Cellular/Molecular
Ephrin Signaling in Astrocytes
Michael W. Nestor, Lee-Peng Mok, Mohan E. Tulapurkar, and Scott M. Thompson
(see pages 12817–12828)
Neuronal-glial interactions are increasingly recognized as two-way conversations. This week, Nestor et al. listened in on ephrin signaling between neurons and glia. The ephrinA4 receptor (EphA4R) tyrosine kinase and its ligand ephrinA3 are expressed in hippocampus. In cultured mouse hippocampal slices, astrocytes identified by green fluorescent protein, regularly extended and retracted filopodia-like processes. Within minutes of application, exogenous ephrinA3 doubled the length of these filopodia and increased process outgrowth. Phosphatidylinositol-specific phospholipase-C cleaved the glycosylphosphatidylinositol linkage, thus setting free endogenous ephrins, which then replicated the effect of exogenous ephrin. The astrocytes expressed multiple EphRs and were immunopositive for EphA4R. Expression of a dominant-negative kinase dead EphA4R prevented the action of ephrins on astrocytic processes, indicating that ephrins acted on glial membranes. The ephrin-mediated extension of astrocytic filopodia and the previously described ephrin-induced dendritic spine retraction, suggests that glial and neurons may not only be talking, but also dancing.
Development/Plasticity/Repair
Ascl1-Defined Progenitors
Euiseok J. Kim, Cheuk T. Leung, Randall R. Reed, and Jane E. Johnson
(see pages 12764–12774)
Previous studies of the helix loop helix transcription factor, Ascl1 (or Mash 1), indicate that it functions as a neuronal differentiation control factor. This week, Kim et al. considered the role of Ascl1 in the adult. The authors examined two regions that continue to generate new neurons in the adult brain. In mice, Ascl1 was expressed in the dentate gyrus and in the subventricular zone (SVZ). The authors inserted green fluorescent protein (GFP) into the Ascl1 locus to track cells that expressed Ascl1. In the hippocampus, GFP colocalized with BLBP and Sox2, markers of type-2a progenitor cells that ultimately matured into granule cells. In the SVZ and along the rostral migratory stream, GFP cells colabeled with markers of rapidly dividing transit cells. Within 30 days, these labeled cells had migrated to the olfactory bulb and become neurons. Ascl1 also was expressed in the oligodendrocyte but not astrocyte cell lineage.
Behavioral/Systems/Cognitive
The Perception of Motion and Human Middle Temporal Area
John T. Serences and Geoffrey M. Boynton
(see pages 12893–12899)
Subjects were presented with random dot patterns to examine motion detection in the visual pathways. In this example the motion of the dots was 100% coherent. See the article by Serences and Boynton for details.
Based on single unit recordings in nonhuman primates, middle temporal (MT) area has long been considered as central to the perception of motion. But evidence from functional magnetic resonance imaging and multivoxel pattern analysis seems to have rocked that boat, in that visual areas V1–V4 in humans also are direction-sensitive. Serences and Boynton tried to reconcile the distributed versus centralized models by separating conscious perception from neuronal activity. Subjects were presented with random dot motion patterns in either unambiguous motion trials, in which dots moved in a coherent direction, or ambiguous motion trials, in which dots moved randomly. They were then asked to report the direction of perceived motion. In unambiguous trials, V1–V4 and the human MT complex (hMT+) all appeared to encode directional information, whereas ambiguous trials relied on hMT+ and somewhat on V3a. Alas, when the conscious component of perception was dissociated from motion perception, hMT+ remained the primary motion detector.
Neurobiology of Disease
Toll-Like Receptor 3 and Growth Cones
Jill S. Cameron, Lena Alexopoulou, Jacob A. Sloane, Allitia B. DiBernardo, Yinghua Ma, Bela Kosaras, Richard Flavell, Stephen M. Strittmatter, Joseph Volpe, Richard Sidman, and Timothy Vartanian
(see pages 13033–13041)
With injury or infection, pathogen- and host-derived molecules can inhibit the regrowth of axons. This week, Cameron et al. provide support for the “danger” theory in which the immune system distinguishes between health and injury, rather than between self and nonself. Toll-like receptors (TLR) are thought to act in such “danger” signaling. TLRs can be activated by viral double-stranded RNA or by host messenger RNA. The authors report that the TLR3 agonist poly I:C, a double-stranded RNA, inhibited neurite outgrowth in explants of embryonic chick dorsal root ganglia (DRG) neurons. A mammalian brain-derived mRNA had a similar effect. Acute treatment with poly I:C rapidly collapsed neuronal growth cones, an effect that was intrinsic to neurons and independent of immune cell activation or gene transcription. Mice injected with poly I:C in vivo had fewer DRG axons and compromised sensorimotor function.
