Biology subjects

Frazel, P.

Publications and source records attributed to Frazel, P..

4 recordsLinked to original sources

bioRxiv2025

Mechanisms and control of a novel vocalization: the singing mouse song is a whistle that depends on air sac inflation

Identifying variation in vocal morphology and sound production mechanisms is essential to understanding vocal diversity. Rodents provide an ideal system for exploring this variation as they use multiple sound production mechanisms and have novel vocal structures whose morphology varies interspecifically. Here, we describe the laryngeal morphology and identify the sound production mechanism of Alstons singing mouse (Scotinomys teguina), which produce stereotyped songs. We used micro-computed tomography to examine laryngeal morphology and manipulated excised larynges and surgically ablated a laryngeal muscle to determine sound production mechanism and frequency control. Laryngeal manipulations indicated that a whistle mechanism, likely an edge tone or shallow cavity, produces song. Singing mouse whistles are unique compared to other rodents because they rely on the inflation of an enlarged intralaryngeal air sac called the ventral pouch. Whistle frequency can be controlled by ventral pouch inflation, laryngeal airflow, and by cricothyroid muscle action. Cricothyroid ablation inhibited frequency modulation in vivo, suggesting that singing mice use this muscle during singing. Singing mouse laryngeal morphology and vocal mechanism are distinct from other Neotomids; instead of using vocal fold oscillations for loud, long-distance calls and whistles for close-range interactions, singing mice appear to use whistles for distant and close exchanges by inflating their intralaryngeal air sac. Air sacs have evolved repeatedly among vocalizing mammals and our results indicate a new role for these structures in generating sound. Together, our results expand on an emerging story of how biomechanic and morphological variation contributes to vocal diversity.

physiology↗

bioRxiv2023

Single-cell analysis of the nervous system at small and large scales with instant partitions

Single-cell RNA sequencing is a new frontier across all biology, particularly in neuroscience. While powerful for answering numerous neuroscience questions, limitations in sample input size, and initial capital outlay can exclude some researchers from its application. Here, we tested a recently introduced method for scRNAseq across diverse scales and neuroscience experiments. We benchmarked against a major current scRNAseq technology and found that PIPseq performed similarly, in line with earlier benchmarking data. Across dozens of samples, PIPseq recovered many brain cell types at small and large scales (1,000-100,000 cells/sample) and was able to detect differentially expressed genes in an inflammation paradigm. Similarly, PIPseq could detect expected and new differentially expressed genes in a brain single cell suspension from a knockout mouse model; it could also detect rare, virally-la-belled cells following lentiviral targeting and gene knockdown. Finally, we used PIPseq to investigate gene expression in a nontraditional model species, the little skate (Leucoraja erinacea). In total, PIPSeq was able to detect single-cell gene expression changes across models and species, with an added benefit of large scale capture and sequencing of each sample.

neuroscience↗

bioRxiv2022

Determinants of Motor Neuron Functional Subtypes Important for Locomotor Speed

Locomotion requires precise control of the strength and speed of muscle contraction and is achieved by recruiting functionally-distinct subtypes of motor neurons (MNs). MNs are essential to movement and differentially susceptible in disease, but little is known about how MNs acquire functional subtype-specific features during development. Using single-cell RNA profiling in embryonic and larval zebrafish, we identify novel and conserved molecular signatures for MN functional subtypes, and identify genes expressed in both early post-mitotic and mature MNs. Assessing MN development in genetic mutants, we define a molecular program essential for MN functional subtype specification. Two evolutionarily-conserved transcription factors, Prdm16 and Mecom, are both functional subtype-specific determinants integral for fast MN development. Loss of prdm16 or mecom causes fast MNs to develop transcriptional profiles and innervation similar to slow MNs. These results reveal the molecular diversity of vertebrate axial MNs and demonstrate that functional subtypes are specified through intrinsic transcriptional codes.

neuroscience↗

bioRxiv2021

Early stage differentiation of glia in human and mice.

Macroglia (astrocytes and oligodendrocytes) are required for normal development and function of the central nervous system, yet many questions remain about their emergence in the brain and spinal cord. Here we used single-cell RNA sequencing (scRNAseq) to analyze over 298,000 cells and nuclei during macroglia differentiation from mouse embryonic and human induced pluripotent stem cells. We computationally identify candidate genes involved in fate specification of glia in both species, and report heterogeneous expression of astrocyte surface markers across differentiating cells. We then used our scRNAseq data to optimize a previous mouse astrocyte differentiation protocol, decreasing the overall protocol length and complexity. Finally, we used multiomic, dual single nuclei (sn)RNAseq/snATACseq analysis to uncover potential genomic regulatory sites mediating glial differentiation. These datasets enable future optimization of glial differentiation protocols and provide insight into human glial differentiation.

neuroscience↗