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FRIMEDBIO-Fri prosj.st. med.,helse,biol

Unlocking molecular diversity in the brain-to-body gateway: spatial transcriptomics and proteomics of brainstem-to-spinal cord projections

Alternative title: Molekylær mangfold i portalen fra hjernen til kroppen: Spatiell transkriptomikk og proteomikk av hjernestamme-ryggmargsprojeksjoner

Awarded: NOK 9.6 mill.

Packed with an intricate assembly of neurons and circuits serving vital functions (motor, respiratory, cardiovascular, hormonal regulation, temperature and pain regulation, sleep) the brainstem is the LEAST expendable part of the brain. These multiple, critical functions are mediated by a large population of brainstem-to-spinal cord neurons. Functional disorders and diseases linked to these neurons are numerous, with diverse causes, such as genetic mutations, strokes (10-15% occur in the brainstem), multiple sclerosis, congenital defects, tumors, and spinal cord injuries. Despite their essential role in critical body functions and a broad spectrum of disease states, knowledge about the brainstem-to-spinal cord neurons is remarkably limited. We know where they are located, and that they exhibit stereotypic clustering in the brainstem. But many central questions remain unanswered: How many distinct neuron groups exist? Are functions group-specific or more diffusely distributed? How are different neuron groups patterned genetically and developmentally? How do their axons terminate in the spinal cord and mediate function? The main reason for this knowledge gap is that we lack a comprehensive molecular characterization of brainstem-to-spinal cord neurons - a huge bottleneck in understanding motor and autonomic control, and in developing more precise tools for experimental manipulation. We test here the hypothesis that brainstem-to-spinal cord neurons can be functionally identified by unique molecular signatures, which we will use to leverage unprecedented mapping and experimental manipulation of this complex and poorly understood gateway from brain to body. Our comprehensive molecular characterization will provide new avenues for exploring development, disease mechanisms, gene linkage and potential therapeutics, allowing us to obtain deep insight into the function of the brainstem-to-spinal cord neurons in health and disease.

Packed with an intricate assembly of neurons and circuits serving vital functions (motor, respiratory, cardiovascular, endocrine and exocrine control, temperature and pain regulation, sleep) the brainstem is the LEAST expendable part of the brain. These critical functions are mediated by a large population of brainstem-to-spinal cord neurons. Functional disorders linked to these neurons are numerous, with diverse causes: genetic mutations, strokes (10-15% occur in the brainstem), multiple sclerosis, congenital defects, tumors, spinal cord injuries. Given their essential functions, we test here the hypothesis that brainstem-to-spinal cord neurons can be functionally identified by unique molecular signatures, which we will use to leverage unprecedented mapping and experimental manipulation of this complex and poorly understood gateway from brain to body, thereby obtaining deep insight into their function in health and disease. Despite their essential role in critical body functions and a broad spectrum of disease states, knowledge about the brainstem-to-spinal cord neurons is remarkably limited. We know where they are located, and that they exhibit stereotypic clustering in the brainstem. But many central questions remain unanswered: How many distinct neuron groups exist? Are functions group-specific or more diffusely distributed? How are different neuron groups patterned genetically and developmentally? How do their axons terminate in the spinal cord and mediate function? The main reason for this knowledge gap is that we lack a comprehensive molecular characterization of brainstem-to-spinal cord neurons - a huge bottleneck in understanding motor and autonomic control, and in developing more precise tools for experimental manipulation. A comprehensive molecular characterization of brainstem-to-spinal cord neuron diversity will provide new avenues for exploring disease mechanisms, gene linkage and potential therapeutics.

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FRIMEDBIO-Fri prosj.st. med.,helse,biol

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