Biology subjects

Colquitt, B. M.

Publications and source records attributed to Colquitt, B. M..

6 recordsLinked to original sources

bioRxiv2026

Gene regulatory co-option drives birdsong neural circuit specialization

As animals evolve complex motor skills, they acquire more diverse supporting motor circuits in their nervous systems. Yet the molecular mechanisms driving motor circuit evolution remain poorly understood. Birdsong, a learned complex motor skill with parallels to human speech, is controlled by a dedicated neural circuit - the song system - that is distinguished from nearby sensorimotor regions by molecular, physiological, and connectivity specializations. By profiling gene expression and chromatin accessibility in the songbird brain, we found that each projection neuron type in the song system has a molecularly similar sister neuron type in adjacent non-song regions; these sister neurons lack specialized gene expression and are transcriptionally similar to neurons in the chicken brain. The gene regulatory networks (GRNs) controlled by transcription factors MAFB and EMX2, typically active in fast-spiking interneurons and astrocytes, are specifically active in song-dedicated extratelencephalic projection neurons. Furthermore, the heterologous expression of MAFB or EMX2 in chicken projection neurons was sufficient to drive expression programs characteristic of song neurons. These results support a model in which song-dedicated neurons emerged from ancestral neural types in part through the co-option of GRNs active in other cellular contexts, providing a genetic mechanism underlying the evolution of birdsong.

neuroscience↗

bioRxiv2025

MALDI-FISH for co-localization of brominated metabolites and Pseudovibrio spp. in Aplysina tissue

Bromotyrosine-containing natural products have long been isolated from marine sponges of the order Verongiida. Recent studies have questioned the source of these natural products whether production occurs through the sponge, its diverse microbiota, or perhaps a combination of both. While studying the uptake of engineered bacterial strains by sponges, we have observed production of fistularin-3 in sponge. To explore these results further, we employed multimodal imaging techniques to co-localize microbial metabolites with fluorescent in situ hybridization (FISH) probes. Here, we built on previously developed MALDI-FISH methods to add to the conversation on brominated metabolite production in marine sponges. Using MALDI-MSI, we measured fistularin-3, a poly-brominated natural product previously isolated from Aplysina aerophoba, present in our A. aerophoba samples that were inoculated with Pseudovibrio brasiliensis. A recent study reported that P. brasiliensis produced fistularin-3 in pure culture, but this data has not yet been reproduced. We employed MALDI-MSI and FISH on the same sponge cryosections to colocalize the spatial distribution of fistularin-3 with P. brasiliensis in sponge tissue. Despite the caveats of this study, our data suggests that perhaps both sponge and microbe may be required for production of fistularin-3.

microbiology↗

bioRxiv2025

An interneuronal CRH and CRHBP circuit stabilizes birdsong performance

The performance of skilled behaviors requires a balance between consistency and adaptability. Although the neural mechanisms that regulate this balance have been extensively studied at systems and physiological levels, relatively little is known about how the molecular properties of motor circuits influence motor stability versus flexibility. Here, we characterize the region- and cell-type specific expression patterns of neuropeptide systems across the neural circuit that controls the learning and performance of birdsong, a model for skilled behavior. We identify a number of neuropeptide pathways with differential expression between song regions and surrounding areas that are not involved in song production or learning. One of the strongest enriched genes in song regions is corticotropin releasing hormone binding protein (CRHBP), whose product binds corticotropin releasing hormone (CRH), a neuropeptide implicated in neuronal excitability and plasticity. We find that the expression of CRHBP in the song motor pathway decreases upon deafening-induced song destabilization, increases during song acquisition, and increases the more a bird sings. CRH and CRHBP are expressed in distinct interneuronal populations in song motor regions, providing a local neuromodulatory circuit well-positioned to regulate song performance. Consistent with this role, genetic and pharmacological manipulation of the CRH pathway in the song motor pathway resulted in bidirectional modifications of song variability, with elevated CRHBP acting to maintain low variability and elevated CRH acting to increase variability. These data indicate that an interneuronal neuropeptidergic pathway maintains the stability of song, acting as a local mechanism that regulates the balance between motor consistency versus flexibility.

neuroscience↗

bioRxiv2025

Self-Organizing Neural Networks in Organoids Reveal Principles of Forebrain Circuit Assembly

The mouse cortex is a canonical model for studying how functional neural networks emerge, yet it remains unclear which topological features arise from intrinsic cellular organization versus external regional cues. Mouse forebrain organoids provide a powerful system to investigate these intrinsic mechanisms. We generated dorsal (DF) and ventral (VF) forebrain organoids from mouse pluripotent stem cells and tracked their development using longitudinal electrophysiology. DF organoids showed progressively stronger network-wide correlations, while VF organoids developed more refined activity patterns, enhanced small-world topology, and increased modular organization. These differences emerged without extrinsic inputs and may be driven by the increased generation of Pvalb+ interneurons in VF organoids. Our findings demonstrate how variations in cellular composition influence the self-organization of neural circuits, establishing mouse forebrain organoids as a tractable platform to study how neuronal populations shape cortical network architecture.

neuroscience↗

bioRxiv2022

Neural circuit-wide analysis of gene expression during deafening-induced destabilization ofbirdsong

Sensory feedback is required for stable execution of learned motor skills, and its loss can severely disrupt motor performance. The neural mechanisms that mediate sensorimotor stability have been extensively studied at systems and physiological levels, yet relatively little is known about how disruptions to sensory input alter the molecular properties of associated motor systems. Songbird courtship song, a model for skilled behavior, is a learned and highly structured vocalization that is destabilized following deafening. Here, we sought to determine how the loss of auditory feedback modifies gene expression and its coordination across the birdsong sensorimotor circuit. To facilitate this system-wide analysis of transcriptional responses, we developed a gene expression profiling approach that enables the construction of hundreds of spatially-defined RNA-sequencing libraries. Using this method, we found that deafening preferentially alters gene expression across birdsong neural circuitry relative to surrounding areas, particularly in premotor and striatal regions. Genes with altered expression are associated with synaptic transmission, neuronal spines, and neuromodulation and show a bias toward expression in glutamatergic neurons and Pvalb/Sst-class GABAergic interneurons. We also found that connected song regions exhibit correlations in gene expression that were reduced in deafened birds relative to hearing birds, suggesting that song destabilization alters the inter-region coordination of transcriptional state. Finally, lesioning LMAN, a forebrain afferent of RA required for deafening-induced song plasticity, had the largest effect on groups of genes that were also most affected by deafening. Combined, this integrated transcriptomics analysis demonstrates that the loss of peripheral sensory input drives a distributed gene expression response throughout associated sensorimotor neural circuitry and identifies specific candidate molecular and cellular mechanisms that support stability and plasticity of learned motor skills.

neuroscience↗

bioRxiv2021

Heritable differences in synaptic zinc-transporter levels drive variation in learned birdsong

The authors have withdrawn this manuscript. During revision of our manuscript, we carried out several lines of additional experiments and analyses that failed to fully support and reproduce the results previously presented in Figure 4 (regarding potential mechanisms whereby zinc and SLC39all contribute to song tempo). We therefore do not want this result to be cited and are withdrawing our paper while we carry out additional experiments to clarify potential contributions of SLC39all to individual variation in song tempo. We apologize for any inconvenience caused to our readers. Any questions can be addressed to DGM (first/corresponding author) and/or MSB (last/senior author).

neuroscience↗