Sensory and respiratory brainstem circuits: from molecular diversity and connectivity to function

• Applicants: Dr. Luis R. Hernandez-Miranda, Ph.D.; Professor Dr. Hans-Gerd Nothwang
• Subject Area: Developmental Neurobiology ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 514060831

The mammalian brainstem harbors an enormous diversity of neuronal circuits that process multiple modalities of sensory information and the control of vital functions that maintain homeostasis. The extent of this diversity and how it contributes to individual functional circuits is largely unknown. Understanding brainstem circuits requires the parallel delineation of the molecular identities and functional traits of their distinct elements. Here, we will use single-cell transcriptomic profiling to uncover the molecular diversity of neurons emerging from four defined brainstem progenitor domains. The selected domains simultaneously generate essential neurons serving in the processing of auditory signals and in the control of respiration. This focus will be fully exploited by the high-profile synergistic network of the two applicants, Prof. Dr. H.G. Nothwang (auditory system specialist) and Dr. L. R. Hernandez-Miranda (respiratory system specialist) with regards to research expertise and resources, especially mouse lines. To define the neuronal diversity generated from the selected progenitor domains, we will use intersectional genetic labeling in single-cell RNA-sequencing (scRNA-seq) experiments. Bioinformatics will establish the molecular identities of the neurons derived from the chosen domains, with a particular focus on auditory and respiratory neurons. The information generated from these analyses will then be used to map their connections and to functionally interrogate their precise role in auditory processing and the control of respiration. The expected results of this project will: i) generate fundamental information on brainstem auditory and respiratory neuron diversity and its associated connectivity, ii) advance our understanding on essential sensory and homeostatic functional circuits, iii) provide a rich and unique resource for neuroscientists, physiologists, clinicians and biomedical researchers aiming at the identification of the genetic and molecular basis of brainstem disorders.

• DFG Programme: Research Grants