Biology subjects

Manoli, D. S.

Publications and source records attributed to Manoli, D. S..

6 recordsLinked to original sources

bioRxiv2026

Spatial transcriptomics implicates the thalamus and cortex in autism and schizophrenia

The past decade has seen tremendous progress in the identification of genes associated with complex neuropsychiatric disorders, including autism spectrum disorder (ASD) and schizophrenia. Expression patterns of these genes in single cell data strongly implicate excitatory and inhibitory neurons; however, there are limited data on the brain regions involved - a critical question for neurobiology. Spatial transcriptomics provide an opportunity to perform systematic multiregional analyses to provide insights into this question. Here, we have generated a spatial transcriptomics dataset encompassing the diverse anatomical territories of the adult mouse brain sagittal midsection. We compare neuropsychiatric gene enrichment by applying Gene Fraction Enrichment Score (GFES), a novel statistic method that controls for differing neuronal proportions across regions. ASD-associated genes identified by exome sequencing were most enriched in the thalamus followed by the cortex. Schizophrenia genes from genome-wide association studies were also enriched in the thalamus, along with the hippocampus and cortex. These findings add to the evidence that the thalamus plays a major role in neuropsychiatric disorders whilst supporting roles for the cortex and hippocampus. The results highlight shared and distinct patterns for pleiotropic brain disorders that could elucidate common underlying mechanisms and circuitry.

neuroscience↗

bioRxiv2026

Single-library chromosome-scale diploid assemblies of vole genomes resolve a species-specific duplication implicated in pair bonding

Comparing prairie voles (Microtus ochrogaster), a species that forms lasting pair bonds and exhibits biparental care, with meadow voles (Microtus pennsylvanicus), a non-monogamous species showing maternal care only, provides a framework to examine the genomic basis of behavioral divergence over short evolutionary time. Here, we develop a simplified assembly approach combining PacBio HiFi and CiFi sequencing in a single library and run, producing high-quality contiguous chromosome-scale diploid prairie and meadow vole genomes (2.3 Gbp). Comparative analysis reveals substantial differences, including near-complete Y chromosome divergence and a prairie-vole-specific duplication of Avpr1a, a vasopressin receptor gene implicated in social bonding and autism in humans. These extensive genomic changes suggest rapid chromosome evolution as a driver of the dramatic Microtus radiation, generating [~]60 vole species in >2 million years. This single-library approach facilitates a simplified and more affordable assembly workflow, producing near-complete genomes of diverse species using one sequencing platform.

genomics↗

bioRxiv2025

Identity-stable multi-animal tracking using bidirectional segmentation with object-level memory

Tracking animal behavior in naturalistic settings is essential for understanding social dynamics and their neural underpinnings. Pose estimation methods can produce accurate keypoints using framewise inference. However, post hoc tracking steps often struggle to maintain consistent identity over time, particularly during close and rapid social interactions between visually similar animals. We present a pipeline for bidirectional video object segmentation (VOS) to correct identity swaps with much less manual annotation effort, addressing the prohibitive cost of identity correction of pose estimation data in long recordings and large cohorts. Our approach makes use of a state-of-the-art VOS algorithm, Cutie, which leverages both pixel- and object-level representations across multiple memory timescales. By comparing segmentation masks from independent forward and reverse inference runs, we identify localized zones of disagreement and flag them for manual review. When applied to more than 160 hours of dyadic vole interaction videos, our method reduces identity swaps by two orders of magnitude compared to typical pose estimation workflows and requires review of less than 0.3% of frames per video to achieve identity error-free segmentation masks and aligned keypoints. Our approach generalizes to social interactions involving three or more animals, with scalability constrained primarily by behavioral complexity (e.g., complete occlusion of multiple individuals). Our method enables scalable, long-term tracking of unmarked animals in group settings and provides a practical foundation for more naturalistic studies of social behavior. To lower the barrier for researchers facing similar tracking challenges, we provide an accessible graphical user interface for general use.

animal behavior and cognition↗

bioRxiv2025

Oxytocin receptor absence reduces selectivity in peer relationships and alters neurochemical release dynamics in prairie voles

Abstract/SummaryFriendships, or selective peer relationships, are a vital component of healthy social functioning in humans, while deficits in these relationships are associated with negative physical and mental health consequences. Like humans, prairie voles are among the few mammalian species that form selective social bonds with both peers and mates, making them an excellent model for the mechanistic investigation of selective social attachment. Here, we explored the role of oxytocin receptors in selective peer attachment using prairie voles lacking a functional oxytocin receptor gene (Oxtr1-/-). We found that Oxtr1-/- animals exhibited significant delays in peer relationship formation compared to wildtype animals. Oxytocin receptor function also contributed to the maintenance of peer bonds, as Oxtr1-/- voles displayed reduced relationship stability and lost selective attachments rapidly in a multi-chamber, group-living habitat. Oxtr1-/- voles also showed deficits in both general social reward as well as selective social reward for a peer partner over an unfamiliar conspecific. Evoked oxytocin release in the nucleus accumbens was reduced in Oxtr1-/- animals compared to their wildtype counterparts, indicating that these voles do not have a compensatory increase in oxytocinergic signaling. Together, these data indicate that oxytocin receptors influence the formation, persistence, and reward value of peer relationships.

animal behavior and cognition↗

bioRxiv2024

Oxytocin receptor controls distinct components of pair bonding and development in prairie voles

Oxytocin receptor (Oxtr) signaling influences complex social behaviors in diverse species, including social monogamy in prairie voles. How Oxtr regulates specific components of social attachment behaviors and the neural mechanisms mediating them remains unknown. Here, we examine prairie voles lacking Oxtr and demonstrate that pair bonding comprises distinct behavioral modules: the preference for a bonded partner, and the rejection of novel potential mates. Our longitudinal study of social attachment shows that Oxtr sex-specifically influences early interactions between novel partners facilitating the formation of partner preference. Additionally, Oxtr suppresses promiscuity towards novel potential mates following pair bonding, contributing to rejection. Oxtr function regulates coordinated patterns of gene expression in regions implicated in attachment behaviors and regulates the expression of oxytocin in the paraventricular nucleus of the hypothalamus, a principal source of oxytocin. Thus, Oxtr controls genetically separable components of pair bonding behaviors and coordinates development of the neural substrates of attachment.

neuroscience↗

bioRxiv2022

Oxytocin receptor is not required for social attachment in prairie voles

Prairie voles are among a small group of mammals that display long-term social attachment between mating partners. Many pharmacological studies show that signaling via the oxytocin receptor (OxtR) is critical for the display of social monogamy in these animals. We used CRISPR-mutagenesis to independently generate three different OxtR null mutant prairie vole lines. OxtR mutants displayed social attachment such that males and females showed a behavioral preference for their mating partners over a stranger of the opposite sex when assayed using different paradigms. Mothers lacking OxtR delivered viable pups, and parents displayed care of their young and raised them to the weanling stage. Together, our studies unexpectedly reveal that OxtR-mediated signaling is genetically dispensable for social attachment, parturition, and parental behavior.

animal behavior and cognition↗