Biology subjects

Opendak, M.

Publications and source records attributed to Opendak, M..

4 recordsLinked to original sources

bioRxiv2026

Adversity severity shapes caregiving predictors and neural correlates of infant social behavior

Early-life adversity is associated with highly variable developmental outcomes, but identifying sources of this heterogeneity is difficult because variation in outcome is typically accompanied by variation in exposure. Animal models provide experimental leverage by standardizing features of the early environment while allowing variation in developmental experience and outcome to remain observable. Using a graded limited bedding and nesting model spanning normative rearing, moderate restriction, and severe scarcity, we asked what distinguishes social outcomes among animals exposed to the same resource restriction. Severe scarcity increased adverse maternal handling while leaving organized nurturing behaviors intact. Following the P8-P12 rearing manipulation, pups were tested outside the home cage in a P13 social approach assay. Severe scarcity reduced the proportion of pups that approached the dam, but outcomes varied substantially among scarcity litters. Greater typical maternal pup transport predicted greater approach, whereas a greater proportion of rough transport predicted poorer approach. Transport composition did not differ across rearing conditions, but its relationship with social behavior did. Amygdala intercalated-cell recruitment also covaried with social approach under severe scarcity despite limited condition-level differences in regional c-Fos. Plasma corticosterone differed across rearing conditions but did not covary detectably with the principal caregiving, behavioral, or neural measures. Maternal transport and intercalated-cell recruitment were not robustly associated, identifying separable experiential and neural correlates of behavioral variation. These findings show that standardizing an environmental constraint does not produce uniform developmental experience or outcome, and that caregiving experiences preserved across rearing conditions can distinguish social outcomes under severe scarcity.

neuroscience↗

bioRxiv2026

Bile acid signaling as a therapeutically tractable pathway linking early caregiving adversity to social behavior

Adverse early caregiving produces lasting changes in social behavior and increases vulnerability to psychiatric illness, yet the biological pathways through which these experiences become embedded during development remain poorly understood. Using two complementary rat models of early-life adversity (ELA), we combined behavioral phenotyping with serum metabolomics and basolateral amygdala (BLA) transcriptomics to identify bile acid biology as a candidate pathway associated with disrupted social development. In the Deconstructed Adversity Model (DAM), which dissociates adverse social experience from non-social stress, social adversity produced distinct behavioral alterations accompanied by sex-, age-, and adversity-dependent changes in peripheral bile acid and tryptophan metabolism together with sex-specific BLA gene co-expression networks associated with social behavior. These coordinated peripheral and central alterations converged on bile acid biology as a candidate pathway for pharmacological intervention. We next tested this prediction in the Scarcity Adversity Model via Limited Bedding (SAM-LB), where oral supplementation with chenodeoxycholic acid (CDCA), but not the related primary bile acid cholic acid (CA), during the adversity period rescued the infant affiliative social deficit produced by adverse caregiving. Together, these findings identify bile acid biology as a pharmacologically tractable pathway associated with the developmental consequences of adverse early caregiving and support further investigation of CDCA, an FDA-approved bile acid, as a candidate intervention for mitigating early social behavioral deficits.

neuroscience↗

bioRxiv2024

The lateral habenula integrates age and experience to promote social transitions in developing rats

Social behavior deficits are an early-emerging marker of psychopathology and are linked with early caregiving quality. However, the infant neural substrates linking early care to social development are poorly understood. Here, we focused on the infant lateral habenula (LHb), a highly-conserved brain region at the nexus between forebrain and monoaminergic circuits. Despite its consistent links to adult psychopathology, this brain region has been understudied in development when the brain is most vulnerable to environmental impacts. In a task combining social and threat cues, suppressing LHb principal neurons had opposing effects in infants versus juveniles, suggesting the LHb promotes a developmental switch in social approach behavior under threat. We observed that early caregiving adversity (ECA) disrupts typical growth curves of LHb baseline structure and function, including volume, firing patterns, neuromodulatory receptor expression, and functional connectivity with cortical regions. Further, we observed that suppressing cortical projections to the LHb rescued social approach deficits following ECA, identifying this microcircuit as a substrate for disrupted social behavior. Together, these results identify immediate biomarkers of ECA in the LHb and highlight this region as a site of early social processing and behavior control.

neuroscience↗

bioRxiv2019

Oxytocin Neurons Enable Social Transmission of Maternal Behavior

Maternal care is profoundly important for mammalian survival, and non-biological parents can express it after experience with infants. One critical molecular signal for maternal behavior is oxytocin, a hormone centrally released by hypothalamic paraventricular nucleus (PVN). Oxytocin enables plasticity within the auditory cortex, a necessary step for responding to infant vocalizations. To determine how this change occurs during natural experience, we continuously monitored homecage behavior of female virgin mice co-housed for days with an experienced mother and litter, synchronized with recordings from virgin PVN cells, including from oxytocin neurons. Mothers engaged virgins in maternal care by ensuring their nest presence, and demonstrated maternal behavior in self-generated pup retrieval episodes. These social interactions activated virgin PVN and gated behaviorally-relevant cortical plasticity for pup vocalizations. Thus rodents can acquire maternal behavior by social transmission, and our results describe a mechanism for adapting brains of adult caregivers to infant needs via endogenous oxytocin. One Sentence SummaryMother mice help co-housed virgins become maternal by enacting specific behaviors that activate virgin oxytocin neurons.

neuroscience↗