Biology subjects

Oline, S. N.

Publications and source records attributed to Oline, S. N..

3 recordsLinked to original sources

bioRxiv2025

Erythropoietin alleviates intellectual disability and autism-like behavior of mice caused by Zbtb20 haploinsufficiency, a construct-valid model of Primrose syndrome

Among the known genetic causes of syndromic autism spectrum disorders (ASD) are transcription factor deficiencies. In this regard, haploinsufficiency of the zinc finger and broad complex, tramtrack, bric and brac domain-containing protein 20 (ZBTB20) leads to a prototypical clinical picture, referred to as Primrose syndrome, comprising severe ASD symptoms together with intellectual disability. Here, we present a comprehensive behavioral and phenotypical characterization of Zbtb20+/- mice, a construct valid model of this thus far untreatable human condition. Zbtb20+/- mice exhibit diminished sociability, reduced vocalization, distinct repetitive behaviors, impaired cognitive flexibility, hyperactivity and hypoalgesia. Magnetic resonance imaging reveals increased volumes of hippocampus, cerebellum, brain matter, and whole brain, confirmed by postmortem brain weight measurements. Due to our previous observation of enhanced ZBTB20 expression in CA1 pyramidal neurons upon recombinant human erythropoietin (rhEPO) injections, we anticipated a mitigating effect through rhEPO treatment of Zbtb20 deficiency/Primrose syndrome. Indeed, after three weeks of alternate-day rhEPO injections, a remarkable improvement in the behavioral phenotype was observed. Our results highlight rhEPO as a first promising treatment for Primrose syndrome.

neuroscience↗

bioRxiv2025

An automated two-choice social operant task for probing moment-to-moment changes in social satiety

In naturalistic conditions, animals must routinely make ongoing self-motivated choices about whether to initiate interactions with same or opposite-sex partners and whether to re-initiate social contact when interactions have ended. However, it remains unclear what governs these choices, and whether they are motivated by drive states that exhibit signatures of moment-to-moment social satiety when these interactions have ended. Here, to explicitly test this at the behavioral level, we designed a novel fully-automated two-choice social operant paradigm where individuals can choose between same and opposite-sex social rewards and rewards are delivered for interaction with systematically varying durations. We trained cohorts of both sexes on this task and quantified the patterns of choices. We used choice latency as a metric to infer moment-to-moment satiety to test whether increased interaction duration leads to increased moment-to-moment satiety. We find that although both males and females have stable choice biases across sessions, with males showing consistent opposite sex biases, only males exhibit behavioral signatures of moment-to-moment social satiety and are sensitive to the duration of interaction. Using a simple normative model to capture patterns of social choice, we observe that behavior is better fit by a model that has a single evolving social drive and choice bias, rather than a model with multiple, independent drives for same and opposite-sex interactions. Together, our data reveal behavioral signatures of social satiety and offer new insights into the underlying homeostatic and motivational drives that govern social choices.

neuroscience↗

bioRxiv2024

Coordinated cross-brain activity during accumulation of sensory evidence and decision commitment

Decision-making is thought to involve two phases: first, evidence accumulation, then, decision commitment. Accumulation is represented broadly in the brain, but whether this best matches single versus multiple accumulator models is unknown. Here, analysis of simultaneous, bilateral recordings across sensory, association, and motor regions, in both cortex and subcortical structures, strongly supports a single accumulator, and suggests that accumulated noise (diffusion) originates frontally. Decision commitment can occur internally, without an overt report. Long-standing competing models of covert commitment disagree as to whether it is abrupt or continuous. Temporally aligning data on a single-trial estimator of internal, covert commitment ("nTc") revealed a rapid ([≤]50 ms) drop in the accumulators sensitivity to incoming sensory evidence, favoring abrupt transition models, and indicating a discrete cross-brain state change at nTc that was first detectable in motor regions. These data discriminate between decades-old models of accumulation, and between decades-old models of the transition to commitment.

neuroscience↗