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Molecular and functional profiling of cell diversity and identity in the lateral superior olive, an auditory brainstem center with ascending and descending projections

ABSTRACT: Molecular and functional profiling of cell diversity and identity in the lateral superior olive, an auditory brainstem center with ascending and descending projections

PROVIDER: PRJNA1009815 | ENA |

REPOSITORIES: ENA

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Molecular and functional profiling of cell diversity and identity in the lateral superior olive, an auditory brainstem center with ascending and descending projections

Project description:The lateral superior olive (LSO), a conspicuous integration center in the auditory brainstem, contains a remarkably heterogeneous neuron population. Ascending neurons, predominantly principal neurons (pLSOs), process interaural level differences for sound localization. Descending neurons (lateral olivocochlear neurons, LOCs) provide feedback into the cochlea and likely protect from acoustic overexposure. The molecular determinants of the neuronal diversity in the LSO are largely unknown. Here, we employed patch-seq analysis in juvenile mice to classify LSO neurons by their functional and molecular profiles, including developmental aspects. Across the sample (n=86), genes involved in ATPsynthesis were particularly highly expressed, confirming the energy expenditure of auditory neurons. Two clusters were identified, pLSOs and LOCs. They were distinguishable by 353 differentially expressed genes (DEGs), most being novel for the LSO. Electrophysiological analysis corroborated the transcriptomic clustering. We focused on genes impacting neuronal input-output properties and validated some by immunohistochemistry, electrophysiology, and pharmacology. These genes encode proteins like osteopontin, Kv11.3, and Kvb3 (pLSO-specific), calcitonin-gene-related peptide (LOC-specific), or Kv7.2 and Kv7.3 (no DEGs). We identified 12 ‘Super DEGs’ and 12 genes demonstrating ‘Cluster similarity’. Collectively, we provide fundamental and comprehensive insights into the molecular composition of individual ascending and descending neurons in the juvenile auditory brainstem and how this may relate to their specific functions, including developmental aspects.

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β-aminopropionitrile Induces Distinct Pathologies in the Ascending and Descending Thoracic Aortic Regions of Young Mice

Project description:The purpose of this study was to determine whether lysyl oxidase inhibition using β-aminopropionitrile (BAPN) induced region-specific aortopathies in mice. The effects of BAPN were first characterized with regard to dose, strain, age, and sex. Subsequently, BAPN was administered to young male C57BL/6J mice. BAPN-induced aortic rupture predominantly occured or originated in the descending thoracic aorta. For mice surviving 12 weeks of BAPN administration, profound dilatation was consistently observed in the ascending region, while relatively sporadic in the descending thoracic region. Pathological features were distinct between the ascending and descending thoracic regions. Aortic pathology in the ascending region was characterized by luminal dilatation and elastic fiber disruption throughout the media. The descending thoracic region frequently had dissection with false lumen formation, macrophage infiltration, collagen deposition, and remodeling of the media and adventitia. Cells surrounding the false lumen were predominantly positive for α-smooth muscle actin. To investigate the molecular basis of the regional heterogeneity, ascending and descending thoracic aortas were harvested after one week of BAPN administration prior to the appearance of overt pathology. BAPN compromised contractile properties in both regions equivalently, while RNA sequencing demonstrated that BAPN altered transcriptomes related to extracellular matrix and cell division differentially between the two regions. In conclusion, BAPN-induced pathologies show distinct, heterogeneous features within and between ascending and descending aortic regions in young mice.

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Project description:β-aminopropionitrile Induces Distinct Pathologies in the Ascending and Descending Thoracic Aortic Regions of Young Mice

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Gene expression data for three mouse auditory brainstem nuclei at two times of development

Project description:Genome-wide gene expression was obtained in three auditory brainstem nuclei (defined below), at two different ages in mice, postnatal day (P)3 and P14. The primary aim was to identify genes which are differentially expressed between the medial nucleus of the trapezoid body (MNTB) and the superior olive (LSO), at both age groups.

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