Biology subjects

Bangasser, D. A.

Publications and source records attributed to Bangasser, D. A..

5 recordsLinked to original sources

bioRxiv2026

Adapting Social Operant Paradigms to Measure Postpartum Maternal Motivation

Operant paradigms are powerful tools to quantify motivation and reward. Traditionally, operant conditioning research has been limited to food and drug reinforcers. Recent advances in commercially available operant equipment, however, allow for the quantification of social motivation. These operant assays are an improvement over commonly used social preference tasks, as they enable direct measurement of the effort and motivation driving social behavior. Based on a design by Venniro et al. (2020), the MedPC social operant boxes modify the traditional operant box setup for social interactions. The experimental rat can lever-press to raise a door for an interaction with a target rat behind a porous barrier. These social operant boxes have been widely adapted to test social behavior in adult and adolescent rodents and investigate how a range of conditions (e.g. stress, drug taking, etc.) affect social motivation. However, there is a gap in assessing maternal motivation for pups during the postpartum period, despite ample evidence that postpartum social behavior is highly relevant for offspring health outcomes. Here, we detail 3D-printed modifications to the standard Med PC social operant boxes to adapt the social target chamber to safely house neonatal pups. We have also developed testing protocols to assess motivation during the limited postpartum period. These data demonstrate that, with simple modifications to social operant chambers and testing protocols, the field can implement advanced behavioral approaches to directly assess maternal motivation.

animal behavior and cognition↗

bioRxiv2026

Early life adversity disrupts adult social reward motivation

Early life adversity can produce persistent changes during development that increase vulnerability to neuropsychiatric disorders. Although disruptions in reward processing are widely recognized as a hallmark of these disorders, reward is not a single construct. Distinct forms of reward including social interaction and primary rewards such as food rely on overlapping but dissociable neural circuitry and may be differentially affected by adverse experiences. Here, we used a rodent model of neonatal predator odor exposure (POE) to determine how early life threat influences motivation for social and sucrose reward in adulthood using operant procedures. Neonatal POE reduced adult motivation for a social reinforcer during an operant social self-administration task, whereas motivation for a sucrose reinforcer was unchanged. However, we did find a significant difference in sucrose self-administration with POE females pressing more for sucrose than control females. These findings demonstrate that neonatal threat does not produce a generalized deficit in motivation but rather selectively alters motivation across distinct reward domains. Together, this work identifies social reward as a particularly vulnerable behavioral domain following early life threat and provides new insight into how adverse developmental experiences shape adult reward-related behavior.

animal behavior and cognition↗

bioRxiv2026

Early resource scarcity drives persistent transcriptional changes and vascular remodeling in the female prefrontal cortex

Early childhood poverty is an environmental risk factor for psychiatric and neurodegenerative disorders, yet the cellular mechanisms by which resource scarcity produces persistent brain vulnerability remain poorly understood. The medial prefrontal cortex (mPFC), which regulates executive function and motivated behavior, is sensitive to early environmental conditions. To identify mechanisms linking early resource scarcity to lasting mPFC dysfunction, we used the rat limited bedding and nesting (LBN) model, which recapitulates key features of poverty. Prior work shows LBN disrupts mPFC-mediated behaviors in adulthood, often in a sex-specific manner. Here, we used single-nucleus RNA sequencing (snRNAseq) to identify sex- and cell-type-specific transcriptional alterations in the adult mPFC following brief postnatal LBN exposure or control housing. LBN induced more differentially expressed genes (DEGs) across multiple pyramidal neuron clusters in females than in males. Unexpectedly, the largest transcriptional changes due to LBN occurred in vascular cells in females, whereas male vascular cells exhibited no DEGs. These female-specific vascular genes were enriched for alterations of transcriptional programs regulating angiogenesis and endothelial structure. This molecular profile was orthogonally validated with 3D vascular reconstruction, revealing LBN reduced vascular coverage in the adult female mPFC, driven by decreased vessel volume and shortened vessel length, while males were unaffected. Reduced vascular coverage may constrain metabolic support to this region. The postnatal period is a critical window for vascular maturation, and, taken together, these findings identify persistent, female-specific vascular alterations as a novel and previously unrecognized mechanism through which early resource scarcity may persistently affect brain function and vulnerability.

neuroscience↗

bioRxiv2026

Hypothalamus amyloid levels are associated with early sex-dependent alterations in energy homeostasis in TgF344-AD rats

We reported previously that diet-induced obesity exacerbates early-stage Alzheimers disease (AD)-like pathology in TgF344-AD rats. Our findings also suggested that TgF344-AD rats may be prone to weight gain during early AD development, which we assessed here. Energy intake, body composition, and the impact of glucose administration on blood glucose were also assessed. Body temperature, intrascapular brown adipose tissue (iBAT) mass, and iBAT uncoupling protein-1 (UCP1) expression were used as indicators of thermogenic function. Soluble amyloid {beta}40 (A{beta}40) and A{beta}42 were quantified in hypothalamus. Male TgF344-AD rats began to outweigh wildtype (WT) littermates by 5 weeks of age; this increase emerged later in female TgF344-AD rats (~5 months). Female TgF344-AD rats ingested more energy from chow and a high fat, high sugar (HFHS) diet, gained more weight on the HFHS diet, and had lower UCP1 than WT rats, effects not observed in male TgF344-AD rats. Surprisingly, male and female TgF344-AD rats had increased body temperatures. This was restricted to the dark phase in females, which is when they ingest excess calories. Finally, the HFHS diet disrupted glucose regulation in male but not female TgF344-AD rats. These findings suggest that increases in energy intake and decreases in UCP1 may contribute to the additional weight gain in female TgF344-AD rats. The causes for these increases in males remain unclear. Hypothalamic A{beta}42 correlated with glucose dysregulation in male TgF344-AD rats and BAT mass in female TgF344-AD rats, raising the possibility that increases in A{beta}42 in hypothalamus produce sex-specific disruptions in energy homeostasis.

neuroscience↗

bioRxiv2023

Early resource scarcity causes cortical astrocyte enlargement and sex-specific changes in the orbitofrontal cortex transcriptome in adult rats

Astrocyte morphology affects function, including the regulation of glutamatergic signaling. This morphology changes dynamically in response to the environment. However, how early life manipulations alter adult cortical astrocyte morphology is underexplored. Our lab uses brief postnatal resource scarcity, the limited bedding and nesting (LBN) manipulation, in rats. We previously found that LBN promotes later resilience to adult addiction-related behaviors, reducing impulsivity, risky decision-making, and morphine self-administration. These behaviors rely on glutamatergic transmission in the medial orbitofrontal (mOFC) and medial prefrontal (mPFC) cortex. Here we tested whether LBN changed astrocyte morphology in the mOFC and mPFC of adult rats using a novel viral approach that, unlike traditional markers, fully labels astrocytes. Prior exposure to LBN causes an increase in the surface area and volume of astrocytes in the mOFC and mPFC of adult males and females relative to control-raised rats. We next used bulk RNA sequencing of OFC tissue to assess transcriptional changes that could increase astrocyte size in LBN rats. LBN caused mainly sex-specific changes in differentially expressed genes. However, Park7, which encodes for the protein DJ-1 that alters astrocyte morphology, was increased by LBN across sex. Pathway analysis revealed that OFC glutamatergic signaling is altered by LBN in males and females, but the gene changes in that pathway differed across sex. This may represent a convergent sex difference where glutamatergic signaling, which affects astrocyte morphology, is altered by LBN via sex-specific mechanisms. Collectively, these studies highlight that astrocytes may be an important cell type that mediates the effect of early resource scarcity on adult brain function.

neuroscience↗