licking/grooming behavior was observed: it was down-regulated in heterozygous C57BL/6 mice to the level recorded for Balb/c mice. Home cage observation poses minimal disturbance of the dam and her litter as compared to more invasive assessments of dams' emotional behavior. This might be a reason for the absence of any overall effects of the GR mutation, particularly since GR heterozygous animals display a depressive-like phenotype under stressful conditions only. Still, the subtle effect we observed may point towards a role of GR in postpartum affective disorders

Killian-Jamieson diverticulum: A rare cause of dysphagia

Pharyngoesophageal diverticula are a rare anatomical abnormality and are classified in 3 types based on the area of their protrusion: Zenker diverticulum is the most common, followed by Killian-Jamieson diverticulum and the rarest, Laimer diverticulum. We report a case of a 68-year-old man who presented to our clinic with a 3-year history of moderate anemia uncovered after routine blood tests, progressive dysphagia for solids and food bolus impactions resolved spontaneously. Upper endoscopy revealed a wide-mouthed diverticulum, measuring 2-3 cm, with normal mucosa and food residue inside, just below the upper esophageal sphincter, on the left side of the esophageal wall and also hiatal hernia with diffuse mucosal bleeding. Subsequent barium swallow study showed as well a 25 mm left-sided outpouching arising from the anterolateral wall of the proximal cervical esophagus, consistent with a Killian-Jamieson diverticulum. Killian-Jamieson diverticulum is a rare condition with a highly variable clinical presentation, most often reported symptoms being dysphagia, regurgitation and globus sensation