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Developmental origins of ventral medullary NK1r neurons

Gray PA, Vandunk C (2007) Developmental origins of ventral medullary NK1r neurons. Neuroscience 2007 Abstracts 187.15/SS7. Society for Neuroscience, San Diego, CA.

Summary: Breathing is a fundamental neural behavior generated by neurons within the brainstem. In the adult rat, bilateral injection of substance P conjugated to saporin (SSP) in the preBötzinger Complex (preBötC) eliminates normal breathing. Unilateral injection produces sleep disordered breathing and eliminates the effects of excitatory amino acid injection on breathing and blood pressure. SSP injection in the RTN region, in contrast, blunts chemosensitivity. The extent these different effects are due to ablation of anatomically, functionally, or genetically distinct populations are unknown. Further, the extent NK1R expression identifies unique populations in neonatal mice is unknown. Transcription factors are fundamental to determining the properties of neurons and it has been proposed a “combinatorial code” of transcription factor expression defines each distinct functional population. From a genome-scale analysis of over 1000 transcription factors and transcriptional co-factors we identified several genes expressed in respiratory regions of the brainstem. Using immunohistochemistry, we analyzed gene expression patterns of NK1R expressing neurons of the ventral medulla in embryonic and neonatal mice. We find there are at least four genetically distinct, partially overlapping populations of NK1R expressing neurons in the ventral medulla. These differ in the transcription factors they express, their onset of NK1R expression, and their co-expression of peptides and g-protein coupled receptors. At the level of the preBötC, there are two populations of NK1R expressing neurons derived from distinct developmental progenitor populations. One population corresponds to the preBötC as defined in rats and co-expresses the peptide somatostatin. A second population is continuous with, and genetically identical to the subCVLM population important for respiratory-cardiovascular coordination. Both populations co-express the somatostatin 2a receptor (SST2aR). At the level of the RTN/pFRG, there are also two populations of NK1R expressing neurons that are derived from similar developmental precursors as the preBötC. Neither of these populations expresses SST2aR. Whether either of these populations corresponds to the RTN or pFRG is currently unknown. These data suggest both the preBötC and RTN/pFRG regions contain developmentally related NK1R expressing populations. Further, they identify the developmental origin of preBötC neurons known to be essential for normal breathing and provide a foundation for understanding the genetic origin of an important neural circuit.

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