Biology subjects

Miller-Crews, I.

Publications and source records attributed to Miller-Crews, I..

5 recordsLinked to original sources

bioRxiv2026

Single-Nucleus Transcriptomics of the Mouse Medial Preoptic Area Reveals Sex-Dependent Molecular Signatures of Social Dominance

Social dominance hierarchies are a common form of social organization across animal species. We have previously shown that both male and female CD-1 mice form highly linear dominance hierarchies. In mice and other vertebrates, the medial preoptic area (mPOA) is a key hypothalamic sub-region regulating aggressive and defensive behaviors that support hierarchical social structures, but the transcriptional mechanisms in mPOA neurons underlying dominance behaviors and the influence of sex on these neuron populations in the context of social dominance hierarchies remain largely unresolved. Using single-nucleus RNA sequencing (snRNA-seq) to profile mPOA neurons from dominant and subordinate mice, we identified highly consistent social status-dependent changes in the transcriptomes of neuronal nuclei expressing neuropeptide transcripts. Oxytocin expression was remarkably widespread across mPOA neurons, and we found it to be the primary driver of group differences in neuropeptide co-expression networks. Overall, dominant males and females exhibited markedly decreased expression of oxytocin and vasopressin and had a lower proportion of neurons co-expressing multiple neuropeptide transcripts compared to subordinate individuals. In contrast, subordinates displayed widespread reorganization of the transcriptomic neuropeptidome and strikingly enhanced coupling of neuropeptide expression in mPOA neurons. Despite the strong pattern of concordant gene expression in dominant and subordinate individuals, the number of genes that were differentially expressed by status was substantially reduced in males compared to females. In sum, these results demonstrate that maintenance of social status dynamically reconfigures hypothalamic transcriptomic neuropeptidome in a sex-dependent manner and establishes how social status is encoded at a single-cell resolution.

neuroscience↗

bioRxiv2025

How sex shapes transcriptome evolution in the songbird brain

Sex differences have long captivated scientists, yet the evolutionary rate of change in sex-biased gene expression has not been directly quantified. To address this issue, we introduce new options in CAGEE (Computational Analysis of Gene Expression Evolution), specifically unbounded Brownian motion and variable evolutionary rates among genes. We applied these features to brain transcriptomes of ten songbird species, half of which convergently evolved obligate cavity-nesting, an element of reproductive ecology linked to sex-specific changes in competitive behavior. We find that the degree of sex-bias - measured as male:female expression ratio for each gene - evolves twice as fast on the Z chromosome versus autosomes, but Z gene expression does not evolve at different rates among sexes. Most Z-linked genes are male-biased in their expression, but not all. These sex-balanced genes are not skewed in their rate of evolution, contrary to the hypothesis that some genes experience selection for balance and consequently evolve more slowly. Finally, the degree of sex-bias in gene expression evolves more quickly along obligate-cavity nesting lineages, suggesting that sex-specific selection may shape the evolution of brain sex differences, or lack thereof. Together, these results provide new insights into the interplay between sex and gene expression evolution.

evolutionary biology↗

bioRxiv2025

AI, citizen science, and the 2024 eclipse emphasize the importance of light for bird behavior

On April 8th 2024, a total solar eclipse disrupted light-dark cycles for North American birds during the lead-up to spring reproduction. Compiling over 10,000 community observations and AI analyses of nearly 100,000 vocalizations, we found that bird behavior was significantly affected by these few minutes of unexpected afternoon darkness. More than half of wild bird species changed their biological rhythms, with many producing a dawn chorus in the aftermath of the eclipse. This natural experiment demonstrates the power of technology-enabled and public science projects to understand our natural world. Further, it underscores the power of light in structuring animal behavior: even when night lasts for just four minutes, robust behavioral changes ensue.

animal behavior and cognition↗

bioRxiv2024

Single-nuclei transcriptomes in the hypothalamus and POA of a highly social cichlid

Complex behavioral phenotypes, such as social status, emerge from the genome across biological levels, with many of the fundamental neural mechanisms shared across vertebrates. While various aspects of the brain have been implicated in modulating social behavior, critical regulators include cells of the preoptic area (POA) and hypothalamus, which by applying cellular- resolution transcriptomic approaches allows for greater exploration of cellular dynamics in these cells. Yet, how complex gene networks function between and within cell types to regulate complex social behavior is still poorly understood. Importantly, when considering functionally relevant neuronal classes of genes such as neuropeptides, understanding the inherent complexity that emerges from the interaction of these genes in the transcriptomic neuropeptidome can provide unique insight into how social behavior is regulated. Here, we used single-nucleus RNA-sequencing in the hypothalamus and POA of a highly social cichlid fish, Astatotilapia burtoni, to understand the effect that social status has on cellular-level transcriptomic profiles. Males of this species are well known for their highly plastic phenotypes related to social status, which allows for a hypothesis-driven approach. We demonstrate how social status manifests in changes of gene co-expression networks across neuronal populations and highlight transcriptomic signatures of social dominance when targeting known functional differences among AVP neuronal cell types. We implement a novel approach to relate how differences in social state translate to the integration of the transcriptomic neuropeptidome. Taken together, this research provides insights into how gene expression networks that modulate social behavior, including neuropeptide networks, function at the cellular level. Significance StatementHere, we used single-nucleus RNA-seq in the hypothalamus and POA of Astatotilapia burtoni to understand the effect that social status has on cellular gene expression. We demonstrate how social status manifests, from changes in broader neuronal gene networks to targeted changes between known socially-relevant neurons. For the first time, we assess the entirety of the transcriptomic neuropeptidome to understand the interaction of neuropeptide gene networks with social dominance. These findings provide a valuable resource for future functional work and an analytical framework for comparative studies on the evolution of the neural mechanisms of social behavior. Insights into the transcriptomic networks that modulate social status, specifically with neuropeptides, aid in our understanding of the complexity inherent in social behavior.

neuroscience↗

bioRxiv2024

Extinction Training Suppresses Activity of Fear Memory Ensembles Across the Hippocampus and Alters Transcriptomes of Fear-Encoding Cells

Contextual fear conditioning has been shown to activate a set of "fear ensemble" cells in the hippocampal dentate gyrus (DG) whose reactivation is necessary and sufficient for expression of contextual fear. We previously demonstrated that extinction learning suppresses reactivation of these fear ensemble cells and activates a competing set of DG cells - the "extinction ensemble." Here, we tested whether extinction was sufficient to suppress reactivation in other regions and used single nucleus RNA sequencing (snRNA-seq) of cells in the dorsal dentate gyrus to examine how extinction affects the transcriptomic activity of fear ensemble and fear recall-activated cells. Our results confirm the suppressive effects of extinction in the dorsal and ventral dentate gyrus and demonstrate that this same effect extends to fear ensemble cells located in the dorsal CA1. Interestingly, the extinction-induced suppression of fear ensemble activity was not detected in ventral CA1. Our snRNA-seq analysis demonstrates that extinction training markedly changes transcription patterns in fear ensemble cells and that cells activated during recall of fear and recall of extinction have distinct transcriptomic profiles. Together, our results indicate that extinction training suppresses a broad portion of the fear ensemble in the hippocampus, and this suppression is accompanied by changes in the transcriptomes of fear ensemble cells and the emergence of a transcriptionally unique extinction ensemble.

neuroscience↗