Biology subjects

Libster, A. M.

Publications and source records attributed to Libster, A. M..

4 recordsLinked to original sources

bioRxiv2026

Reln haploinsufficiency alters fentanyl-induced striatal activity and adaptive responding without affecting opioid reinforcement

The Reln gene encodes the extracellular glycoprotein Reelin that regulates synaptic plasticity and activity-dependent gene expression with implications in several neuropsychiatric disorders, including substance use disorder. While reduced Reln expression alters responses to psychostimulants and cannabinoid, its role in opioid-related behaviors remains unknown. Here, we examined whether Reln haploinsufficiency modifies behavioral and molecular responses to the synthetic opioid fentanyl. Heterozygous Reeler (Reln+/-) mice and wild-type littermates were assessed using using complementary contingent and non-contingent models of fentanyl exposure, including multi-phase fentanyl intravenous self-administration paradigm, conditioned place preference paradigm, locomotor assay, and dorsal striatal immediate early gene expression. Reln haploinsufficiency did not alter acquisition, extinction, or cue-induced reinstatement during self-administration, indicating stable opioid reinforcement and relapse-like behavior. Progressive ratio testing revealed a sex-dependent effect in which male Reln+/- mice showed reduced motivation for fentanyl compared to male wild-type mice. In contrast, following passive fentanyl exposure, Reln+/- mice exhibited enhanced fentanyl-induced locomotion and increased Fos immunoreactivity in the dorsal striatum, while CPP remained unchanged. Together, these findings demonstrate that Reln haploinsufficiency does not substantially modify opioid reinforcement or cue-driven drug seeking but enhances acute pharmacological sensitivity to fentanyl. These results identify Reln as a modulatory factor in opioid-responsive neural circuits that preferentially influences acute drug-evoked neuronal activation rather than the associative learning processes underlying opioid reinforcement.

neuroscience↗

bioRxiv2025

The development of FEDUPP: Feeding Experimentation Device Users Processing Package to Assess Learning and Cognitive Flexibility

Cognitive flexibility, the ability to adapt behavior in response to changing contingencies, is a key component of adaptive decision-making and is impaired in multiple neuropsychiatric disorders. Traditional rodent assays of cognitive flexibility are conducted in experimenter-controlled sessions in restrictive environments, limiting ecological validity and temporal resolution. Here, we developed a fully automated, home-cage paradigm using the Feeding Experimentation Device 3 (FED3) and a companion open-source analysis pipeline, the Feeding Experimentation Device Users Processing Package (FEDUPP), to assess learning and cognitive flexibility with minimal experimenter intervention. The paradigm combines a single-day fixed-ratio 1 (FR1) task with a multi-day, reversal learning task in which active port assignment switches every 25 pellets collected. FEDUPP implements multi-scale learning metrics, including overall accuracy, an 80% accuracy milestone, and a machine learning-based classification of meal accuracy to capture motivated, goal-directed feeding. In wild-type mice, the paradigm detected rapid FR1 acquisition and progressive within-block adaptation during reversal. Application to mice with dorsal hippocampal knockdown of the scaffolding protein CASK revealed faster FR1 acquisition and higher accuracy than controls but a delayed onset of the first accurate meal after reversal, suggesting a selective deficit in updating goal-directed feeding behavior. These findings demonstrate that FEDUPP enables high-resolution, continuous assessment of learning and cognitive flexibility in ethologically relevant settings, and that meal-based accuracy provides a sensitive metric for detecting subtle flexibility impairments not captured by traditional measures.

animal behavior and cognition↗

bioRxiv2024

The attenuation of activity-based anorexia by obese adipose tissue transplant is AgRP neuron-dependent.

Anorexia nervosa (AN) is an eating disorder observed primarily in girls and women, and is characterized by a low body mass index, hypophagia, and hyperactivity. The activity-based anorexia (ABA) paradigm models aspects of AN, and refers to the progressive weight loss, hypophagia, and hyperactivity developed by rodents exposed to time-restricted feeding and running wheel access. Recent studies identified white adipose tissue (WAT) as a primary location of the metabolic memory of prior obesity, and implicated WAT-derived signals as drivers of recidivism to obesity following weight loss. Here, we tested whether an obese WAT transplant could attenuate ABA-induced weight loss in normal female mice. Recipient mice received a WAT transplant harvested from normal chow-fed, or HFD-fed obese mice; obese fat recipient (OFR) and control fat recipient (CFR) mice were then tested for ABA. During ABA, OFR mice survived longer than CFR mice, defined as maintaining 75% of their initial body weight. Next, we tested whether agouti-related peptide (AgRP) neurons, which regulate feeding behavior and metabolic sensing, mediate this effect of obese WAT transplant. CFR and OFR mice received either control or neonatal AgRP ablation, and were assessed for ABA. OFR intact mice maintained higher body weights longer than CFR intact mice, and this effect was abolished by neonatal AgRP ablation; further, ablation reduced survival in OFR, but not CFR mice. In summary, obese WAT transplant communicates with AgRP neurons to increase body weight maintenance during ABA. These findings encourage the examination of obese WAT-derived factors as potential treatments for AN.

neuroscience↗

bioRxiv2018

Acute Food Deprivation Rapidly Modifies Valence-Coding Microcircuits in the Amygdala

In the quest for food, we may expend effort and increase our vulnerability to potential threats. Motivation to seek food is dynamic, varying with homeostatic need. What mechanisms underlie these changes? Basolateral amygdala neurons projecting to the nucleus accumbens (BLA[->]NAc) preferentially encode positive valence, whereas those targeting the centromedial amygdala (BLA[->]CeM) preferentially encode negative valence. Longitudinal in vivo two-photon calcium imaging revealed that BLA[->]NAc neurons were more active, while BLA[->]CeM neurons were less active, following just 1 day of food deprivation. Photostimulating BLA[->]CeM neurons inhibited BLA[->]NAc neurons at baseline, but food deprivation rapidly converted this inhibition into facilitation, supporting a model wherein BLA[->]NAc excitability mediates invigorated food-seeking behavior after deprivation. Indeed, inhibiting BLA[->]NAc reduced motivation for a caloric reinforcer in food deprived animals. Taken together, negative valence overrides positive valence processing in satiety, but changing homeostatic needs alter reward value via a rapid shift in the balance between projection-defined populations of BLA neurons.

neuroscience↗