Mouse helpers ensure maternal-infant survival

Abstract

Parental care is required to ensure the health and survival of offspring. Caretaking in mammals is challenging as infants are largely helpless and require near-continual oversight over prolonged periods. Mouse pups in particular cannot thermoregulate, and will succumb to hypothermia unless kept warm by an adult caretaker or an insulating nest. Parents must balance caretaking behaviors with other activities important for survival such as regulating their own temperature and foraging for food or water, which necessarily involve periods of pup neglect. To understand in high detail the consequential decision-making involved in care of infant pups, we built a new system for long-term 24/7 continuous monitoring of mouse homecage behaviors, including thermal imaging, video recording from above, side and directly under the nest, with environmental controls to standardize housing conditions across animals. We monitored single dams and their offspring, before, during and after parturition, from initial mating over four consecutive litters. We found that about half of the animals had high litter survival rates (high-pup-survival dams) but the other half had little to no pups survive (low-pup-survival dams). The relative amount of litter survival did not change or improve across litters in absence of intervention: Low-pup-survival dams continued to neglect pups and nest-building across litters, losing nearly all offspring within a day after birth. We could predict which animals would become low-pup-survival dams by inspecting the nests they built a few days before parturition. Low-pup-survival dams minimally engaged with nest building, and after birth, generally avoided pups and the nest. Nest quality deteriorated due to movement of the dam in and out of the nest, exacerbating temperature loss and mortality of the litter. In contrast, high-pup-survival dams spent a considerable amount of time rebuilding and adjusting the nest over the first postnatal day and beyond. Remarkably, if we co-housed low-pup-survival dams with a high-pup-survival dam and her litter, when the low-pup-survival dam was bred again and singly-housed, litter survival rates thereafter were consistently much higher along with increased attention toward pups and nest. Thus, even under well-controlled and ideal lab housing conditions, mouse maternal care can be remarkably variable, with continued nest rebuilding as the most important factor in ensuring high litter survival rates. Furthermore, despite some animals perseverating in maternal neglect and losing their pups, caretaking and nest-building can improve after interactions with experienced and successful parents.

The lateral habenula is required for maternal behavior in the mouse dam

“…While standard maternal behavior tests (MBTs) were planned to begin on lactation day 2 (LD2), half of all dams' (8/16) litters had died by then. Instead, naturalistic MBTs (Carcea et al, 2021;Dvorkin and Shea, 2022;Schuster et al, 2023) were scored from footage obtained on LD1 in which all dams showed activity. Naturalistic MBT analysis showed that 7/8 kainic acid-treated dams failed to engage in any maternal behavior, resulting in the death of 100% of their litters by LD2.…”

“…Notably, the only kainic acid-treated dam that performed maternal behavior at control levels (mouse X306) was later shown to have the same number of total surviving neurons as those from the saline-treated group (Figure 2A, B, Extended Figure 7-2). The only saline-treated dam that neglected her pups (Figure 1C-E) may have reflected the known baseline rate of neglect in mouse dams (Schuster et al, 2023), as her brain could not be assessed for possible accidental injection damage, since the brain tissue from 5 animals (2 saline-treated and 3 kainic acidtreated), including hers, was damaged during COVID-19 lab shut downs and so the subsequent histology was uninterpretable.…”

“…As such, primiparous mouse dams do not need to learn to build nests. But since highly-motivated nest building and high nest scores in pregnant female mice predict engagement in other maternal behaviors as well as pup survival (Schuster et al, 2023), nest building motivation is an important maternal behavior variable. Across all days, control group dams spent significantly more time engaged in nest building than DREADD group dams (Figure 4A, Extended Figure 3-1).…”

Automated behavioral scoring: Do we even need humans?

“…A recent preprint by Schuster and colleagues suggests a way forward using continuous home-cage recording and DeepLabCut to gauge maternal presence in the nest. 13 Similarly, Winters and colleagues recently reported on the automation of the pup retrieval test. 14 My lab has also recently begun using a similar, albeit a simplistic, example of parental behavior automation.…”

“…One of the strengths of automated behavior scoring is in identifying postures, for which automated approaches like DeepLabCut 4 can excel. A recent preprint by Schuster and colleagues suggests a way forward using continuous home‐cage recording and DeepLabCut to gauge maternal presence in the nest 13 . Similarly, Winters and colleagues recently reported on the automation of the pup retrieval test 14 .…”