Fragmentation and high entropy of neonatal experience predict adolescent emotional outcome

Abstract

Vulnerability to emotional disorders including depression derives from interactions between genes and environment, especially during sensitive developmental periods. Across evolution, maternal care is a key source of environmental sensory signals to the developing brain, and a vast body of work has linked quantitative and qualitative aspects of maternal care to emotional outcome in children and animals. However, the fundamental properties of maternal signals, that promote advantageous vs pathological outcomes in the offspring, are unknown and have been a topic of intense study. We studied emotional outcomes of adolescent rats reared under routine or impoverished environments, and used mathematical approaches to analyze the nurturing behaviors of the dams. Unexpectedly, whereas the quantity and typical qualities of maternal care behaviors were indistinguishable in the two environments, their patterns and rhythms differed drastically and influenced emotional outcomes. Specifically, unpredictable, fragmented maternal care patterns translated into high-entropy rates of sensory signals to the offspring in the impoverished cages. During adolescence, these offspring had significant reductions in sucrose preference and in peer-play, two independent measures of the ability to experience pleasure. This adolescent anhedonia, often a harbinger of later depression, was not accompanied by measures of anxiety or helplessness. Dopaminergic pleasure circuits underlying anhedonia are engaged by predictable sequences of events, and predictable sensory signals during neonatal periods may be critical for their maturation. Conversely, unpredictability maternal-derived signals may disrupt these developmental processes, provoking anhedonia. In sum, high-entropy and fragmented patterns of maternal-derived sensory input to the developing brain predicts, and might promote, the development of anhedonia in rodents, with potential clinical implications.

Effects of early-life adversity on immune function are mediated by prenatal environment: Role of prenatal alcohol exposure

“…This inconsistency in maternal behavior introduces instability to an otherwise extremely stereotyped behavioral repertoire, altering the expected and required pattern of sensory stimulation received by the infant during a critical period of development. Inconsistency in maternal behavior has been previously observed using a more extreme early-life adversity model where the mother and litter are housed in a cage with a mesh bottom and provided with a single paper towel for nest building (Ivy et al, 2008; Molet et al, 2016). Importantly, the combination of increased negative maternal behavior, altered nursing behaviors, and inconsistent maternal behavior indicates that changes in maternal care were not limited to reductions in quantity and quality, but also to increased inconsistency in the pattern of care received from the caregiver in response to the insufficient bedding environment.…”

Early life stress accelerates behavioral and neural maturation of the hippocampus in male mice

“…For each assay (corticosterone, neurodevelopment, gene expression, and behavior), we took care to insure that animals from a minimum of two separate litters were sampled from. In previous studies of both mice and rats, elegant studies find that this manipulation leads to a fragmentation in maternal care and elevations in stress hormones in the dam (Molet et al, 2016; Rice et al, 2008; and Avishai-Eliner et al, 2001). Specifically, in those reports, the authors observed an increase in the number of departures from the nest by the dam, but no change in licking and grooming or arched back nursing (Molet et al, 2016).…”

“…In previous studies of both mice and rats, elegant studies find that this manipulation leads to a fragmentation in maternal care and elevations in stress hormones in the dam (Molet et al, 2016; Rice et al, 2008; and Avishai-Eliner et al, 2001). Specifically, in those reports, the authors observed an increase in the number of departures from the nest by the dam, but no change in licking and grooming or arched back nursing (Molet et al, 2016). As maternal behavior is difficult to assess mice, in part due to their small size and lack of stereotyped nursing posture, we did not carry out detailed assessment of maternal behavior, and instead relied on our successful replication of other core features of this paradigm, which includes growth restriction of litters.…”

Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks

“…Notably, there is little evidence of physical stress of the pups, with no hypothermia and minimal weight changes . Thus, the early-life stress that is engendered seems to be a direct result of the fragmented, unpredictable sensory signals from the mothers (Moriceau et al 2009;Baram et al, 2012;Molet et al, 2014Molet et al, , 2015a. These seem to provoke chronic early-life stress, including persistent elevation of plasma corticosterone and adrenal hypertrophy (Gilles et al, 1996;Rice et al, 2008).…”