Animals across various phyla exhibit odor-evoked innate attraction behavior that is developmentally programmed. The mechanism underlying such behavior remains unclear because the odorants that elicit robust attraction responses and the neuronal circuits that mediate this behavior have not been identified. Here, we describe a functionally segregated population of olfactory sensory neurons (OSNs) and projection neurons (PNs) in Drosophila melanogaster that are highly specific to ammonia and amines, which act as potent attractants. The OSNs express IR92a, a member of the chemosensory ionotropic receptor (IR) family and project to a pair of glomeruli in the antennal lobe, termed VM1. In vivo calcium-imaging experiments showed that the OSNs and PNs innervating VM1 were activated by ammonia and amines but not by nonamine odorants. Flies in which the IR92a + neurons or IR92a gene was inactivated had impaired amine-evoked physiological and behavioral responses. Tracing neuronal pathways to higher brain centers showed that VM1-PN axonal projections within the lateral horn are topographically segregated from those of V-PN and DC4-PN, which mediate innate avoidance behavior to carbon dioxide and acidity, respectively, suggesting that these sensory stimuli of opposing valence are represented in spatially distinct neuroanatomic loci within the lateral horn. These experiments identified the neurons and their cognate receptor for amine detection, and mapped amine attractive olfactory inputs to higher brain centers. This labeled-line mode of amine coding appears to be hardwired to attraction behavior.olfaction | neural circuit | odorant receptor T he olfactory system of adult Drosophila melanogaster serves as a genetically and anatomically simple model for studying how sensory input is translated into behavior output. The majority of olfactory sensory neurons (OSNs) express one functional receptor that is composed of an odorant receptor coreceptor (ORCO) and one of ∼45 odorant receptors (ORs) (1-3). About a quarter of the OSNs that do not express ORs recently were shown to express a second family of insect olfactory receptors termed the "ionotropic receptors" (IRs) (4). Each of these OSN types expresses a single or multiple IRs together with a coreceptor, IR8a or IR25a (or rarely both) (5). OR and IR sensory neurons expressing the same receptor send their axonal projections to one or rarely two of ∼50 spatially invariant glomeruli within the antennal lobe (AL) (4, 6-8) where they provide significant synaptic inputs to second-order projection neurons (PNs) that convey the sensory information to higher brain centers such as the mushroom body (MB) and the lateral horn (LH) (9-12).This genetic and anatomical simplicity of Drosophila has allowed us to further our understanding of a general principle of innate behavior. The emerging characteristics of a neural circuit that is hardwired to a specific behavior include (i) the specificity of the sensory neurons to a single chemical cue and (ii) the discrete spatial representation of tha...

Glioblastoma remains the most common and devastating primary brain tumor despite maximal therapy with surgery, chemotherapy, and radiation. The glioma stem cell (GSC) subpopulation has been identified in glioblastoma and likely plays a key role in resistance of these tumors to conventional therapies as well as recurrent disease. GSCs are capable of self-renewal and differentiation; glioblastoma-derived GSCs are capable of de novo tumor formation when implanted in xenograft models. Further, GSCs possess unique surface markers, modulate characteristic signaling pathways to promote tumorigenesis, and play key roles in glioma vascular formation. These features, in addition to microenvironmental factors, present possible targets for specifically directing therapy against the GSC population within glioblastoma. In this review, the authors summarize the current knowledge of GSC biology and function and the role of GSCs in new vascular formation within glioblastoma and discuss potential therapeutic approaches to target GSCs.